| 1. |
- Jensen, Poul Erik H., et al.
(författare)
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Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis : Results from the ABIRISK prospective cohort study
- 2019
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 326, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-β) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-β-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-β ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.
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| 2. |
- Bernhard, Michael, et al.
(författare)
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The Varieties of Democracy Core Civil Society Index
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This paper introduces the Core Civil Society Index (CCSI), a measure of the robustness of civil society, using indicators from the Varieties of Democracy battery on civil society. It begins with a discussion of the reemergence of civil society as a central concept in comparative politics and discusses the existing state of data to capture it. It then discusses the conceptualization behind the CCSI and the construction of the measure. This is followed by a series of face and discriminant validity checks. The paper closes with an example of the CCSI’s utility by examining the question of whether postcommunist civil society is “weak” compared to other regions. We find no evidence that postcommunist civil society is less robust than civil society in other major world regions via time - series cross - sectional analysis using 2999 country - year observations between 1989 and 2012.
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| 3. |
- Beyder, Arthur, et al.
(författare)
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Loss-of-Function of the Voltage-Gated Sodium Channel Na(V)1.5 (Channelopathies) in Patients With Irritable Bowel Syndrome
- 2014
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 146:7, s. 1659-1668
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: SCN5A encodes the a-subunit of the voltage-gated sodium channel Na(V)1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Na(V)1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted Na(V)1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-Na(V)1.5 had the greatest effect in reducing Na(V)1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na(V)1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.
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| 4. |
- Beyder, Arthur, et al.
(författare)
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Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome.
- 2014
-
Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 146:7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5.METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls.RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS.CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt NaV1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.
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| 5. |
- Bizzarro, Fernando, et al.
(författare)
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Party Strength and Economic Growth
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- While a large literature suggests an important role for political parties in economic development, this is the first attempt to lay out a comprehensive theory and a reasonably comprehensive empirical test of the proposition. We argue that strong parties broaden the constituencies to which policy makers respond and help politicians solve coordination problems. These features help ensure better economic management, public services, and political stability. And this, in turn, enhances economic growth. Drawing on a novel measure of party strength from the Varieties of Democracy dataset, we test this theory on data drawn from more than 150 countries, observed annually from 1900–2012. We identify a sizeable effect which is robust to various specifications, estimators, and samples. The effect operates in both democracies and autocracies and is fairly stable across regions and time periods. We also find provisional evidence in favor of causal mechanisms pertaining to public services and political stability.
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| 6. |
- Bizzarro, Fernando, et al.
(författare)
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Party Strength and Economic Growth
- 2018
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Ingår i: World Politics. - 0043-8871 .- 1086-3338. ; 70:2, s. 275-320
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Tidskriftsartikel (refereegranskat)abstract
- © Trustees of Princeton University 2018. While a large literature suggests an important role for political parties in development, this article is the first attempt to layout and test a comprehensive theory connecting parties to economic growth. The authors argue that strong parties broaden the constituencies to which policymakers respond and help politicians solve coordination problems. These features help to ensure better economic management, public services, and political stability. And this, in turn, enhances economic growth. Drawing on a novel measure of party strength from the Varieties of Democracy data set, the authors test this theory on data drawn from more than 150 countries observed annually from 1901-2010. They identify a sizeable effect that is robust to various specifications, estimators, and samples. The effect operates in both democracies and autocracies, and is fairly stable across regions and time periods.
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| 7. |
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| 8. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 9. |
- Hedberg, Jakob, et al.
(författare)
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Randomized controlled trial of nasogastric tube use after esophagectomy : study protocol for the kinetic trial
- 2024
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Ingår i: Diseases of the esophagus. - : John Wiley & Sons. - 1120-8694 .- 1442-2050. ; 37:6
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Tidskriftsartikel (refereegranskat)abstract
- Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.
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| 10. |
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| 11. |
- Katsaounou, Paraskevi, et al.
(författare)
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Smoking and severe persistent asthma
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Smoking has detrimental effects on different clinical aspects of asthma, like accelerated decline in lung function, diminished symptom control, worse quality of life(QoL) and impaired therapeutic response. Fighting for Breath, a survey conducted by EFA(2005) showed that a worrying number of uncontrolled asthmatic patients(pts) indicated exposure to passive smoking as possible reason for poor QoL. After a decade, we conducted Still Fighting for Breath(GfK on behalf of Novartis upon EFA's invitation), an online survey in 1333 pts with severe persistent asthma(SPA) to assess the impact of SPA on pts’ daily life(fig1). Though law banning smoking in public spaces is implemented, still a high proportion of pts(88%) reported disruption in activities of daily living with 38% presenting poor perception of their disease control(disconnect b/w Pts perception and GINA assessment). Asthmatics identified exposure to smoking as trigger for exacerbations, with 63% of them(68% of caregivers) avoiding smoky premises. Percentage of smokers with SPA was higher than the general population in some of the countries. Current smokers with asthma were significantly more frequently diagnosed with anxiety(47%) and depression (41%) than never-smokers(40% and 27%, resp.) and ex-smokers(42% and 28%, resp.)(z-test, Α = 0.05). Thus, there is a need for improved management and support(smoking cessation, treatment, assessment of perception and psychological conditions) of asthmatic smokers with SPA.
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| 12. |
- Marquardt, Kyle L., 1983, et al.
(författare)
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Experts, Coders, and Crowds:An analysis of substitutability
- 2017
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Recent work suggests that crowd workers can replace experts and trained coders in common coding tasks. However, while many political science applications require coders to both and relevant information and provide judgment, current studies focus on a limited domain in which experts provide text for crowd workers to code. To address potential over-generalization, we introduce a typology of data producing actors - experts, coders, and crowds - and hypothesize factors which affect crowd-expert substitutability. We use this typology to guide a comparison of data from crowdsourced and expert surveys. Our results provide sharp scope conditions for the substitutability of crowd workers: when coding tasks require contextual and conceptual knowledge, crowds produce substantively dierent data from coders and experts. We also find that crowd workers can cost more than experts in the context of cross-national panels, and that one purported advantage of crowdsourcing - replicability - is undercut by an insucient number of crowd workers.
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| 13. |
- Olivecrona, Gunilla, et al.
(författare)
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Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia
- 2010
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Ingår i: Journal of Lipid Research. - New York : Rockefeller U.P.. - 0022-2275 .- 1539-7262. ; 51:6, s. 1535-1545
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Tidskriftsartikel (refereegranskat)abstract
- We investigated a family from northern Sweden in which three of four siblings have congenital chylomicronemia. Lipoprotein lipase (LPL) activity and mass in pre- and post-heparin plasma were low, and LPL release into plasma after heparin injection was delayed. LPL activity and mass in adipose tissue biopsies appeared normal. [35S]Methionine incorporation studies on adipose tissue showed that newly synthesized LPL was normal in size and normally glycosylated. Breast milk from the affected female subjects contained normal to elevated LPL mass and activity levels. The milk had a lower than normal milk lipid content, and the fatty acid composition was compatible with the milk lipids being derived from de novo lipogenesis, rather than from the plasma lipoproteins. Given the delayed release of LPL into the plasma after heparin, we suspected that the chylomicronemia might be caused by mutations in GPIHBP1. Indeed, all three affected siblings were compound heterozygotes for missense mutations involving highly conserved cysteines in the Ly6 domain of GPIHBP1 (C65S and C68G). The mutant GPIHBP1 proteins reached the surface of transfected CHO cells but were defective in their ability to bind LPL (as judged by both cell-based and cell-free LPL binding assays). Thus, the conserved cysteines in the Ly6 domain are crucial for GPIHBP1 function.
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| 14. |
- Thunström, Erik, 1980, et al.
(författare)
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Increased Inflammatory Activity in Nonobese Patients With Coronary Artery Disease and Obstructive Sleep Apnea
- 2015
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 38:3, s. 463-71
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD). Enhanced vascular inflammation is implicated as a pathophysiologic mechanism but obesity is confounding. We aimed to address the association of OSA with inflammatory biomarkers in a nonobese cohort of revascularized patients with CAD and preserved left ventricular ejection fraction. Design: Cross-sectional analysis of baseline investigations of a randomized controlled trial. Setting: Clinic-based. Participants: There were 303 nonobese patients with CAD, of whom 213 with OSA (apnea-hypopnea index [AHI] >/=15 events/h) and 90 without OSA (AHI < 5 events/h). Obese patients with CAD and OSA (N = 105) were chosen as an additional control group. Interventions: None. Measurements: Circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha were assessed in relation to OSA diagnosis based on AHI >/= 15 events/h as well as oxygen desaturation index (ODI) >/= 5 events/h. Results: Nonobese patients with OSA had significantly higher levels of hs-CRP and IL-6 than those without OSA. The values did not differ significantly between obese and nonobese patients with OSA. In bivariate regression analysis, AHI >/= 15 events/h was associated with all four biomarkers but not so in the multivariate model after adjustment for confounders. ODI >/= 5 events/h was associated with hs-CRP (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.99) and IL-6 (OR 1.30; 95% CI 1.05-1.60) in multivariate analysis. Conclusions: OSA with ODI >/= 5 was independently associated with increased inflammatory activity in this nonobese CAD cohort. The intermittent hypoxemia, rather than the number of apneas and hypopneas, appears to be primarily associated with enhanced inflammation.
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| 15. |
- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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Design and Synthesis of BACE-1 Inhibitors Containing a New Hydroxyethylene (HE) Scaffold: Potent activities in a cellular assay
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In a preceding report from our group we disclosed the development of a novel HE transition state isostere with a difluorophenoxymethyl side chain in the P1 position and a methoxy group in the P1’ position furnishing highly potent inhibitors of BACE-1 (i.e. lead compound 1), which moreover exhibit very promising selectivity over cathepsin D. In a continuation of this work with the aim at improving on the cell-based activity and pharmacokinetic properties, we have further developed the SAR for the P1 side chain of inhibitor 1 whereby the P1 side chain oxygen has been substituted for an amine, a carbon or a bond. The chemistry developed for the previous HE inhibitor structure 1 has now been extended to readily accommodate the introduction of new P1 side chains into this new HE scaffold. These modifications have given rise to several highly potent inhibitors where the most potent displayed a BACE-1 Ki value of 0.2 nM and a cell-based Aβ40 IC50 value of 9 nM. Thus, regarding the enzyme inhibition in the cell assay a more than 600-fold improvement compared to compound 1 was achieved via minor structural alterations.
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| 16. |
- Alksnis, M., et al.
(författare)
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Use of synthetic oligodeoxyribonucleotides for type-specific identification of coxsackie B viruses
- 1989
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Ingår i: Molecular and Cellular Probes. - : Elsevier BV. - 0890-8508 .- 1096-1194. ; 3:2, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic oligodeoxyribonucleotides were used for type-specific identification of members of the coxsackie B virus group by nucleic acid hybridization. Two pairs of oligonucleotide chains were constructed based on nucleotide sequences in the VP1 regions of coxsackieviruses B3 and B4. Each labelled probe had a length of 24 nucleotides. The results showed that the oligonucleotide hybridized in a type-specific manner when assayed with extracts from cells infected with all different coxsackie B viruses. A method based on similar principles may thus be used for enterovirus typing.
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| 17. |
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| 18. |
- Au, Gough G, et al.
(författare)
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Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21.
- 2005
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 26:6, s. 1471-6
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Tidskriftsartikel (refereegranskat)abstract
- Cultured melanoma cell lines despite exhibiting similar in vitro morphology, display significant phenotypic and growth rate differences when propagated as in vivo xenografts. Previously we have shown that Coxsackievirus A21 (CVA21) lytically infects in vitro cultures of malignant melanoma cells and is efficient at reducing the tumor burden of mice bearing slow-growing SK-Mel-28 melanoma xenografts. The oncolytic activity of CVA21 against in vivo melanoma xenografts, which possess rapid growth rates and more extensive vascular structure than SK-Mel-28 xenografts warrants further investigation. In the present study we evaluated the oncolytic action of CVA21 against rapidly growing melanoma xenografts (ME4405) which exhibit a highly vascular phenotype. Flow cytometric analysis indicated that in vitro cultures of ME4405 cells expressed comparable levels of the CVA21 cellular receptors, ICAM-1 (intercellular adhesion molecules-1) and DAF (decay accelerating factor) to SK-Mel-28 cells. Despite similar levels of CVA21 receptor expression, SK-Mel-28 cells appear to be more susceptible to viral lysis than ME4405 cells, even though the kinetics of virus replication in both lines was comparable. Intratumoral, intraperitoneal or intravenous administration of CVA21 were equally effective in reducing the tumor volume of ME4405 xenografts in immunodeficient mice, and provides further evidence for the use of CVA21 as a novel oncolytic agent against varying phenotypes of malignant melanoma.
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| 19. |
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| 20. |
- Brue, Thierry, et al.
(författare)
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Diabetes in patients with acromegaly treated with pegvisomant : observations from acrostudy
- 2019
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Ingår i: Endocrine. - : SPRINGER. - 1355-008X .- 1559-0100. ; 63:3, s. 563-572
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo explore the effects of pegvisomant (PEGV) on glucose metabolism in patients with acromegaly within ACROSTUDY, an international, observational, prospective safety surveillance study.MethodsPatients were retrospectively divided into two cohorts, with (DM group) or without diabetes mellitus (no-DM). Parameters of glucose metabolism and IGF-I values were analyzed yearly both cross-sectionally for 4 years (yrs) and longitudinally at 1 and 4-5yrs of PEGV treatment.ResultsAmong 1762 patients, 510 (28.9%) had DM before PEGV start. At cross-sectional analyses, in the DM group mean blood glucose was 140.058.7mg/dl at baseline, 116.4 +/- 44.8mg/dl at year 1 and 120.0 +/- 44.3mg/dl at yr 4. Mean HbA1c was 6.6 +/- 1.2 % at yr 1 vs. 7.0 +/- 1.4 % at baseline. HbA1c was above 6.5% in 61.9% at baseline and ranged from 45.4 to 53.8% at subsequent yearly time points. At the 4-yr longitudinal analysis, in the DM group (n=109), mean blood glucose decreased by 20.2mg/dl at yr 4, mean HbA1c was 7.0 +/- 1.5% at baseline vs. 6.8 +/- 1.4%. Patients achieved IGF-I normalization in 52.1% and 57.4% of cases in the DM and no-DM groups, respectively at 1 year. The mean daily PEGV dose (mg/day) was higher in the DM group (18.2 vs. 15.3) while the absolute change of IGF-I values from baseline was similar in both groups. PEGV was well tolerated in both groups without any unexpected AEs.Conclusions p id=Par4 Patients with DM had a moderate decrease in mean fasting glucose values during PEGV treatment.
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| 21. |
- Ceder, Mikaela M., et al.
(författare)
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The Fly Homologue of MFSD11 Is Possibly Linked to Nutrient Homeostasis and Has a Potential Role in Locomotion : A First Characterization of the Atypical Solute Carrier CG18549 in Drosophila Melanogaster
- 2021
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Ingår i: Insects. - : MDPI. - 2075-4450. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Cellular transport and function are dependent on substrate influx and efflux of various compounds. In humans, the largest superfamily of transporters is the SoLute Carriers (SLCs). Many transporters are orphans and little to nothing is known about their expression and/or function, yet they have been assigned to a cluster called atypical SLCs. One of these atypical SLCs is MFSD11. Here we present a first in-depth characterization of the MFSD11, CG18549. By gene expression and behavior analysis on ubiquitous and brain-specific knockdown flies. CG18549 knockdown flies were found to have altered adipokinetic hormone and adipokinteic hormone receptor expression as well as reduced vesicular monoamine transporter expression; to exhibit an altered locomotor behavior, and to have an altered reaction to stress stimuli. Furthermore, the gene expression of CG18549 in the brain was visualized and abundant expression in both the larvae and adult brain was observed, a result that is coherent with the FlyAtlas Anatomy microarray. The exact mechanism behind the observed behaviors is not fully understood, but this study provides new insights into the expression and function of CG18549. Clearly, these results provide a strong example as to why it is vital to fully characterize orphan transporters and through that gain knowledge about the body during normal condition and disease.
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| 22. |
- Coppedge, Michael, et al.
(författare)
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The Methodology of “Varieties of Democracy” (V-Dem)
- 2019
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Ingår i: BMS Bulletin of Sociological Methodology/ Bulletin de Methodologie Sociologique. - : SAGE Publications. - 0759-1063 .- 2070-2779. ; 143, s. 107-133
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Tidskriftsartikel (refereegranskat)abstract
- This article describes and discusses the new generation of methodological responses to measuring democracy and related issues generated by Varieties of Democracy (V-Dem). V-Dem is distinct in several regards in addition to its unique level of disaggregation, by the combination of: historical data extending back to 1900 and for a large selection among them to 1789 for many countries in the world; use of multiple, independent coders for each evaluative question; inter-coder reliability tests incorporated into a custom designed Bayesian item-response theory measurement model; provision of confidence bounds for all point estimates associated with expert-coded questions as well as for all indices; multiple indices reflecting varying theories of democracy; fully transparent aggregation procedures; and that all data are made freely available, including original coder-level judgments (exclusive of any personal identifying information).
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| 23. |
- Coppedge, Michael, et al.
(författare)
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V-Dem Comparisons and Contrasts with Other Measurement Projects
- 2017
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- For policymakers, activists, academics, and citizens around the world the conceptualization and measurement of democracy matters. The needs of democracy promoters and social scientists are convergent. We all need better ways to measure democracy. In the first section of this document we critically review the field of democracy indices. It is important to emphasize that problems identified with extant indices are not easily solved, and some of the issues we raise vis-à-vis other projects might also be raised in the context of the V-Dem project. Measuring an abstract and contested concept such as democracy is hard and some problems of conceptualization and measurement may never be solved definitively. In the second section we discuss in general terms how the Varieties of Democracy (V-Dem) project differs from extant indices and how the novel approach taken by V-Dem might assist the work of activists, professionals, and scholars.
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| 24. |
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| 25. |
- Coppedge, Michael, et al.
(författare)
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Varieties of Democratic Diffusion: Colonial Networks
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- “No man is an island; some countries are, but even so, no country can be regarded as completely self-determined and unaffected by the world beyond its borders” (Coppedge 2012, 301). This is a widely accepted proposition backed by many empirical studies. Yet stating that countries are in some way affected by external forces only hints at the innumerable possible pathways of influence, which have only begun to be explored. This paper builds on Brinks and Coppedge (2006), which reported that geographic neighbors tend to converge toward a shared level of democracy. Here we look at a completely distinct set of networks: that linking colonies and occupied states to their colonizers or occupiers. We find that convergence in levels of liberal democracy is also the dominant tendency in colonial networks when diffusion relationships are properly specified.
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| 26. |
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| 27. |
- Creignou, Maria, et al.
(författare)
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Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes
- 2024
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796.
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Tidskriftsartikel (refereegranskat)abstract
- Background The Molecular International Prognostic Scoring System (IPSS-M) is the new gold standard for diagnostic outcome prediction in patients with myelodysplastic syndromes (MDS). This study was designed to assess the additive prognostic impact of dynamic transfusion parameters during early follow-up. Methods We retrieved complete transfusion data from 677 adult Swedish MDS patients included in the IPSS-M cohort. Time-dependent erythrocyte transfusion dependency (E-TD) was added to IPSS-M features and analyzed regarding overall survival and leukemic transformation (acute myeloid leukemia). A multistate Markov model was applied to assess the prognostic value of early changes in transfusion patterns. Results Specific clinical and genetic features were predicted for diagnostic and time-dependent transfusion patterns. Importantly, transfusion state both at diagnosis and within the first year strongly predicts outcomes in both lower (LR) and higher-risk (HR) MDSs. In multivariable analysis, 8-month landmark E-TD predicted shorter survival independently of IPSS-M (p < 0.001). A predictive model based on IPSS-M and 8-month landmark E-TD performed significantly better than a model including only IPSS-M. Similar trends were observed in an independent validation cohort (n = 218). Early transfusion patterns impacted both future transfusion requirements and outcomes in a multistate Markov model. Conclusion The transfusion requirement is a robust and available clinical parameter incorporating the effects of first-line management. In MDS, it provides dynamic risk information independently of diagnostic IPSS-M and, in particular, clinical guidance to LR MDS patients eligible for potentially curative therapeutic intervention.
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| 28. |
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| 29. |
- Davide, Giacalone, et al.
(författare)
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Health and quality of life in an aging population - Food and beyond
- 2016
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Ingår i: Food Quality and Preference. - : Elsevier BV. - 0950-3293 .- 1873-6343. ; 47, s. 166-170
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Tidskriftsartikel (refereegranskat)abstract
- In Europe the percentage of citizens aged 65 and over is increasing at an unprecedented rate, and is expected to account for over 30% of the population by 2050. Coupled with an increase in life expectancy, this massive demographic change calls for a major effort to ensure quality of life in our older population. A thorough understanding of the elderly as food consumers, their nutritional needs, their food perception and preferences is increasingly needed.The role of food in healthy aging was a prominent theme at the 6th European Conference on Sensory and Consumer Research, which had quality of life across the life span as a focal point. This short paper is based on a workshop held at the EuroSense meeting, focusing on research from sensory and consumer scientists. The workshop featured contributions focusing on food-related perception, needs and behavior of the elderly, and aimed at demonstrating the relevance of sensory and consumer scientists in promoting food-related well-being in an aging population. The workshop contributions are here reviewed and summarized three main themes: nutritional needs, food perception and aging, and behavioral drivers of food consumption.
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| 30. |
- Eberhardson, Michael, et al.
(författare)
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Randomised, Double-blind, Placebo-controlled Trial of CCR9-targeted Leukapheresis Treatment of Ulcerative Colitis Patients.
- 2017
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Ingår i: Journal of Crohn's & colitis. - : Oxford University Press (OUP). - 1876-4479 .- 1873-9946. ; 11:5, s. 534-542
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Tidskriftsartikel (refereegranskat)abstract
- Ulcerative colitis patients display increased numbers of circulating pro-inflammatory monocyte human leukocyte antigen-DR [HLA-DRhi] monocytes expressing high levels of the gut-homing C-C chemokine receptor 9 [CCR9] and tumour necrosis factor [TNF]-α. The aim of this first-in-human, double-blind, randomised, placebo-controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis, with regards to safety, tolerability, and immunological response.Patients with ulcerative colitis were treated every second day with leukapheresis during five sessions with a C-C chemokine ligand 25 [CCL25; CCR9 ligand] column or a placebo column.No major safety concerns were raised and the procedure was well tolerated. Pro-inflammatory HLA-DRhi cells decreased significantly in the active treatment group [p = 0.0391] whereas no statistically significant change was seen in the placebo group [p = 0.4688]. There was a significant decrease of HLA-DRhi monocytes in the active group compared with the placebo group when corrected for the imbalance in weight between the groups [p = 0.0105]. Mayo score decreased in the active group [p = 0.0156] whereas the change in the placebo group was not significant [p = 0.1250]. Mayo score ≤ 3 was observed in five out of 14 patients [35.7%] in the active group compared with one out of eight [12.5%] receiving placebo. The number of responders in the active treatment group was eight out of 14 patients [57.1%], whereas in the corresponding placebo group three out of eight patients [37.5%] responded to placebo. A dose-response correlation was observed between the blood volume processed and clinical outcome.This clinical induction trial using CCL25-tailored leukapheresis demonstrates a safe and effective removal of activated monocytes with a clinical effect in patients with ulcerative colitis.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Ekström, Jens-Ola, et al.
(författare)
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Replication of Ljungan virus in cell culture : the genomic 5'-end, infectious cDNA clones and host cell response to viral infections
- 2007
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Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 130:1-2, s. 129-139
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Tidskriftsartikel (refereegranskat)abstract
- Ljungan virus (LV) is a picornavirus recently isolated from bank voles (Clethrionomys glareolus). The previously uncharacterised 5'-end sequence of the LV genome was determined. Infectious cDNA clones were constructed of the wild type LV prototype strain 87-012 and of the cytolytically replicating cell culture adapted variant 87-012G. Virus generated from cDNA clones showed identical growth characteristics as uncloned virus stocks. Cell culture adapted LV, 87-012G, showed a clear cytopathic effect (CPE) at 3-4 days post-infection (p.i.). Virus titers, determined by plaque titration, increased however only within the first 18h p.i. Replication of LV (+) strand RNA was determined by real-time PCR and corresponded in time with increasing titers. In contrast, the amounts of the replication intermediate, the (-) strand, continued to increase until the cells showed CPE. This indicates separate controlling mechanisms for replication of LV (+) and (-) genome strands. Replication was also monitored by immunofluorescence (IF) staining. IF staining of both prototype 87-012 and the CPE causing 87-012G showed groups of 5-25 infected cells at 48h p.i., suggesting a, for picornaviruses, not previously described direct cell-to-cell transmission.
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| 37. |
- EL Hiar, Raida, et al.
(författare)
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Enteroviral Central Nervous System Infections in Children of the Region of Monastir, Tunisia : Diagnosis, Laboratory Findings of Cerebrospinal Fluid and Clinical Manifestations
- 2012
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Ingår i: Indian Journal of Virology. - : Springer Science and Business Media LLC. - 0970-2822 .- 0974-0120. ; 23:3, s. 294-302
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Tidskriftsartikel (refereegranskat)abstract
- Human enteroviruses (HEV) are one of the major causes of central nervous system (CNS) infections in pediatrics. A prospective study was conducted to assess the epidemiological, clinical, and laboratory characteristics of enterovirus (EV) infections of the CNS in children under 15-years-old, suspected of having viral CNS infections and admitted to the Pediatric Department of Monastir University Hospital, Tunisia. Enteroviral RNA was detected by 5' NCR nested RT-PCR assay in 33 % (20 out of 60) of cerebrospinal fluid specimens, whereas only six samples (10 %) were EV positive in cell culture. EV-positive patients were clustered according to their clinical manifestations, predominantly diagnosed as aseptic meningitis (65 %) and meningoencephalitis (20 %). Fever, headache, vomiting, and neck stiffness were the most pronounced symptoms. Pleocytosis with the predominance of lymphocytes was observed in 60 % of EV positive specimens. Although patients suffering from EV infections were encountered throughout the year, most occurred during spring and summer months. Using VP1-2A nested RT-PCR and sequence analysis, three of the 20 positive HEV were identified as Echovirus (E)-9. This is the first report of a cluster of aseptic meningitis cases caused by E-9 in Monastir.
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| 38. |
- Eriksson Ström, Jonas, et al.
(författare)
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Chronic obstructive pulmonary disease is associated with epigenome-wide differential methylation in BAL lung cells
- 2022
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - : American Thoracic Society. - 1044-1549 .- 1535-4989. ; 66:6, s. 638-647
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on BAL cells. Bronchoscopies were performed in 18 subjects with COPD and 15 control subjects (ex- and current smokers). DNA methylation was measured using the Illumina MethylationEPIC BeadChip Kit, covering more than 850,000 CpGs. Differentially methylated positions (DMPs) were examined for 1) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology, 2) accelerated aging using Horvath's epigenetic clock, 3) correlation with gene expression, and 4) colocalization with genetic variation. We found 1,155 Bonferroni-significant (P < 6.74 × 10-8) DMPs associated with COPD, many with large effect sizes. Functional analysis identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. Strong correlation was found between DNA methylation and chronological age but not between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL cells. Thirty-nine percent of DMPs were colocalized with COPD-associated SNPs. To the best of our knowledge, this is the first epigenome-wide association study of COPD on BAL cells, and our analyses revealed many differential methylation sites. Integration with mRNA data showed a strong functional readout for relevant genes, identifying sites where DNA methylation might directly affect expression. Almost half of DMPs were colocated with SNPs identified in previous genome-wide association studies of COPD, suggesting joint genetic and epigenetic pathways related to disease.
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| 39. |
- Ezzat, Kariem, et al.
(författare)
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PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation
- 2011
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 39:12, s. 5284-5298
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Tidskriftsartikel (refereegranskat)abstract
- Numerous human genetic diseases are caused by mutations that give rise to aberrant alternative splicing. Recently, several of these debilitating disorders have been shown to be amenable for splice-correcting oligonucleotides (SCOs) that modify splicing patterns and restore the phenotype in experimental models. However, translational approaches are required to transform SCOs into usable drug products. In this study, we present a new cell-penetrating peptide, PepFect14 (PF14), which efficiently delivers SCOs to different cell models including HeLa pLuc705 and mdx mouse myotubes; a cell culture model of Duchenne's muscular dystrophy (DMD). Non-covalent PF14-SCO nanocomplexes induce splice-correction at rates higher than the commercially available lipid-based vector Lipofectamine™ 2000 (LF2000) and remain active in the presence of serum. Furthermore, we demonstrate the feasibility of incorporating this delivery system into solid formulations that could be suitable for several therapeutic applications. Solid dispersion technique is utilized and the formed solid formulations are as active as the freshly prepared nanocomplexes in solution even when stored at an elevated temperatures for several weeks. In contrast, LF2000 drastically loses activity after being subjected to same procedure. This shows that using PF14 is a very promising translational approach for the delivery of SCOs in different pharmaceutical forms.
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| 40. |
- Feigenwinter, Christian, et al.
(författare)
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Spatial distribution of sensible and latent heat flux in the URBANFLUXES case study city Basel (Switzerland)
- 2017
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Ingår i: 2017 Joint Urban Remote Sensing Event (JURSE). Dubai; United Arab Emirates; 6-8 March 2017. - 9781509058099
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Konferensbidrag (refereegranskat)abstract
- Turbulent sensible and latent heat fluxes are calculated by a combined method using micrometeorological approaches (the Aerodynamic Resistance Method ARM), Earth Observation (EO) data and GIS-Techniques. The spatial distributions of turbulent heat fluxes were analyzed for 22 for the city of Basel (Switzerland), covering all seasons and different meteorological conditions. Seasonal variations in heat fluxes are strongly dependent on meteorological conditions, i.e. air temperature, water vapor saturation deficit and wind speed. The agreement of measured fluxes (by the Eddy Covariance method) with modeled fluxes in the weighted source area of the flux towers is moderate due to known drawbacks in the modelling approach and uncertainties inherent to EC measurements, particularly also in urban areas.
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| 41. |
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| 42. |
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| 43. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate methods in the development of a new tablet formulation : optimization and validation
- 2004
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Ingår i: Drug Development and Industrial Pharmacy. - New York : M. Dekker. - 0363-9045 .- 1520-5762. ; 30:10, s. 1037-1049
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study of the development of a tablet formulation approximately 100 excipients were characterized in screening experiments using multivariate design. Acceptable values for important responses were obtained with some of the formulations. The relationships between the properties of the excipients and the responses were evaluated using PLS. In this study additional experiments were performed in order to validate models obtained from the screening study and to find a formulation of suitable composition with desired tablet properties. A formulation with the desired disintegration time was found with the additional experiments and the agreement between observed and predicted values was fair for the tablets that did disintegrate. A limitation of this study was that tablets from four experiments did not disintegrate within the set time limit. The lack of agreement between observed and predicted values of these four experiments was probably due to the nature of one of the factors in the design. Considering the reduced experimental design the results are still encouraging.
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| 44. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate Methods in the Development of a New Tablet Formulation : Excipient Mixtures and Principal Properties
- 2006
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Ingår i: Drug Development and Industrial Pharmacy. - New York : M. Dekker. - 0363-9045 .- 1520-5762. ; 32:1, s. 7-20
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Tidskriftsartikel (refereegranskat)abstract
- A tablet formulation for direct compression has previously been studied using multivariate design. An optimization study of one of the most important tablet properties, disintegration time, revealed that excipients with Principal Properties (PP's) that were predicted as suitable by the model were not represented within the studied material.The feasibility of using mixtures of excipients in the multivariate approach to tablet formulation to solve this problem has been investigated in the present study. By mixing different excipients of the same excipient class, it should be possible to obtain mixtures with the predicted PP's, which in turn should give a formulation with the desired properties. In order to investigate the utility of this approach, separate mixture designs were applied to both binders and fillers (diluents).As reported here, the Partial Least Squares Projections to Latent Structures (PLS) model developed in the previously published screening study has been validated in the sense that the interesting region of the PP space identified in it has been shown to contain excipients, pure or mixed, that give the formulation suitable properties. Formulations with suitable properties were found with the mixture experiments. The local models also offer several alternatives for the composition of the formulation that yield the desired disintegration time.
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| 45. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate Methods in the Development of a New Tablet Formulation
- 2003
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Ingår i: Drug Development and Industrial Pharmacy. - New York : Marcel Dekker. - 0363-9045 .- 1520-5762. ; 29:10, s. 1053-1075
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Tidskriftsartikel (refereegranskat)abstract
- The overall objective of this article is to use an efficient approach to find a suitable tablet formulation for direct compression. By using traditional approaches to statistical experimental design in tablet formulation, the number of experiments quickly grows when many descriptive variables or many excipients are included. To facilitate the screening process, a multivariate design, which allows a systematical evaluation of a large number of excipients with a limited number of experiments, was implemented. Formulations with acceptable values for disintegration time and crushing strength were obtained with some of the formulations in the present study. The multivariate experimental design strategy yielded PLS models that will be used to identify a region of interest for the optimization. The strategy is general and can be applied in many different areas of pharmaceutical research and development.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Gessler, Michael, et al.
(författare)
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Didactics in VET - crisis, demands, concepts and open issues
- 2013
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Ingår i: Abstracts.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Four focus points (crisis, demands, concepts and open issues) are addressed from three different national perspectives (Sweden, Germany and Spain). Answers might be different, but challenges seem to be the same.(1) crisis: on the one hand we acknowledge a massive withdrawal of didactic discussion in the educational research: first the constructivism taught us that nobody can be taught (a nice antagonism), later the output orientation taught us that just the output counts and within the empirical turn of the educational sciences the topic didactics seems to be lost. (Chevallard, 2006, Moreno Herrera, 2012)(2) demands: On the other hand practitioners still expects that VET offers answers, methods and tools for their central questions: how can learners be empowered and learning be accelerated. Overall questions for the round table will therefore be: What implications have for didactics the fact that learning within this field happens in remarkably different context; namely, classroom and workshop? What is the value in developing a didactics for this specific complex learning context? Is the discourse on didactics a unique phenomenon for particular educational research traditions or is there a substance that is worth discussing? (Berglund & Lindberg, 2012; Ghaye, 2010)(3) concepts: One concept we want exemplary focus within this short proposal information: the didactic concept "task- and process-oriented learning". One concretization of this concept for the field of electrical trade is the so called "Competence toolbox“, which has been continuously developed for more than 10 years to give answers to the following practice-oriented research questions: How can work processes of skilled workers be analyzed and described? How can the results of work process analyses be transferred into work process oriented educational measures? What are the potentials of digital media and internet to support this work process orientation? How can these potentials be converted into task-oriented learning? (Howe & Knutzen, 2012).(4) open issues: see below "Conclusions, expected outcomes"Method:The overall approach of the above mentioned concept (as an example) is the so called Design-Based:Research: DBR characterized the methodical approach of converting the obtained results into work process oriented learning software. The learning software and the accordant task-oriented learning were tested in all learning venues, meaning companies, training centers and vocational schools. In detail following methods were used: (1) Expert workshops: In the first step expert workshops were held. These workshops were moderated by vocational scientists. Experienced master craftsman validated a list of spheres of activities through discussion. The agreed upon list of spheres of activities portrays the researched vocation. (2) Work process analysis: Related to every sphere of activity work process analysis had to be conducted in the second step. This approach is twofold from a methodological perspective. Initially the researcher led a qualitative interview with an experienced skilled worker or craftsman. (3) Online survey: The outcome of this kind of work process oriented learning was finally evaluated by an online survey of apprentices. After accomplishing a task the learners provided feedback relating to the learning software and task -oriented learning by filling in an online questionnaire.Expected outcomes:Expected outcomes of the round table is to fix (4) "open issues": In our view there is a great need to continue developing the basis of a didactic that will be encompassing and dynamic enough to deal with the complex and varied situation of guidance of the learning process in the VET field. In addition to the variety of context it is equally significant to consider the complexity derived from the various interacting components of the teaching and learning process. More is to be done in creating or continuing developing a didactics that encompasses the complexities of VET considering its different levels and different settings.
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| 50. |
- Giacalone, Davide, et al.
(författare)
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Health and quality of life in an aging population : food and beyond
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In Europe, as in much of the Western world, the number of citizens aged 65 and over has grown at an unprecedented rate and is expected to account for over 30% of the total population by 2060. Coupled with a steady increase in life expectancy, this massive demographic change calls for a major effort to ensure quality of life in our older population. A thorough understanding of the elderly as food consumers, their nutritional needs, and their food perception and preferences is increasingly recognized as key areas for future research.Food perception change at a later age as a result of the psychophysiological changes that occur with aging, such as decreased appetite and chemosensory acuity. The latter generally decrease food intake and the pleasure that the elderly derive from their meals, making the identification of possible compensation strategies (e.g., flavor enhancement, textural changes, etc.) essential to food producers interested in developing products for this increasingly important segment. Promoting food satisfaction among the elderly is also paramount to ensuring adequate nutritional intake. This aspect has major public health implications, such as preventing malnutrition and sarcopenia, which are leading causes of decreased independence and lower quality of life. Additionally, the importance of social and psychological factors is increasingly recognized. Many conditions related to aging (e.g., tiredness, loneliness) may prevent elderly people from preparing and enjoying meals, calling for alternative vehicles – such as tailor-made distribution channels, social food preparation and eating situations – for promoting healthy eating.In this workshop, a range of international speakers with relevant professional experience will present their latest work. More generally, it is our intention with this workshop to raise awareness of how sensory and consumer research can contribute to promote well-being among the elderly, and ultimately to expand the number of healthy life years as we age.
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