1. |
|
|
2. |
- Wegrzyniak, Olivia, et al.
(author)
-
Imaging of fibrogenesis in the liver by [18F]TZ-Z0959 : an Affibody molecule targeting platelet derived growth factor receptor β
- 2023
-
In: EJNMMI Radiopharmacy and Chemistry. - : Springer Nature. - 2365-421X. ; 8:1
-
Journal article (peer-reviewed)abstract
- Background: Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFRβ could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to evaluate a fluorine-18 radiolabeled Affibody molecule ([18F]TZ-Z09591) as a PET tracer for imaging liver fibrogenesis. Results: In vitro specificity studies demonstrated that the trans-Cyclooctenes (TCO) conjugated Z09591 Affibody molecule had a picomolar affinity for human PDGFRβ. Biodistribution performed on healthy rats showed rapid clearance of [18F]TZ-Z09591 through the kidneys and low liver background uptake. Autoradiography (ARG) studies on fibrotic livers from mice or humans correlated with histopathology results. Ex vivo biodistribution and ARG revealed that [18F]TZ-Z09591 binding in the liver was increased in fibrotic livers (p = 0.02) and corresponded to binding in fibrotic scars. Conclusions: Our study highlights [18F]TZ-Z09591 as a specific tracer for fibrogenic cells in the fibrotic liver, thus offering the potential to assess fibrogenesis clearly. Graphical abstract: [Figure not available: see fulltext.]
|
|
3. |
- Bergemalm, Daniel, 1977-, et al.
(author)
-
Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
-
In: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
-
Journal article (peer-reviewed)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.
|
|
4. |
- Bergquist, Filip, et al.
(author)
-
Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
- 2022
-
In: Neurology. - : Lippincott, Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 99:10, s. E965-E976
-
Journal article (peer-reviewed)abstract
- Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
|
|
5. |
- Bergs, Per, et al.
(author)
-
Values of urban greening : Voices of residents on highly intensive densification (HID) in a Swedish case study
- 2024
-
In: Urban Forestry & Urban Greening. - : Elsevier. - 1618-8667 .- 1610-8167. ; 99
-
Journal article (peer-reviewed)abstract
- Effects of planned Highly Intensive Densification (HID) were investigated in southern Eriksberg, a residential area located four km from the city center, mainly built in the 1950s in western Uppsala, Sweden according to the planning ideal Houses-in-Park. Uppsala municipality has proposed a doubling of the number of apartments in the southern part of the residential area, mostly through situating dwellings in-between existing houses and in some of the existing green places and spaces. This way of densifying by inserting an equally large area is a new approach in larger Swedish cities, which we term HID. The research presented in this paper is based on case study methodology. Method triangulation has been used to elucidate the projected consequences on urban greening of the planned HID-process in southern Eriksberg. We have analysed the development plan of Eriksberg and measurable effects but also inventoried attitudes and experiences among residents. The document study showed that an implementation of the HID plan will transform the original concept Houses-in-Park into a compact design with significant smaller green spaces in between the houses. The main result showed that most of the respondents had in general strong opinions and feelings regarding the planned loss of green structure. The courtyard green, the district green and the entrance green were highly valued by the respondents. Further on it was clear that a majority were concerned about the residential area losing its original character, planned according to the idea, Houses-in-Park.
|
|
6. |
- Björck, Niclas, et al.
(author)
-
Keramik : I: UV GAL Rapport 200:14. Snåret.Aspekter på sten-, brons och järnålder i Vendel, Väg E4, sträckan Uppsala-Mehedeby, Uppland, Vendels socken, Fallsboda 1:2, Karby 29:5, RAÄ 291
- 2007
-
Reports (pop. science, debate, etc.)abstract
- Arkeologisk undersökning av boplats med lämningar från neolitikum, yngre bronsålder och vendeltid. På platsen fanns även sannolika gravar. Analyser görs av hus, keramik, pollen mm. Platsen har under vendeltid utnyttjats för tjärframställning
|
|
7. |
- Eriksson, Annika K., et al.
(author)
-
Influence of iron addition on the oxygen-deficient Sr0.85Bi0.15Co1-xFexO3-delta (0.0 <= x <= 1.0) perovskites
- 2008
-
In: Journal of Solid State Chemistry. - : Elsevier BV. - 0022-4596 .- 1095-726X. ; 181:8, s. 2031-2040
-
Journal article (peer-reviewed)abstract
- A series of oxygen-deficient Sr0.85Bi0.15Co1-xFexO3-delta (0.0 <= x <= 1.0) perovskite phases were prepared using solid-state reaction. Results of neutron powder diffraction analyses show that the introduction of Fe onto the B-site severely effects the long range coherence of the oxygen vacancy ordered, 14/mmm supercell, observed for the x = 0.0 sample. For x = 0.1 a smaller, a = b approximate to a(p), c approximate to 2a(p), P4/mmm supercell gives the best agreement to the diffraction data, whilst phases in the range 0.2 <= x <= 0.6 adopt disordered cubic perovskite structures. Pseudo-cubic, a = b approximate to a(p), c approximate to a(p), structures are found for x >= 0.8. Evidence of weak superstructures, reflecting local oxygen ordering, is also obtained from electron diffraction. For all oxygen-annealed phases the average structure reverts to cubic Pm (3) over barm. The as-prepared samples show G-type antiferromagnetic order at room temperature. The oxygen annealed x = 0.10, 0.25 and 1.0 samples display low-temperature spin-glass transitions.
|
|
8. |
- Eriksson, Anna U., et al.
(author)
-
Near infrared optical projection tomography for assessments of beta-cell mass distribution in diabetes research
- 2013
-
In: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; 71
-
Journal article (peer-reviewed)abstract
- By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen's (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR)2; 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction2 and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations3. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans.
|
|
9. |
- Eriksson, Fredrik, et al.
(author)
-
Golf courses as a part of Urban Green Infrastructure: Social aspects of Golf Courses and Extensively Managed Turfgrass areas from Nordic Perspective.
- 2015
-
Conference paper (peer-reviewed)abstract
- Originated in Scotland in the 15th century the game of golf started to be very popular first in Europe and later in all English colonies and finally, by the end of the 20th century, around the world. In the Nordic countries turf grasses and golf facilities are increasing since the second part of the 20th century. The Nordic golf federations have 900 000 members, playing golf on more than 900 courses that cover a total area of more than 58 000 ha. The popularity of golf is directly connected to the growing of market economy. In the end of the 20th –beginning of the 21 century, in the era of globalisation, golf started to be one of the very important symbols of business success and a very popular pastime game. We research golf courses within the interdisciplinary project “Lawn as the cultural and ecological phenomenon” run by scientists from SLU, Sweden and funded by the Swedish Research Council. One of the goals of this project was to study the gradient of different managed lawns from the most intensively managed to the more meadow like lawns. Golf courses in this sense can be seen as a microcosm itself where all types of planted grass communities (lawns) are presented (fairway, rough and high rough). Six golf courses, two courses nearby three cities (Uppsala, Malmö and Gothenburg) have been investigated. In these courses six holes have been sampled for both environmental and ecological parameters. After contacts and discussions with managers responsible for six golf courses in three regions a total number of 180 interviews been conducted. This research was supported by STERF (Scandinavian Turfgrass and Environmental Research Foundation). Last decade in Sweden there is a growing movement of creating multifunctional golf courses which can provide a whole range of ecosystem services such as improving biodiversity and providing recreational areas which are accessible for the public. STERF is one of the main promoters of this movement. The social part of this study has been focused on golf courses and their significance from the golf players' perspective. The main research question was “What is valued by golfers in their golf course environment when it comes to the green environment and ecological, cultural and social values”. The interviews indicate that the golf course and time spent on the golf course include so much more than the sport itself. For many players the visits at the golf course also act as experience of nature and beautiful surroundings as well as in a social context, a way to stay in shape (fitness) as well as a way to relax (recreation). Natural values that are often mentioned by the interviewees is quiet, peaceful environment (silence), the chirping of birds, butterflies and other small animals as well as shrubs, trees and plantings. Although the existence of "natural environment" is perceived as a positive example, said one of the golfers: "it is so beautiful with birch trees and meadow flowers available as background for this golf course". Golf players also enjoy things like silence, nice smells and sounds from the nature as well as presence of water (lake, pond and river). Golf courses have great potential to support multiple values, for biodiversity and carbon sequestration and social wellbeing of people. Further work in this project will include analysis of trade-offs and synergies between the different research fields.
|
|
10. |
- Eriksson, Gunilla, et al.
(author)
-
Diet and mobility among Mesolithic hunter-gatherers in Motala (Sweden) - The isotope perspective
- 2018
-
In: Journal of Archaeological Science. - : Elsevier BV. - 2352-409X .- 2352-4103. ; 17, s. 904-918
-
Journal article (peer-reviewed)abstract
- Recent excavations at the sites of Strandvägen and Kanaljorden in Motala, Eastern Central Sweden, have unearthed complex and varied funerary remains from the Mesolithic. The two sites are situated on opposite banks of the river Motala Ström. While geographically close and roughly covering the same time span (c. 8000–7000 cal. BP), the funerary remains reveal differences and similarities in the treatment of the dead between the two localities. While at Strandvägen human bones were mostly found either scattered along the river bed or in inhumation graves, Kanaljorden contains wetland depositions of disarticulated skulls. We have conducted multi-isotope analyses of δ13C, δ15N, δ34S and 87Sr/86Sr of human and animal remains with the aim of reconstructing the dietary patterns, geographic provenance and mobility of the interred. A series of faunal reference samples and, in the case of 87Sr/86Sr, soil samples have been analysed in order to establish relevant isotopic baselines. The results show a protein intake dominated by aquatic resources, probably consisting of both freshwater and marine fish in varied proportions. The strontium isotope data indicate an interesting distinction between the individuals buried on either side of the river Motala Ström. Five out of six sampled individuals from Strandvägen have isotope ratios consistent with a local provenance, whereas ratios from seven out of eight Kanaljorden individuals indicate a non-local origin. The δ34S analysis proved problematic as a majority of the samples appear to be affected by diagenesis. This is probably the result of contamination by exogenous sulphur from surrounding fluvial and lacustrine sediments, as has previously been reported from other waterlogged sites.
|
|
11. |
- Eriksson Lundström, Jenny, et al.
(author)
-
Featuring Sustainability - social sustainability impact of Open Innovation Software
- 2012
-
In: The proceedings of the 5th ISPIM Innovation Symposium.
-
Conference paper (peer-reviewed)abstract
- As ICT has shown itself useful when it comes to promoting sustainability performance internally as well as externally to the organization, it also relates to the concept of sustainable development. Unfortunately, research on features of Open Innovation Software and their sustainability impact, as well as more general research on Open Innovation and organizational sustainability performance are scarce. By means of the core areas of sustainability Bengtsson et al 2012 we research sustainability relatedness of common features of idea management systems. The research shows that the investigated features are mainly directed towards providing user engagement, while features related to transparency, incentives and efficiency all may be seen as indirect effects of providing for user engagement in the idea management system. As a consequence, issues related to transparency, incentives and efficiency that may ensure innovativeness of the ideas and positive social sustainability as an outcome of the user experience, are placed on the manager.
|
|
12. |
|
|
13. |
- Eriksson, Per Erik
(author)
-
Videography as Design Nexus : Critical Inquires into the Affordances and Efficacies of Live-action Video Instructions
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- This thesis is about live-action instructional videos (LAVs). By addressing design problems with respect to the how-to video genre, the thesis asks fundamental questions about mediated instructional communication efficacies and the factors that either obstruct or augment them. The analysis presented in this thesis is based on the notion that videography is a design nexus and key focal point of the connections that make live-action video instructional efforts possible. This Design Nexus is explored by defining and illuminating key ontological dimensions, medium specificities and the video users’ cognitive capacities. This is to acknowledge that the users of instructions in this thesis are center stage, both as biological and cultural beings.The methods used in this thesis and its associated papers are eye-tracking, video observations, questionnaires, self-reports, focus group interviews and YouTube analytics. Hence, both numerical data and non-numerical data are analyzed in this study.The results of the analyses indicate that pre-production planning is key in live-action video instructional endeavors, but not at the expense of the videographer’s status as designer. Moreover, the analyses show that users’ cognitive processing and visual decoding depend on the power of the live-action format to show actual human behavior and action. Other presented evidence seems to infer that LAV-instructions are a little less demanding if users apply a focused decoding style when interacting with them. Nevertheless, physiological engagement of this kind is likely not to fully compensate for users’ psychological engagement.This thesis contributes to a more comprehensive understanding of humans’ abilities to interpret the actions of others via medial means. By relating this to video medium-specific affordances, this thesis also furthers important efficacy distinctions and boundary conditions. This understanding is considered important for live-action video makers and designers of visual instructions as well as scholars who need to develop better methods to assess users’ behavioral engagement when they interact with digital instructional media.
|
|
14. |
- Eriksson, Pontus, et al.
(author)
-
Urodrill - a novel MRI-guided endoscopic biopsy technique to sample and molecularly classify muscle-invasive bladder cancer without fractionating the specimen during transurethral resection
- 2023
-
In: European Urology Open Science. - 2666-1691. ; 53, s. 78-82
-
Journal article (peer-reviewed)abstract
- The current diagnostic pathway for patients with muscle-invasive bladder cancer (MIBC), which involves with computed tomography urography, cystoscopy, and transurethral resection of the bladder (TURB) to histologically confirm MIBC, delays definitive treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) has been suggested for MIBC identification using magnetic resonance imaging (MRI), but a recent randomized trial reported misclassification in one-third of patients. We investigated a new endoscopic biopsy device (Urodrill) for histological confirmation of MIBC and assessment of molecular subtype by gene expression in patients with VI-RADS 4 and 5 lesions on MRI. In ten patients, Urodrill biopsies were guided by MR images to the muscle-invasive portion of the tumor via a flexible cystoscope under general anesthesia. During the same session, conventional TURB was subsequently performed. A Urodrill sample was successfully obtained in nine of ten patients. MIBC was verified in six of nine patients, and seven of nine samples contained detrusor muscle. In seven of eight patients for whom a Urodrill biopsy sample was subjected to RNA sequencing, single-sample molecular classification according to the Lund taxonomy was feasible. No complications related to the biopsy device occurred. A randomized trial comparing this new diagnostic pathway for patients with VI-RADS 4 and 5 lesions and the current standard (TURB) is warranted. Patient summary: We report on a novel biopsy device for patients with muscle-invasive bladder cancer that facilitates histology analysis and molecular characterization of tumor samples.
|
|
15. |
|
|
16. |
- Fokkema, Marieke L., et al.
(author)
-
Outcome after percutaneous coronary intervention for different indications : long-term results from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
- 2016
-
In: EuroIntervention. - Toulouse, France : Europa Edition. - 1774-024X .- 1969-6213. ; 12:3, s. 303-311
-
Journal article (peer-reviewed)abstract
- Aims: The aim of this study was to evaluate clinical outcome for different indications for PCI in an unselected, nationwide PCI population at short- and long-term follow-up.Methods and results: We evaluated clinical outcome up to six years after PCI in all patients undergoing a PCI procedure for different indications in Sweden between 2006 and 2010. A total of 70,479 patients were treated for stable coronary artery disease (CAD) (21.0%), unstable angina (11.0%), non-ST-elevation myocardial infarction (NSTEMI) (36.6%) and ST-elevation myocardial infarction (STEMI) (31.4%). Mortality was higher in STEMI patients at one year after PCI (9.6%) compared to NSTEMI (4.7%), unstable angina (2.2%) and stable CAD (2.0%). At one year after PCI until the end of follow-up, the adjusted mortality risk (one to six years after PCI) and the risk of myocardial infarction were comparable between NSTEMI and STEMI patients and lower in patients with unstable angina and stable CAD. The adjusted risk of stent thrombosis and heart failure was highest in STEMI patients.Conclusions: The risk of short-term mortality, heart failure and stent thrombosis is highest for STEMI patients after PCI. Therapies to reduce stent thrombosis and heart failure appear to be most important in decreasing mortality in patients with STEMI or NSTEMI undergoing PCI.
|
|
17. |
- Hersi, Abdi-Fatah, et al.
(author)
-
Optimizing Dose and Timing in Magnetic Tracer Techniques for Sentinel Lymph Node Detection in Early Breast Cancers: The Prospective Multicenter SentiDose Trial
- 2021
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 13:4
-
Journal article (peer-reviewed)abstract
- Simple Summary Superparamagnetic iron oxide (SPIO) nanoparticles have comparable performance to the combination of radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) biopsy in breast cancer. In this multicenter prospective study, lower SPIO doses (undiluted 1.5 vs. 1.0 mL) in different timeframes (perioperative vs. 1-7 days preoperative) and injection sites (subareolar vs. peritumoral) were compared to the previous standard (diluted 2.0 mL perioperatively) from the earlier Nordic trial. RI + BD were co-administered as background. In total, 534 patients were analyzed. SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and respectively non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 mL and the Nordic cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Thus, SPIO at 1.5 and 1.0 mL was non-inferior to both Sienna+(R) and the dual technique for SLN detection. Superparamagnetic iron oxide nanoparticles (SPIO) are non-inferior to radioisotope and blue dye (RI + BD) for sentinel lymph node (SLN) detection. Previously, 2 mL SPIO (Sienna+(R)) in 3 mL NaCl was used. In this dose-optimizing study, lower doses of a new refined SPIO solution (Magtrace(R)) (1.5 vs. 1.0 mL) were tested in different timeframes (0-24 h perioperative vs. 1-7 days preoperative) and injections sites (subareolar vs. peritumoral). Two consecutive breast cancer cohorts (n = 328) scheduled for SLN-biopsy were included from 2017 to 2019. All patients received isotope +/- blue dye as back-up. SLNs were identified primarily with the SentiMag(R) probe and thereafter a gamma-probe. The primary endpoint was SLN detection rate with SPIO. Analyses were performed as a one-step individual patient-level meta-analysis using patient-level data from the previously published Nordic Trial (n = 206) as a third, reference cohort. In 534 patients, the SPIO SLN detection rates were similar (97.5% vs. 100% vs. 97.6%, p = 0.11) and non-inferior to the dual technique. Significantly more SLNs were retrieved in the preoperative 1.0 mL cohort compared with 1.5 and the 2.0 mL cohorts (2.18 vs. 1.85 vs. 1.83, p = 0.003). Lower SPIO volumes injected up to 7 days before the operation have comparable efficacy to standard SPIO dose and RI + BD for SLN detection.
|
|
18. |
- Hieronymus, Fredrik, 1986, et al.
(author)
-
Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression.
- 2016
-
In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 21:4, s. 523-30
-
Journal article (peer-reviewed)abstract
- The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (P<0.001). The observation that 29 out of 32 comparisons detected an antidepressant signal from the tested SSRI suggests the effect of these drugs to be more consistent across trials than previously assumed. Further, the frequent use of the HDRS-17-sum as an effect parameter may have distorted the current view on the usefulness of SSRIs and hampered the development of novel antidepressants.Molecular Psychiatry advance online publication, 28 April 2015; doi:10.1038/mp.2015.53.
|
|
19. |
- Hieronymus, Fredrik, 1986, et al.
(author)
-
The alleged ineffectiveness of SSRIs in depression is an artefact caused by the use of an inappropriate measure of efficacy
- 2014
-
In: International Journal of Neuropsychopharmacology vol. 17 Supplement 1. 29th CINP World Congress of Neuropsychopharmacology, Vancouver, Canada, 22–26 June 2014. - New York : Cambridge University Press. - 1461-1457 .- 1469-5111.
-
Conference paper (other academic/artistic)abstract
- Objective: Many studies have questioned if summation of the scores of the 17 disparate items constituting the Hamilton Depression Rating Scale (HDRS-17) is a reliable index of severity in depression; yet the cur- rent questioning of the ef fi cacy of antidepressant drugs is to a large extent based on the assumption that response to treatment is reliably re fl ected by this instrument. We aimed to investigate the possibility that the shortcom- ings of the HDRS may contribute to the failure of antidepressants to out- perform placebo in many trials. Methods: We analyzed thirteen industry-sponsored trials of selective serotonin reuptake inhibitors (SSRIs) comprising twenty-four drug- placebo comparisons and including patient-level data from 5381 subjects (administered paroxetine, citalopram, fl uoxetine, or placebo), the aim being to assess what the outcome would have been if the single item de- pressed mood (rated 0 – 4) had been used as measure of ef fi cacy. Results: While 12 out of 24 comparisons (50%) revealed a signi fi cant difference between active drug and placebo at week 6 with respect to re- duction in HDRS-17-sum, 23 out of 24 comparisons (96%) showed the ac- tive drug to be superior to placebo in reducing depressed mood. Correspondingly, a pooled analysis of all cases showed the effect size when assessed using the HDRS-17-sum to be 0.30, whereas it, when mea- sured using the depressed mood item alone, was 0.42. Conclusion: While not claiming that measuring one item only is the most appropriate way of recording symptom severity in depression, we do suggest that the inclusion of a number of varying symptoms in the as- sessment, some of which may be side-effects of treatment and/or are unre- lated to the disorder, reduces the sensitivity to detect a difference between active drug and placebo. This lack of sensitivity of HDRS-17 might partly explain why a high fraction of antidepressant trials fail to reveal a signi fi - cant difference between treatment groups
|
|
20. |
- Holmin, Susanne, et al.
(author)
-
Investigation of Electrode Materials as Sensors in a Voltammetric Electronic Tongue
- 2002
-
In: Electroanalysis. - Weinheim, Germany : Wiley-VCH Verlagsgesellschaft. - 1040-0397 .- 1521-4109. ; 14:12, s. 839-847
-
Journal article (peer-reviewed)abstract
- In this work different electrode materials were investigated as sensors in a voltammetric electronic tongue. Basically, the electronic tongue is based on the combination of nonspecific sensors (electrodes) and pattern recognition tools, for example principal component analysis (PCA). Copper. glassy carbon, nickel, palladium, silver, tin, titanium and zirconium together with more traditional electrode materials such as gold, iridium, and platinum were studied. Cyclic voitammetry was applied to study typical model reactions in solutions containing different electroactive compounds, like ascorbic acid, glucose, histidine and potassium hexacyanoferrate(II). Different sensitivity and selectivity were obtained with the electrodes. Large responses were for example found for the amino acid and the carbohydrate using the copper, nickel and silver electrode. Some of the electrodes were employed in multicomponent solutions, i.e., liquid washing detergents from different suppliers together with differential pulse voltammetry. Responses from the electrodes in combination with PCA showed that they separated the detergents to different extents. This was further used when information from the sensors was merged together for successful discrimination of the detergents. It was found that two detergents close to each other in the score plot were from the same supplier. Furthermore. scanning electron microscopy (SEM) was used to monitor surface changes at the nonnoble electrodes (copper, nickel, and silver).
|
|
21. |
- Ignatieva, Maria, et al.
(author)
-
Pros and cons of transdisciplinary research: A case study of Swedish lawns and their sustainable alternatives
- 2020
-
In: Urban Forestry & Urban Greening. - : Elsevier BV. - 1618-8667 .- 1610-8167. ; 56
-
Journal article (peer-reviewed)abstract
- In this article, we discuss the pros and cons of transdisciplinary research using the results of a research project on lawns carried out in Sweden from 2013 to 2016. We viewed lawns as a complex ecological and cultural phenomenon and searched for different sustainable lawn solutions in urban areas of Sweden.Constraints on the research included the time and effort required for team members to become familiar with the different research approaches, participate in regular meetings and agree on joint methodology. Later in the project, the integration, analysis and understanding of field data, theoretical sources and practical implementation approaches were also time-consuming obstacles. Thus, the initial and final phases of the project were extremely important and demanded a lot of time and effort. Especially challenging was the cross-use of different methodologies from natural and social sciences. Such ambitious multiscale and multitask projects dealing with living urban nature and people require at least five years to complete, rather than the three years typically suggested for classical research projects.The pros of the transdisciplinary approach was its ability to incorporate results of natural and social studies into landscape design, the ability to involve stakeholders in different project activities and to disseminate the research results in practice. This research revealed that lawns are a relatively recent phenomenon that is still expanding globally. The social study component showed that mowing and creating smooth, green lawn surfaces is important to stakeholders (lawn users, planners and managers). However, in Sweden, there is a tendency for local citizens to accept more biodiverse plant communities. Working closely with open-minded stakeholders led to the real implementation of lawn alternatives, which, in turn, increased media attention. The initial concept—that management was a central factor to the whole transdisciplinary project—was confirmed. The goal of this article is to share the unique experiences and lessons learned by researchers of conducting transdisciplinary research and to make such complex research more successful.
|
|
22. |
- Ignatieva, Maria, et al.
(author)
-
The lawn as a social and cultural phenomenon in Sweden
- 2017
-
In: Urban Forestry & Urban Greening. - : Elsevier BV. - 1618-8667 .- 1610-8167. ; 21, s. 213-223
-
Journal article (peer-reviewed)abstract
- Lawns have a significant influence on the cityscape as one of the essential elements of green spaces and an important part of people's everyday lives. Most people in the Western world view lawns as a compulsory element of the urban landscape, almost an icon, without questioning their social, symbolic, ecological or aesthetic values. This research is a part of the conceptual framework and methodological approaches that are being used in an ongoing transdisciplinary collaboration project to study lawns in Sweden as a social and ecological phenomenon.The overall aim of this study was to investigate social and cultural perceptions of lawns, as well as motives behind decisions about the establishment and management of lawns in Sweden. Two multifamily housing typologies, the 'Million Programme' and People's Homes', were examined due to their dominance in Swedish cities. We also studied how an alternative vision of conventional lawns can be applied and accepted by urban residents. We estimated lawn cover in multi-family housing areas and links to people's perception and use of lawns. Questionnaires, semi-structured interviews and observational studies were used (N = 300). Our results showed that people like lawns even if they do not always directly use them. Lawns cover the most significant amount of outdoor spaces in all multi-family residential areas and accompany people everywhere from the house to the schoolyard or park. The total lawn cover in the study areas was 27.8%. Lawns were particularly valued as important places for different outdoor activities (playing, resting, picnicking, walking, socialising) and enjoying the green colour. However people do not want to use a vast monotonous lawn, but a variety of spaces that provide good conditions for different senses ( sound, smell, touch and sight) and activities. Alternative lawns were also appreciated by many citizens, politicians, planners and managers. The implementation of new types of lawns requires special planning and design solutions adjusted for each particular neighbourhood. (C) 2016 The Authors. Published by Elsevier GmbH.
|
|
23. |
|
|
24. |
- Karlsson, Oskar, et al.
(author)
-
Pesticide-induced multigenerational effects on amphibian reproduction and metabolism
- 2021
-
In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 775
-
Journal article (peer-reviewed)abstract
- Underlying drivers of species extinctions need to be better understood for effective conservation of biodiversity. Nearly half of all amphibian species are at risk of extinction, and pollution may be a significant threat as seasonal high-level agrochemical use overlaps with critical windows of larval development. The potential of environmental chemicals to reduce the fitness of future generations may have profound ecological and evolutionary implications. This study characterized effects of male developmental exposure to environmentally relevant concentrations of the anti-androgenic pesticide linuron over two generations of offspring in Xenopus tropicalis frogs. The adult male offspring of pesticide-exposed fathers (F1) showed reduced body size, decreased fertility, and signs of endocrine system disruption. Impacts were further propagated to the grand-offspring (F2), providing evidence of transgenerational effects in amphibians. The adult F2 males demonstrated increased weight and fat body palmitoleic-to-palmitic acid ratio, and decreased plasma glucose levels. The study provides important cross-species evidence of paternal epigenetic inheritance and pollutant-induced transgenerational toxicity, supporting a causal and complex role of environmental contamination in the ongoing species extinctions, particularly of amphibians.
|
|
25. |
- Leffler, Tomas, 1962, et al.
(author)
-
Monitoring of bed material in a biomass fluidized bed boiler using an electronic tongue
- 2023
-
In: Fuel. - : Elsevier BV. - 0016-2361 .- 1873-7153. ; 340
-
Journal article (peer-reviewed)abstract
- The thermal conversion of biomass fuel mixes in fluidized beds can cause agglomeration. To counteract agglomeration, bed material is gradually exchanged with virgin bed material, and this results in increased disposal of used bed material. Furthermore, the bed material exchange represents a costly option, as it involves a cost for virgin bed material, for landfill, and for unplanned downtime of the plant. This paper presents a novel method for the evaluation of bed material quality: the electronic tongue (ET). Evaluation of bed material quality can contribute toward decreasing the cost of unnecessary exchanges of bed material. The proposed method was tested on bed material sampled on an almost daily basis from a commercial fluidized bed boiler during several months of operation. A two-electrode ET was used for the evaluation of the bed material quality. The analysis relied on pulsed voltammetry measurements and multivariate data analysis with Principal Component Analysis (PCA). The results suggest that it is possible to follow bed material changes and that the ET, after further development, may be used to optimize the material flows connected to the bed material. Further research is being conducted to optimize the ET's performance and its application in monitoring bed material.
|
|
26. |
- Lind, Lars, et al.
(author)
-
Obesity is associated with coronary artery stenosis independently of metabolic risk factors : the population-based SCAPIS study
- 2022
-
In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 362, s. 1-10
-
Journal article (peer-reviewed)abstract
- Background and aims: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. Methods: In the SCAPIS study (50–65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. Results: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34–1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87–1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. Conclusions: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.
|
|
27. |
- Locke, Adam E, et al.
(author)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
|
|
28. |
-
Militärhistorisk tidskrift 2011-2012
- 2013
-
Editorial collection (other academic/artistic)abstract
- Förord - Fredrik ErikssonDet militärhistoriska 2012 - Per IkoMilitärhistoriens roll i USA - intryck från en vistelse vid Ohio State University - Gunnar ÅseliusArtiklar och uppsatserMagnus Stenbock - myten, bilderna och mannen - Björn AskerKrigets historiografiska funktion - framställningar av krig i svensk historieskrivning 1747-1857 - Hampus Östh GustafssonHistoria som värdegemenskap - finsk, estnisk och svensk historia i polska ögon under mellankrigstiden - Piotr WawrzeniukRapport från det militära samarbetets vardag - finska militärattacheers syn på Sverige och svensk-finsk militär samverkan, 1924-1939 - Anders AhlbäckMed staten som husvärd - en undersökning av officerarnas inkvartering inom indelningsverket 1776-1807 - Christopher ArunasalamLokalsamhället som resurs och som objekt för skador under Napoleonkrigen - följderna av den ryska armens logistiska lösningar i Vasa län under finska kriget 1808-1809 - ]ussi JääskeläinenDisciplinering av indelta och värvade kavallerister under 1800- och 1900-talen - ett civilisationsfenomen? - Börje EkenvallRecensionerMyten om äran och eliten - erfarenheter från andra världskriget - anmälan av Dan ÖbergNorska specialförband - från Milorg till Afghanistan - anmälan av Lars Ericsson WolkeMoral och småstatsperspektiv - anmälan av Henrik EdgrenAndra världskriget än en gång - anmälan av Lars Ericsson WolkeBland gravstenar, skelett och minnen - anmälan av Lars Ericsson WolkeHistorien och de stora männen - anmälan av Fredrik ErikssonKalla kriget lokalt - anmälan av Sten Munck af RosenschöldKustförsvar i norr - anmälan av Sten Munck af RosenschöldTotalförsvaret i Skåne beskrivet i detalj - anmälan av Sten Munck af RosenschöldVardagsspråkets krigiska natur? - anmälan av Thomas RothTvå journalister i Afghanistan - anmälan av Mikael Wendt"Den här gången kommer allt att bli annorlunda" - Afghanistan 1979-89 - anmälan av Fredrik ThisnerGrannar på gränsen till sammanbrott - slaget vid Adrianopel år 378 - anmälan av Fredrik ThisnerFrån mellanblå via fältgrå till kamouflage modell 90 - anmälan av Dag EckerbergSvensk general i amerikanska inbördeskriget - anmälan av Jimmy EngrenTankeväckande om diktaturernas minsta byggstenar - anmälan av Lars Ericsson WolkeEn fruktansvärd och läsvärd skildring - anmälan av Fredrik ErikssonOm kvinnornas inträde i militär verksamhet - anmälan av Esbjörn LarssonPå spaning efter ett kustartilleri som försvunnit - anmälan av Sten Munck af RosenschöldSamband, samband, samband! - anmälan av Sten Munck af RosenschöldBeordrad ellerfrivillig? - anmälan av Thomas RothNordamerikanska indianers krig - anmälan av Lars Rössle
|
|
29. |
|
|
30. |
- Näslund, Jakob, et al.
(author)
-
Incidence of early anxiety aggravation in trials of selective serotonin reuptake inhibitors in depression
- 2017
-
In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 136:4, s. 343-351
-
Journal article (peer-reviewed)abstract
- © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: Selective serotonin reuptake inhibitors (SSRIs) may aggravate anxiety and agitation during the first days of treatment but the frequency of such reactions remains unknown. Method: We analysed patient-level data from placebo-controlled trials of sertraline, paroxetine or citalopram in depressed adults. Somatic anxiety, psychic anxiety and psychomotor agitation as assessed using the Hamilton Depression Rating Scale (HDRS) were analysed in all trials (n=8262); anxiety-related adverse events were analysed in trials investigating paroxetine and citalopram (n=5712). Results: After one but not two weeks, patients on an SSRI were more likely than those on placebo to report enhanced somatic anxiety (adjusted risk 9.3% vs. 6.7%); likewise, mean rating of somatic anxiety was higher in the SSRI group. In contrast, patients receiving an SSRI were less likely to report aggravation of psychic anxiety (adjusted risk: 7.0% vs. 8.5%) with mean rating of psychic anxiety and agitation being lower in the SSRI group. The adverse event ‘nervousness’ was more common in patients given an SSRI (5.5% vs. 2.5%). Neither aggravation of HDRS-rated anxiety nor anxiety-related adverse events predicted poor antidepressant response. Conclusion: Whereas an anxiety-reducing effect of SSRIs is notable already during the first week of treatment, these drugs may also elicit an early increase in anxiety in susceptible subjects that however does not predict a poor subsequent response to treatment.
|
|
31. |
|
|
32. |
|
|
33. |
- Shungin, Dmitry, et al.
(author)
-
New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
-
Journal article (peer-reviewed)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
|
|
34. |
- Speliotes, Elizabeth K., et al.
(author)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Journal article (peer-reviewed)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
35. |
- Spreco, Armin, et al.
(author)
-
Nowcasting (Short-Term Forecasting) of COVID-19 Hospitalizations Using Syndromic Healthcare Data, Sweden, 2020
- 2022
-
In: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 28:3, s. 564-571
-
Journal article (peer-reviewed)abstract
- We report on local nowcasting (short-term forecasting) of coronavirus disease (COVID-19) hospitalizations based on syndromic (symptom) data recorded in regular healthcare routines in Östergötland County (population ≈465,000), Sweden, early in the pandemic, when broad laboratory testing was unavailable. Daily nowcasts were supplied to the local healthcare management based on analyses of the time lag between telenursing calls with the chief complaints (cough by adult or fever by adult) and COVID-19 hospitalization. The complaint cough by adult showed satisfactory performance (Pearson correlation coefficient r>0.80; mean absolute percentage error <20%) in nowcasting the incidence of daily COVID-19 hospitalizations 14 days in advance until the incidence decreased to <1.5/100,000 population, whereas the corresponding performance for fever by adult was unsatisfactory. Our results support local nowcasting of hospitalizations on the basis of symptom data recorded in routine healthcare during the initial stage of a pandemic. © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved.
|
|
36. |
- Trovik, Clement, et al.
(author)
-
The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma
- 2017
-
In: Acta Orthopaedica. - : TAYLOR & FRANCIS LTD. - 1745-3674 .- 1745-3682. ; 88:3, s. 341-347
-
Journal article (peer-reviewed)abstract
- Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.
|
|
37. |
- Uhlén, Mathias, et al.
(author)
-
A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
-
In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
-
Journal article (peer-reviewed)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
|
|
38. |
- Wegrzyniak, Olivia, et al.
(author)
-
Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule
- 2024
-
In: iScience. - : Elsevier. - 2589-0042. ; 27:5
-
Journal article (peer-reviewed)abstract
- Non-invasive assessment of fibrogenic activity, rather than fibrotic scars, could significantly improve the management of fibrotic diseases and the development of anti-fibrotic drugs. This study explores the potential of an Affibody molecule (Z09591) labeled with the Al(18)F-restrained complexing agent (RESCA) method as a tracer for the non-invasive detection of fibrogenic cells. Z09591 was functionalized with the RESCA chelator for direct labeling with [18F]AlF. 18 F]AlF. In vivo positron emission tomography/magnetic resonance imaging scans on U-87 tumor-bearing mice exhibited high selectivity of the resulting radiotracer, [18F]AlF-RESCA-Z09591, 18 F]AlF-RESCA-Z09591, for platelet-derived growth factor receptor b (PDGFRb), b ), with minimal non-specific background uptake. Evaluation in a mouse model with carbon tetrachloride-induced fibrotic liver followed by a disease regression phase, revealed the radiotracer's high affinity and specificity for fibrogenic cells in fibrotic livers (standardized uptake value [SUV] 0.43 +/- 0.05), with uptake decreasing during recovery (SUV 0.29 +/- 0.03) (p p < 0.0001). [18F]AlF-RESCA-Z09591 18 F]AlF-RESCA-Z09591 accurately detects PDGFRb, b, offering noninvasive assessment of fibrogenic cells and promising applications in precise liver fibrogenesis diagnosis, potentially contributing significantly to anti-fibrotic drug development.
|
|
39. |
- Wegrzyniak, Olivia, et al.
(author)
-
Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule
- 2024
-
In: iScience. - : Elsevier BV. - 2589-0042. ; 27:5
-
Journal article (peer-reviewed)abstract
- Non-invasive assessment of fibrogenic activity, rather than fibrotic scars, could significantly improve the management of fibrotic diseases and the development of anti-fibrotic drugs. This study explores the potential of an Affibody molecule (Z09591) labeled with the Al(18)F-restrained complexing agent (RESCA) method as a tracer for the non-invasive detection of fibrogenic cells. Z09591 was functionalized with the RESCA chelator for direct labeling with [18F]AlF. 18 F]AlF. In vivo positron emission tomography/magnetic resonance imaging scans on U-87 tumor-bearing mice exhibited high selectivity of the resulting radiotracer, [18F]AlF-RESCA-Z09591, 18 F]AlF-RESCA-Z09591, for platelet-derived growth factor receptor b (PDGFRb), b ), with minimal non-specific background uptake. Evaluation in a mouse model with carbon tetrachloride-induced fibrotic liver followed by a disease regression phase, revealed the radiotracer's high affinity and specificity for fibrogenic cells in fibrotic livers (standardized uptake value [SUV] 0.43 +/- 0.05), with uptake decreasing during recovery (SUV 0.29 +/- 0.03) (p p < 0.0001). [18F]AlF-RESCA-Z09591 18 F]AlF-RESCA-Z09591 accurately detects PDGFRb, b, offering noninvasive assessment of fibrogenic cells and promising applications in precise liver fibrogenesis diagnosis, potentially contributing significantly to anti-fibrotic drug development.
|
|
40. |
- Wiklund, Fredrik E, et al.
(author)
-
Macrophage inhibitory cytokine-1 (MIC-1/GDF15) : a new marker of all-cause mortality
- 2010
-
In: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 9:6, s. 1057-1064
-
Journal article (peer-reviewed)abstract
- Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a member of the TGF-b superfamily, previously studied in cancer and inflammation. In addition to regulating body weight, MIC-1/GDF15 may be used to predict mortality and/or disease course in cancer, cardiovascular disease (CVD), chronic renal and heart failure, as well as pulmonary embolism. These data suggested that MIC-1/GDF15 may be a marker of all-cause mortality. To determine whether serum MIC-1/GDF15 estimation is a predictor of all-cause mortality, we examined a cohort of 876 male subjects aged 35-80 years, selected from the Swedish Population Registry, and followed them for overall mortality. Serum MIC-1/GDF15 levels were determined for all subjects from samples taken at study entry. A second (independent) cohort of 324 same-sex twins (69% female) from the Swedish Twin Registry was similarly examined. All the twins had telomere length measured and 183 had serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) available. Patients were followed for up to 14 years and had cause-specific and all-cause mortality determined. Serum MIC-1/GDF15 levels predicted mortality in the all-male cohort with an adjusted odds ratio (OR) of death of 3.38 (95%CI 1.38-8.26). This finding was validated in the twin cohort. Serum MIC-1/GDF15 remained an independent predictor of mortality when further adjusted for telomere length, IL-6 and CRP. Additionally, serum MIC-1/GDF15 levels were directly correlated with survival time independently of genetic background. Serum MIC-1/GDF15 is a novel predictor of all-cause mortality.
|
|
41. |
- Åberg, Veronica, 1976-, et al.
(author)
-
Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of A beta-peptide aggregation inhibitors
- 2005
-
In: Organic and biomolecular chemistry. - London, U.K. : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 3:15, s. 2817-2823
-
Journal article (peer-reviewed)abstract
- A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on A beta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer A beta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric A beta-peptide.
|
|
42. |
- Abel, Edvard, 1970, et al.
(author)
-
Fatigue in Patients With Head and Neck Cancer Treated With Radiation Therapy: A Prospective Study of Patient-Reported Outcomes and Their Association With Radiation Dose to the Cerebellum
- 2022
-
In: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 7:5
-
Journal article (peer-reviewed)abstract
- Purpose: Although fatigue is a known side effect in patients with head and neck cancer (HNC) receiving radiation therapy, knowledge regarding long-term fatigue and dose-response relationships to organs at risk is scarce. The aim of this prospective study was to analyze patient-reported fatigue in patients with HNC receiving radiation therapy and to explore any possible association with organ-at-risk doses. Methods and Materials: Patients with HNC referred for curative radiation therapy were eligible for inclusion in the study. To assess patient-reported fatigue, quality of life questionnaires (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-FA12) were distributed before treatment and 1, 3, 6, 12, 24, and 60 months after the start of treatment. Mean dose (Dmean) and near maximum dose (D2%) of the cerebellum and brain stem were evaluated in relation to baseline-adjusted fatigue scores at 3 months. Results: One hundred twenty-six patients treated with intensity modulated radiation therapy between 2008 and 2010 were available for final analysis. Female sex and age <60 years were associated with higher fatigue at baseline, whereas patients also treated with chemotherapy had reduced physical and emotional fatigue at 6 months. Physical fatigue (QLQ-FA12 scale) increased from baseline up to 3 months (29 vs 59; P < .0001) but showed no difference compared with baseline from 1 to 5 years. Emotional fatigue was significantly lower at 5 years compared with baseline (14 vs 28; P < .0001). Patients with cerebellum Dmean > 3.5 Gy had higher mean physical fatigue scores at 3 months (38 vs 27; P = .036). Conclusions: Although there is a significant increase in fatigue scores for patients with HNC up to 1 year after radiation therapy, this study showed a return to baseline levels at 5 years. A possible association was found between physical fatigue and a higher mean dose to the cerebellum.
|
|
43. |
|
|
44. |
- Adams, Mike, et al.
(author)
-
Managing policy lapse risk in Sweden's life insurance market between 1915 and 1947
- 2020
-
In: Business History. - : Routledge. - 0007-6791 .- 1743-7938. ; 62:2, s. 222-239
-
Journal article (peer-reviewed)abstract
- We examine the challenges that Swedish life insurers faced in managing the lapse risk of policies written on the lives of the industrial urban working class between 1915 and 1947. We observe that with the threat of State socialisation of insurance in the 1930s, industrial life insurers modified their business practices to better control policy lapses. Using firm-level data, we also analyse the effect of socio-economic changes, such as rising real wages, interest rate fluctuations and unemployment on life insurance policy lapses. Our results support contemporary tests of the emergency fund and interest rate explanations for the voluntary premature termination of life insurance policies.
|
|
45. |
- Adjei, Evans, et al.
(author)
-
Regional labour market effects of immigration on low-skilled workers: the case of Sweden 1990–2003
- 2021
-
In: International Journal of Social Economics. - : Emerald Group Publishing Limited. - 0306-8293 .- 1758-6712. ; 48:3, s. 456-476
-
Journal article (peer-reviewed)abstract
- Purpose: The purpose of this paper is to examine the effects of immigration on the labour market outcomes of low-educated natives (i.e. residents without a university diploma). Using the labour market competition theory, which argues that the labour market effects of natives depend on the skill set of immigrants, the paper addresses whether immigrants are complementary to or substitutes for native workers.Design/methodology/approach: Longitudinal matched employer–employee data on Sweden are used to estimate how low-educated natives, in regions experiencing the greatest influx of refugees from the Balkan wars, responded to this supply shock with regard to real wages, employment and job mobility between 1990 and 2003.Findings: First, the analysis shows that low-educated native workers respond to the arrival of immigrants with an increase in real wages. Second, although employment prospects in general worsened for low-skilled workers in most regions, this is not attributable to the regions experiencing the largest supply shock. Third, there are indications that low-skilled natives in immigration-rich regions are more likely to change workplace, particularly in combination with moving upwards in the wage distribution.Originality/value: Rather than seeing an emergence of the commonly perceived displacement mechanism when an economy is subject to a supply shock, the regional findings suggest that high inflows of immigrants tend to induce a mechanism that pulls native workers upwards in the wage distribution. This is important, as the proportion of immigrants is seldom evenly distributed within a nation.
|
|
46. |
- Agrell, Fredrik, et al.
(author)
-
Control of HCCI During Engine Transients by aid of Variable Valve Timings Through the use of Model Based Non-Linear Compensation
- 2005
-
In: SAE transactions. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0096-736X. ; 114:3, s. 296-310
-
Journal article (peer-reviewed)abstract
- One of the main challenges with the Homogeneous Charge Compression Ignition, HCCI, combustion system is to control the Start Of Combustion, SOC, for varying load and external conditions. A method to achieve this on a cycle-by-cycle basis is to vary the valve timing based on a feedback signal from the SOC of previous cycles. The control can be achieved with two basic valve-timing strategies named the Overlap- and the IVC-method. The Overlap-method works by trapping of residuals while the IVC-method affects the effective compression ratio. In an earlier paper it has been shown that if the two methods are incorporated into one controller, SOC can be controlled in a relatively large operating window although the transient performance was not sufficient. The reason is that the simple PI-controller cannot be made fast enough to cope with the transients without magnifying the cycle-to-cycle variations of the combustion into instability. In this work a model based control system that features a non-linear compensation, based on the inverse of the non-linear function from valve timings to ignition delay, is suggested and evaluated. The results show good transient performance. Control performance from engine tests is reported. A combined engine and control simulation system is used for the development of the control strategies. The simulations are accomplished with a commercial cycle simulation code linked with a commercial control simulation code. The simulations are iteratively verified against engine test data. Engine tests are conducted on a single cylinder engine equipped with a hydraulic valve system.
|
|
47. |
|
|
48. |
|
|
49. |
|
|
50. |
- Agrell, Fredrik, et al.
(author)
-
Transient Control of HCCI Through Combined Intake and Exhaust Valve Actuation
- 2003
-
Conference paper (peer-reviewed)abstract
- Homogeneous Charge Compression Ignition, HCCI, has the attractive feature of low particulate emission and low Nitrogen Oxides, NOx, emission combined with high efficiency. The principle is a combination of an Otto and a Diesel engine in that a premixed charge is ignited by the compression heat.
|
|