| 1. |
- Ademuyiwa, Adesoji O., et al.
(author)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Bjerg, Anders, et al.
(author)
-
Shorter time to clinical decision in work-related asthma using a digital tool
- 2020
-
In: ERJ open research. - Lausanne, Switzerland : European Respiratory Society (ERS). - 2312-0541. ; 6:3
-
Journal article (other academic/artistic)abstract
- PEF curves are a useful but cumbersome tool in diagnosing work-related asthma. Using a digital spirometer and smartphone app, time to clinical decision could be shortened by 6-7 weeks. Physician's time spent analysing PEF data is also shortened.
|
|
| 5. |
- Shalom, Jonathan G., et al.
(author)
-
Mediation of social anxiety and depression during internet-delivered treatment for social anxiety disorder
- 2024
-
In: Cognitive Behaviour Therapy. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 1650-6073 .- 1651-2316.
-
Journal article (peer-reviewed)abstract
- Many individuals with social anxiety disorder (SAD) have depressive symptoms that meet criteria for major depressive disorder (MDD). In our study, we examined the temporal relationship between symptoms of social anxiety and symptoms of depression during the course of an 11-week internet-delivered cognitive behavioral treatment (ICBT) for SAD (n = 170). Specifically, we investigated whether weekly changes in social anxiety mediated changes in depression, changes in depression mediated changes in anxiety, both or neither. In addition, we compared individuals with SAD and MDD (n = 50) and individuals with SAD and no MDD (n = 120) to examine the role of MDD as a moderator of the social anxiety-depression relationship. Lower-level mediational modeling revealed that changes in social anxiety symptoms mediated changes in depression symptoms to a greater extent than vice versa. In addition, mediation among individuals with SAD and MDD was significantly greater compared to individuals with SAD and no MDD. Our findings suggest that ICBT is effective in treating individuals with SAD regardless of comorbid depression, and that focusing ICBT interventions on social anxiety can lead to significant reductions in depression among individuals with SAD.
|
|
| 6. |
- Shalom, Jonathan G, et al.
(author)
-
Predicting sudden gains before treatment begins : An examination of pretreatment intraindividual variability in symptoms.
- 2020
-
In: Journal of Consulting and Clinical Psychology. - : American Psychological Association (APA). - 0022-006X .- 1939-2117. ; 88:9, s. 809-817
-
Journal article (peer-reviewed)abstract
- Objective: Sudden gains during psychotherapy have been found to be predictive of positive treatment outcomes. Previous attempts at predicting occurrence of sudden gains have yielded equivocal findings. Recently, intraindividual variability in symptoms during treatment was suggested as a trans-therapeutic and trans-diagnostic predictor of sudden gains. The goal of the present study was to examine this predictor in Internet-delivered treatment for social anxiety disorder (SAD) and to examine whether this predictor predicts sudden gains when measured before treatment begins. Method: We examined data from a preregistered randomized controlled trial (RCT) of Internet-delivered cognitive-behavioral therapy (CBT) for SAD (n = 101). We measured variability in symptoms both within-treatment and before treatment (i.e. during waitlist). Results: Intraindividual variability in symptoms significantly predicted sudden gains both when measured before treatment or within-treatment and correctly classified 84% and 83% of individuals to sudden gains versus non-sudden gains status, respectively. Conclusions: Intraindividual variability in symptoms can predict sudden gains in Internet-delivered treatment for SAD, thus supporting its trans-diagnostic and trans-therapeutic nature. Predicting sudden gains before treatment begins has implications for treatment planning and clinical decision making as well as for personalized tailoring of interventions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
|
|
| 7. |
- Al-Saadi, Jonathan, et al.
(author)
-
Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart
- 2024
-
In: Molecular therapy. Methods & clinical development. - : Elsevier BV. - 2399-6951 .- 2329-0501. ; 32:2
-
Journal article (peer-reviewed)abstract
- Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.
|
|
| 8. |
- Aldridge, Jonathan, et al.
(author)
-
Blood chemokine levels are markers of disease activity but not predictors of remission in early rheumatoid arthritis.
- 2022
-
In: Clinical and experimental rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 40:7, s. 1393-1402
-
Journal article (peer-reviewed)abstract
- In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated eRA.This study included 347 Swedish patients with untreated eRA from the larger NORD-STAR randomised treatment trial. Here, eRA patients were treated with methotrexate combined with either prednisolone, anti-TNF (certolizumab-pegol), CTLA-4Ig (abatacept) or anti-IL6 receptor (tocilizumab). The primary clinical outcome was remission by clinical disease activity index (CDAI) defined as CDAI ≤ 2.8. Disease activity was assessed by CDAI, DAS28-ESR, DAS28-CRP, swollen joint counts, tender joint counts, ESR and CRP. The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or ELISA.Baseline plasma concentrations of CXCL10, CXCL8, CXCL9, CXCL11, CXCL5 and CCL2 correlated with baseline disease activity measures. After 24 weeks of treatment, plasma levels of CXCL10, CXCL8, CXCL9, CXCL11 and CXCL13 decreased in all treatment groups except in patients treated with anti-IL6 receptor. In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups.In patients with untreated eRA, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti‑TNF, CTLA‑4Ig or anti‑IL6R.
|
|
| 9. |
- Aldridge, Jonathan, et al.
(author)
-
Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis.
- 2022
-
In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:3, s. 1233-1242
-
Journal article (peer-reviewed)abstract
- Treatment with CTLA-4Ig blocks T cell activation and is clinically effective in rheumatoid arthritis (RA). However, it is unknown if specific CD4+ T cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4+ T cells in patients with untreated early RA (eRA).This study included 60 patients with untreated eRA from a larger randomised trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n=17), anti-IL6 receptor (tocilizumab, n=21) or anti-TNF (certolizumab-pegol, n=22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI≤2.8) at week 24. Proportions of 12 CD4+ T cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24weeks of treatment.In patients treated with CTLA-4Ig, the proportions of PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline predicted CDAI remission at week 24. CD4+ T cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1+T follicular helper (TFh) cells.These findings indicate that circulating proportions PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.
|
|
| 10. |
- Aldridge, Jonathan, et al.
(author)
-
Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients
- 2018
-
In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
-
Journal article (peer-reviewed)abstract
- Background: It is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA). Hence, we examined whether circulating T cell subset proportions and their association with disease activity differed in male and female patients with untreated early rheumatoid arthritis (ueRA). Methods: Proportions of T cell subsets were analyzed in peripheral blood from 72 ueRA DMARD-and corticosteroid-naive patients (50 females and 22 males) and in 31 healthy age-and sex-matched controls. Broad analysis of helper and regulatory CD4(+) T cell subsets was done using flow cytometry. Disease activity in patients was assessed using DAS28, CDAI, swollen joint counts, tender joint counts, CRP, and ESR. Results: Multivariate factor analyses showed that male and female ueRA patients display distinct profiles of association between disease activity and circulating T cell subset proportions. In male, but not female, ueRA patients Th2 cells showed a positive association with disease activity and correlated significantly with DAS28-ESR, CDAI, and swollen and tender joint counts. Likewise, proportions of non-regulatory CTLA-4(+) T cells associated positively with disease activity in male patients only, and correlated with DAS28-ESR. In contrast, there was a negative relation between Th1Th17 subset proportions and disease activity in males only. The proportions of Th17 cells correlated positively with DAS28-ESR in males only, while proportions of Th1 cells showed no relation to disease activity in either sex. There were no significant differences in proportions of T cell subsets between the sexes in patients with ueRA. Conclusions: Our findings show sex-based differences in the association between T cell subsets and disease activity in ueRA patients, and that Th2 helper T cells may have a role in regulating disease activity in male patients.
|
|
| 11. |
- Aldridge, Jonathan, et al.
(author)
-
T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3(+)Th2 phenotype
- 2020
-
In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
-
Journal article (peer-reviewed)abstract
- Background The majority of CD4(+)T helper (Th) cells found in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) express CXCR3, a receptor associated with Th1 cells. In blood, subsets of Th2 and Th17 cells also express CXCR3, but it is unknown if these cells are present in RA SF or how cytokines from these subsets affect cytokine/chemokine secretion by fibroblast-like synoviocytes (FLS) from patients with RA. Methods We examined the proportions of Th1, Th2, CXCR3(+)Th2, Th17, CXCR3(+)Th17, Th1Th17, peripheral T helper (TPh) and T follicular helper (TFh) cells in paired SF and blood, as well as the phenotype of TPh and TFh cells in RA SF (n = 8), by the use of flow cytometry. We also examined the cytokine/chemokine profile in paired SF and plasma (n = 8) and in culture supernatants of FLS from patients with chronic RA (n = 7) stimulated with Th-associated cytokines, by the use of cytometric bead arrays and ELISA. Cytokine receptor expression in FLS (n = 3) were assessed by the use of RNA sequencing and qPCR. Results The proportions of Th1 and CXCR3(+)Th2 cells were higher in SF than in blood (P < 0.05). TPh and PD-1(high)TFh in RA SF were primarily of a Th1 and a CXCR3(+)Th2 phenotype. Moreover, the levels of CXCL9, CXCL10, CCL20, CCL2, CXCL8, IL-6 and IL-10 were higher in SF than in plasma (P < 0.05). Lastly, IL-4, IL-13 and IL-17A induced RA FLS to secrete proinflammatory IL-6, CCL2, CXCL1 and CXCL8, while IFN gamma mainly induced CXCL10. Conclusion These findings indicate that not only Th1 but also CXCR3(+)Th2 cells may have a pathogenic role in RA synovial inflammation.
|
|
| 12. |
- Allsopp, Benjamin, et al.
(author)
-
Towards improved cover glasses for photovoltaic devices
- 2020
-
In: Progress in Photovoltaics. - : John Wiley and Sons Ltd. - 1062-7995 .- 1099-159X. ; 28, s. 1187-1206
-
Journal article (peer-reviewed)abstract
- For the solar energy industry to increase its competitiveness, there is a global drive to lower the cost of solar-generated electricity. Photovoltaic (PV) module assembly is material-demanding, and the cover glass constitutes a significant proportion of the cost. Currently, 3-mm-thick glass is the predominant cover material for PV modules, accounting for 10%–25% of the total cost. Here, we review the state-of-the-art of cover glasses for PV modules and present our recent results for improvement of the glass. These improvements were demonstrated in terms of mechanical, chemical and optical properties by optimizing the glass composition, including addition of novel dopants, to produce cover glasses that can provide (i) enhanced UV protection of polymeric PV module components, potentially increasing module service lifetimes; (ii) re-emission of a proportion of the absorbed UV photon energy as visible photons capable of being absorbed by the solar cells, thereby increasing PV module efficiencies and (iii) successful laboratory-scale demonstration of proof of concept, with increases of 1%–6% in Isc and 1%–8% in Ipm. Improvements in both chemical and crack resistance of the cover glass were also achieved through modest chemical reformulation, highlighting what may be achievable within existing manufacturing technology constraints. © 2020 The Authors.
|
|
| 13. |
|
|
| 14. |
- Alvarsson, Jonathan, et al.
(author)
-
Benchmarking Study of Parameter Variation When Using Signature Fingerprints Together with Support Vector Machines
- 2014
-
In: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 54:11, s. 3211-3217
-
Journal article (peer-reviewed)abstract
- QSAR modeling using molecular signatures and support vector machines with a radial basis function is increasingly used for virtual screening in the drug discovery field. This method has three free parameters: C, ?, and signature height. C is a penalty parameter that limits overfitting, ? controls the width of the radial basis function kernel, and the signature height determines how much of the molecule is described by each atom signature. Determination of optimal values for these parameters is time-consuming. Good default values could therefore save considerable computational cost. The goal of this project was to investigate whether such default values could be found by using seven public QSAR data sets spanning a wide range of end points and using both a bit version and a count version of the molecular signatures. On the basis of the experiments performed, we recommend a parameter set of heights 0 to 2 for the count version of the signature fingerprints and heights 0 to 3 for the bit version. These are in combination with a support vector machine using C in the range of 1 to 100 and gamma in the range of 0.001 to 0.1. When data sets are small or longer run times are not a problem, then there is reason to consider the addition of height 3 to the count fingerprint and a wider grid search. However, marked improvements should not be expected.
|
|
| 15. |
- Alvarsson, Jonathan, et al.
(author)
-
Brunn : an open source laboratory information system for microplates with a graphical plate layout design process
- 2011
-
In: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 12:1
-
Journal article (peer-reviewed)abstract
- Background:Compound profiling and drug screening generates large amounts of data and is generally based on microplate assays. Current information systems used for handling this are mainly commercial, closed source, expensive, and heavyweight and there is a need for a flexible lightweight open system for handling plate design, and validation and preparation of data.Results:A Bioclipse plugin consisting of a client part and a relational database was constructed. A multiple-step plate layout point-and-click interface was implemented inside Bioclipse. The system contains a data validation step, where outliers can be removed, and finally a plate report with all relevant calculated data, including dose-response curves.Conclusions:Brunn is capable of handling the data from microplate assays. It can create dose-response curves and calculate IC50 values. Using a system of this sort facilitates work in the laboratory. Being able to reuse already constructed plates and plate layouts by starting out from an earlier step in the plate layout design process saves time and cuts down on error sources.
|
|
| 16. |
- Alvarsson, Jonathan, et al.
(author)
-
Large-scale ligand-based predictive modelling using support vector machines
- 2016
-
In: Journal of Cheminformatics. - : Springer Science and Business Media LLC. - 1758-2946. ; 8
-
Journal article (peer-reviewed)abstract
- The increasing size of datasets in drug discovery makes it challenging to build robust and accurate predictive models within a reasonable amount of time. In order to investigate the effect of dataset sizes on predictive performance and modelling time, ligand-based regression models were trained on open datasets of varying sizes of up to 1.2 million chemical structures. For modelling, two implementations of support vector machines (SVM) were used. Chemical structures were described by the signatures molecular descriptor. Results showed that for the larger datasets, the LIBLINEAR SVM implementation performed on par with the well-established libsvm with a radial basis function kernel, but with dramatically less time for model building even on modest computer resources. Using a non-linear kernel proved to be infeasible for large data sizes, even with substantial computational resources on a computer cluster. To deploy the resulting models, we extended the Bioclipse decision support framework to support models from LIBLINEAR and made our models of logD and solubility available from within Bioclipse.
|
|
| 17. |
- Alvarsson, Jonathan, 1981-
(author)
-
Ligand-based Methods for Data Management and Modelling
- 2015
-
Doctoral thesis (other academic/artistic)abstract
- Drug discovery is a complicated and expensive process in the billion dollar range. One way of making the drug development process more efficient is better information handling, modelling and visualisation. The majority of todays drugs are small molecules, which interact with drug targets to cause an effect. Since the 1980s large amounts of compounds have been systematically tested by robots in so called high-throughput screening. Ligand-based drug discovery is based on modelling drug molecules. In the field known as Quantitative Structure–Activity Relationship (QSAR) molecules are described by molecular descriptors which are used for building mathematical models. Based on these models molecular properties can be predicted and using the molecular descriptors molecules can be compared for, e.g., similarity. Bioclipse is a workbench for the life sciences which provides ligand-based tools through a point and click interface. The aims of this thesis were to research, and develop new or improved ligand-based methods and open source software, and to work towards making these tools available for users through the Bioclipse workbench. To this end, a series of molecular signature studies was done and various Bioclipse plugins were developed.An introduction to the field is provided in the thesis summary which is followed by five research papers. Paper I describes the Bioclipse 2 software and the Bioclipse scripting language. In Paper II the laboratory information system Brunn for supporting work with dose-response studies on microtiter plates is described. In Paper III the creation of a molecular fingerprint based on the molecular signature descriptor is presented and the new fingerprints are evaluated for target prediction and found to perform on par with industrial standard commercial molecular fingerprints. In Paper IV the effect of different parameter choices when using the signature fingerprint together with support vector machines (SVM) using the radial basis function (RBF) kernel is explored and reasonable default values are found. In Paper V the performance of SVM based QSAR using large datasets with the molecular signature descriptor is studied, and a QSAR model based on 1.2 million substances is created and made available from the Bioclipse workbench.
|
|
| 18. |
- Andersson, Björn, et al.
(author)
-
Aggressiveness of Phytophthora infestans on detached potato leaflets in four Nordic countries
- 2009
-
In: Plant Pathology. - : Wiley. - 0032-0862 .- 1365-3059. ; 58, s. 690-702
-
Journal article (peer-reviewed)abstract
- Potato fields in Denmark, Finland, Norway and Sweden were sampled for single-lesion isolates of Phytophthora infestans. The aggressiveness of the isolates was determined on detached leaflets of potato cvs Bintje (susceptible) and Matilda (moderately resistant). The aggressiveness tests were carried out in the respective home countries of the isolates, with the exception of the Danish isolates. Fifteen Danish isolates were studied in each of the other three countries, including five isolates tested in all three laboratories. Results obtained from the Danish isolates revealed substantial differences between the test laboratories for infection efficiency, lesion growth rate and sporulation capacity on detached leaflets. When the laboratory effect was taken into account, the differences in aggressiveness between the countries were generally small or inconsistent between the test cultivars and epidemiologically insignificant. By contrast, variation among isolates within countries was substantial. The magnitude of the variation depended on country and cultivar. Maximal variation for the means of the isolates was between 89 and 185 h for latent period, between 100 and 1297 sporangia mm−2 for sporulation capacity and between nearly zero and 6 mm day−1 for lesion growth rate. Typically less than 1% of sporangia were able to cause infections, except in Norway. These extraordinarily low values may be an artefact of the testing method. High variation in results between the test laboratories emphasizes the need for caution when comparing results obtained by different research groups
|
|
| 19. |
- Andersson, Björn, et al.
(author)
-
Genetic analysis of Phytophthora infestans populations in the Nordic European countries reveals high genetic variability
- 2011
-
In: Fungal Biology. - : Elsevier BV. - 1878-6146. ; 115, s. 335-342
-
Journal article (peer-reviewed)abstract
- Late blight, caused by the oomycete Phytophthora infestans, is the most important disease of potato (Solanum tuberosum). The pathogen is highly adaptable and to get an overview of the genetic variation in the Nordic countries, Denmark, Finland, Norway and Sweden we have analyzed 200 isolates from different fields using nine simple-sequence repeat (SSR) markers. Forty-nine alleles were detected among the nine SSR loci and isolates from all four Nordic countries shared the most common alleles across the loci. In total 169 multi-locus genotypes (based on seven loci) were identified among 191 isolates. The genotypic diversities, quantified by a normalized Shannon's diversity index (H(s)), were 0.95 for the four Nordic countries. The low F(ST) value of 0.04 indicates that the majority of variation is found within the four Nordic countries. The large number of genotypes and the frequency distribution of mating types (60% A1) support the hypothesis that sexual reproduction is contributing notably to the genetic variation of P. infestans in the Nordic countries. (C) 2011 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
|
|
| 20. |
|
|
| 21. |
- Andersson, Björn, et al.
(author)
-
The Role of Oospores in the Epidemiology of Potato Late Blight
- 2009
-
In: Acta Horticulturae. - 0567-7572 .- 2406-6168. ; 834, s. 61-68
-
Conference paper (other academic/artistic)abstract
- Potato late blight (Phytophthora infestans) is a plant disease feared globally by farmers and the potato industry. P. infestans is a heterothallic oomycete with two mating types. Until recently the pathogen was limited to surviving between seasons as living mycelia in its host plant in most parts of the world. This was due to the fact that populations of P. infestans consisted of only one mating type (A1) in all parts of the world except Mexico, the putative centre of origin of the pathogen. Migration of new genotypes from Mexico, including genotypes of the second mating type (A2) has resulted in that now both mating types can be found worldwide. The formation of oospores is only possible if both mating types coexist. Oospores will give the pathogen the ability of surviving for extended periods of time outside its host, for example in the soil. There are reports of oospore formation under field conditions from many parts of the world. Also, in some places oospores are considered as a new, additional inoculum source and as a consequence the onset of late blight epidemics have become earlier. Oospores are formed through sexual recombination. If they act as a source of inoculum, this will increase the genotypic variation in populations of P. infestans leading to an enhanced adaptability of the pathogen. As a consequence, an earlier start of epidemics caused by oospores in the soil and a more aggressive behaviour of the pathogen due to new sexually formed genotypes could make potato late blight even more difficult to control in the future.
|
|
| 22. |
|
|
| 23. |
- Andersson, Christoffer, et al.
(author)
-
Infrastructuring for remote night monitoring : Frictions in striving for transparency when digitalising care service
- 2018
-
In: ECSCW 2018 - Proceedings of the 16th European Conference on Computer Supported Cooperative Work. - : Springer.
-
Conference paper (peer-reviewed)abstract
- The question of how to organise for the introduction of a new service involving the interaction of humans and technologies is both crucial and challenging. Convergence between the community of practice using the technology and the design of the technology is crucial for the technology to become meaningful and usable. While processes of convergence are challenging in themselves, they become more complex if several communities of practice are going to use and collaborate around/through the technology. The co-presence of different communities of practice is a common situation when delivering public welfare services. In particular, the development of welfare technology is a context rich in potential frictions, making convergence challenging. By mobilising the concept of transparency, we analyse the process of implementation of remote night monitoring and highlight how transparency is related to different aspects. Such analysis reveals that processes of convergence are related in this context not only to frictions shared with other settings, but also to specific frictions related to matters of concern in welfare services. This leads us to discuss whether digitalised care services can be argued as still having a human side or not.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Andersson, Daniel, 1964, et al.
(author)
-
Judisk Mosaik Introduktion till judisk religion, kultur och tradition
- 2008
-
Book (other academic/artistic)abstract
- Boken ger en tematisk och historisk översikt av judendom och judisk identitet som speglar mångfalden i traditionen, mystiken och filosofin. Med grund i ett omfattande intervjumaterial förmedlar den svenska judars livshistorier och perspektiv på exempelvis global judendom, självuppfattning och religion.
|
|
| 27. |
|
|
| 28. |
- Andersson, Jonathan, 1992-
(author)
-
Bifurcations and Exchange of Stability with Density Dependence in a Coinfection Model and an Age-structured Population Model
- 2022
-
Doctoral thesis (other academic/artistic)abstract
- In nature many pathogens and in particular strains of pathogens with negative effects on species coexists. This is for simplicity often ignored in many epidemiological models. It is however still of interest to get a deeper understanding how this coexistence affects the dynamics of the disease. There are several ways at which coexistence can influence the dynamics. Coinfection which is the simultaneous infection of two or more pathogens can cause increased detrimental health effects on the host. Pathogens can also limit each others growth by the effect of cross immunity as well as promoting isolation. On the contrary one pathogen can also aid another by making the host more vulnerable to as well as more inclined to spread disease.Spread of disease is dependent on the density of the population. If a pathogen is able to spread or not, is strongly correlated with how many times individuals interact with each other. This in turn depends on how many individuals live in a given area. The aim of papers I-III is to provide an understanding how different factors including the carrying capacity of the host population affect the dynamics of two coexisting diseases. In papers I-III we investigate how the parameters effects the long term solution in the form of a stable equilibrium point. In particular we want to provide an understanding of how changes in the carrying capacity affects the long term existence of each disease as well as the occurrence of coinfection.The model that is studied in papers I-III is a generalization of the standard susceptible, infected, recovered (SIR) compartmental model. The SIR model is generalized by the introduction of the second infected compartment as well as the coinfection compartment. We also use a logistic growth term à la Verhulst with associated carrying capacity K. In paper I and II we make the simplifying assumption that a coinfected individual has to, if anything, transmit both of the disease and simply not just one of them. This restriction is relaxed in paper III. In all papers I-III however we do restrict ourselves by letting all transmission rates, that involves scenarios where the newly infected person does not move to same compartment as the infector, to be small. By small we here mean that the results at least hold when the relevant parameters are small enough.In all paper I-III it turns out that for each set of parameters excluding K there exist a unique branch of mostly stable equilibrium points depending continuously on K. We differentiate the equilibrium points of the branch by which compartments are non-zero which we refer to as the type of the equilibrium. The way that the equilibrium point changes its type with K is made clear with the use of transition diagrams together with graphs for the stable susceptible population over K.In paper IV we consider a model for a single age-structured population á la Mckendric-von-Foerster with the addition of differing density dependence on the birth and death rates. Each vital rate is a function of age as well as a weighing of the population also referred to as a size. The birth rate influencing size and the death rate influencing size can be weighted differently allowing us to consider different age-groups to influence the birth and death rate in different proportions compared to other age groups. It is commonly assumed that an increase of population density is detrimental to the survival of each individual. However, for various reasons, it is know that for some species survival is positively correlated with population density when the population is small. This is called the Allee effect and our model includes this scenario.It is shown that the trivial equilibrium, which signifies extinction, is locally stable if the basic reproductive rate $R_0$ is less then 1. This implies global stability with certain extinction if no Allee effect is present. However if the Allee effect is present we show that the population can persist even if R0 < 1.
|
|
| 29. |
- Andersson, Jonathan, et al.
(author)
-
Density-Dependent Feedback in Age-Structured Populations
- 2019
-
In: Journal of Mathematical Sciences. - : Springer Berlin/Heidelberg. - 1072-3374 .- 1573-8795. ; 242:1, s. 2-24
-
Journal article (peer-reviewed)abstract
- The population size has far-reaching effects on the fitness of the population, that, in its turn influences the population extinction or persistence. Understanding the density- and age-dependent factors will facilitate more accurate predictions about the population dynamics and its asymptotic behaviour. In this paper, we develop a rigourous mathematical analysis to study positive and negative effects of increased population density in the classical nonlinear age-structured population model introduced by Gurtin \& MacCamy in the late 1970s. One of our main results expresses the global stability of the system in terms of the newborn function only. We also derive the existence of a threshold population size implying the population extinction, which is well-known in population dynamics as an Allee effect.
|
|
| 30. |
- Andersson, Jonathan, et al.
(author)
-
Effect of density dependence on coinfection dynamics
- 2021
-
In: Analysis and Mathematical Physics. - Basel, Switzerland : Birkhaeuser Science. - 1664-2368 .- 1664-235X. ; 11:4
-
Journal article (peer-reviewed)abstract
- In this paper we develop a compartmental model of SIR type (the abbreviation refers to the number of Susceptible, Infected and Recovered people) that models the population dynamics of two diseases that can coinfect. We discuss how the underlying dynamics depends on the carrying capacity K: from a simple dynamics to a more complex. This can also help in understanding the appearance of more complicated dynamics, for example, chaos and periodic oscillations, for large values of K. It is also presented that pathogens can invade in population and their invasion depends on the carrying capacity K which shows that the progression of disease in population depends on carrying capacity. More specifically, we establish all possible scenarios (the so-called transition diagrams) describing an evolution of an (always unique) locally stable equilibrium state (with only non-negative compartments) for fixed fundamental parameters (density independent transmission and vital rates) as a function of the carrying capacity K. An important implication of our results is the following important observation. Note that one can regard the value of K as the natural ‘size’ (the capacity) of a habitat. From this point of view, an isolation of individuals (the strategy which showed its efficiency for COVID-19 in various countries) into smaller resp. larger groups can be modelled by smaller resp. bigger values of K. Then we conclude that the infection dynamics becomes more complex for larger groups, as it fairly maybe expected for values of the reproduction number R0≈1. We show even more, that for the values R0>1 there are several (in fact four different) distinguished scenarios where the infection complexity (the number of nonzero infected classes) arises with growing K. Our approach is based on a bifurcation analysis which allows to generalize considerably the previous Lotka-Volterra model considered previously in Ghersheen et al. (Math Meth Appl Sci 42(8), 2019).
|
|
| 31. |
- Andersson, Jonathan, et al.
(author)
-
Effect of density dependence on coinfection dynamics : part 2
- 2021
-
In: Analysis and Mathematical Physics. - : Springer Basel AG. - 1664-2368 .- 1664-235X. ; 11:4
-
Journal article (peer-reviewed)abstract
- In this paper we continue the stability analysis of the model for coinfection with density dependent susceptible population introduced in Andersson et al. (Effect of density dependence on coinfection dynamics. arXiv:2008.09987, 2020). We consider the remaining parameter values left out from Andersson et al. (Effect of density dependence on coinfection dynamics. arXiv:2008.09987, 2020). We look for coexistence equilibrium points, their stability and dependence on the carrying capacity K. Two sets of parameter value are determined, each giving rise to different scenarios for the equilibrium branch parametrized by K. In both scenarios the branch includes coexistence points implying that both coinfection and single infection of both diseases can exist together in a stable state. There are no simple explicit expression for these equilibrium points and we will require a more delicate analysis of these points with a new bifurcation technique adapted to such epidemic related problems. The first scenario is described by the branch of stable equilibrium points which includes a continuum of coexistence points starting at a bifurcation equilibrium point with zero single infection strain #1 and finishing at another bifurcation point with zero single infection strain #2. In the second scenario the branch also includes a section of coexistence equilibrium points with the same type of starting point but the branch stays inside the positive cone after this. The coexistence equilibrium points are stable at the start of the section. It stays stable as long as the product of K and the rate γ¯γ¯ of coinfection resulting from two single infections is small but, after this it can reach a Hopf bifurcation and periodic orbits will appear.
|
|
| 32. |
- Andersson, Jonathan, et al.
(author)
-
Estimating the cold-induced brown adipose tissue glucose uptake rate measured by 18F-FDG PET using infrared thermography and water-fat separated MRI
- 2019
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Journal article (peer-reviewed)abstract
- Brown adipose tissue (BAT) expends chemical energy to produce heat, which makes it a potential therapeutic target for combating metabolic dysfunction and overweight/obesity by increasing its metabolic activity. The most well-established method for measuring BAT metabolic activity is glucose uptake rate (GUR) measured using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). However, this is expensive and exposes the subjects to potentially harmful radiation. Cheaper and safer methods are warranted for large-scale or longitudinal studies. Potential alternatives include infrared thermography (IRT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate and further develop these techniques. Twelve healthy adult subjects were studied. The BAT GUR was measured using 18F-FDG PET during individualized cooling. The temperatures of the supraclavicular fossae and a control region were measured using IRT during a simple cooling protocol. The fat fraction and effective transverse relaxation rate of BAT were measured using MRI without any cooling intervention. Simple and multiple linear regressions were employed to evaluate how well the MRI and IRT measurements could estimate the GUR. Results showed that both IRT and MRI measurements correlated with the GUR. This suggest that these measurements may be suitable for estimating the cold-induced BAT GUR in future studies.
|
|
| 33. |
- Andersson, Jonathan, et al.
(author)
-
Exploring the Impact of Menu Systems, Interaction Methods, and Sitting or Standing Posture on User Experience in Virtual Reality
- 2023
-
In: 2023 IEEE Gaming, Entertainment, and Media Conference, GEM 2023. - : Institute of Electrical and Electronics Engineers (IEEE). - 9798350315400
-
Conference paper (peer-reviewed)abstract
- Virtual Reality (VR) has become an increasingly crucial aspect in both commercial and industrial settings. However, the user experience of the user interfaces and interaction methods in the VR environment is often overlooked. This paper aims to explore different menu systems, interaction methods, and the user’s sitting or standing posture on user experience and cybersickness in VR applications. An experiment with two menu systems and two interaction methods in an implemented VR application was conducted with 20 participants. The results found that traditional, top-down, panel menus with motion controls are the best combination regarding the user experience. Sitting posture provides less severe simulator sickness symptoms than standing.
|
|
| 34. |
- Andersson, Jonathan, et al.
(author)
-
MRI estimates of brown adipose tissue in children - Associations to adiposity, osteocalcin, and thigh muscle volume
- 2019
-
In: Magnetic Resonance Imaging. - : Elsevier BV. - 0730-725X .- 1873-5894. ; 58, s. 135-142
-
Journal article (peer-reviewed)abstract
- Context Brown adipose tissue is of metabolic interest. The tissue is however poorly explored in children. Methods: Sixty-three 7-year old subjects from the Swedish birth-cohort Halland Health and Growth Study were recruited. Care was taken to include both normal weight and overweight children, but the subjects were otherwise healthy. Only children born full term were included. Water-fat separated whole-body MRI scans, anthropometric measurements, and measurements of fasting glucose and levels of energy homeostasis related hormones, including the insulin-sensitizer osteocalcin, were performed. The fat fraction (FF) and effective transverse relaxation time (T-2(star)) of suspected brown adipose tissue in the cervical-supraclavicular-axillary fat depot (sBAT) and the FFs of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) were measured. Volumes of sBAT, abdominal VAT and SAT, and thigh muscle volumes were measured. Results: The FF in the sBAT depot was lower than in VAT and SAT for all children. In linear correlations including sex and age as explanatory variables, sBAT FF correlated positively with all measures of adiposity (p < 0.01), except for VAT FF and weight, positively with sBAT T-2* (p = 0.036), and negatively with osteocalcin (p = 0.017). When adding measures of adiposity as explanatory variables, sBAT FF also correlated negatively with thigh muscle volume (p < 0.01). Conclusions: Whole-body water-fat MRI of children allows for measurements of sBAT. The FF of sBAT was lower than that of VAT and SAT, indicating presence of BAT. Future studies could confirm whether the observed correlations corresponds to a hormonally active BAT.
|
|
| 35. |
- Andersson, Jonathan, et al.
(author)
-
Separation of water and fat signal in whole-body gradient echo scans using convolutional neural networks
- 2019
-
In: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 82:3, s. 1177-1186
-
Journal article (peer-reviewed)abstract
- Purpose: To perform and evaluate water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks.Methods: Whole‐body gradient echo scans of 240 subjects, each consisting of 5 bipolar echoes, were used. Reference fat fraction maps were created using a conventional method. Convolutional neural networks, more specifically 2D U‐nets, were trained using 5‐fold cross‐validation with 1 or several echoes as input, using the squared difference between the output and the reference fat fraction maps as the loss function. The outputs of the networks were assessed by the loss function, measured liver fat fractions, and visually. Training was performed using a graphics processing unit (GPU). Inference was performed using the GPU as well as a central processing unit (CPU).Results: The loss curves indicated convergence, and the final loss of the validation data decreased when using more echoes as input. The liver fat fractions could be estimated using only 1 echo, but results were improved by use of more echoes. Visual assessment found the quality of the outputs of the networks to be similar to the reference even when using only 1 echo, with slight improvements when using more echoes. Training a network took at most 28.6 h. Inference time of a whole‐body scan took at most 3.7 s using the GPU and 5.8 min using the CPU.Conclusion: It is possible to perform water–fat signal separation of whole‐body gradient echo scans using convolutional neural networks. Separation was possible using only 1 echo, although using more echoes improved the results.
|
|
| 36. |
- Andersson, Jonathan, et al.
(author)
-
Water-fat separation incorporating spatial smoothing is robust to noise
- 2018
-
In: Magnetic Resonance Imaging. - : Elsevier BV. - 0730-725X .- 1873-5894. ; 50, s. 78-83
-
Journal article (peer-reviewed)abstract
- PURPOSE: To develop and evaluate a noise-robust method for reconstruction of water and fat images for spoiled gradient multi-echo sequences.METHODS: The proposed method performs water-fat separation by using a graph cut to minimize an energy function consisting of unary and binary terms. Spatial smoothing is incorporated to increase robustness to noise. The graph cut can fail to find a solution covering the entire image, in which case the relative weighting of the unary term is iteratively increased until a complete solution is found. The proposed method was compared to two previously published methods. Reconstructions were performed on 16 cases taken from the 2012 ISMRM water-fat reconstruction challenge dataset, for which reference reconstructions were provided. Robustness towards noise was evaluated by reconstructing images with different levels of noise added. The percentage of water-fat swaps were calculated to measure performance.RESULTS: At low noise levels the proposed method produced similar results to one of the previously published methods, while outperforming the other. The proposed method significantly outperformed both of the previously published methods at moderate and high noise levels.CONCLUSION: By incorporating spatial smoothing, an increased robustness towards noise is achieved when performing water-fat reconstruction of spoiled gradient multi-echo sequences.
|
|
| 37. |
- Andersson, Jonathan
(author)
-
Water–fat separation in magnetic resonance imaging and its application in studies of brown adipose tissue
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- Virtually all the magnetic resonance imaging (MRI) signal of a human originates from water and fat molecules. By utilizing the property chemical shift the signal can be separated, creating water- and fat-only images. From these images it is possible to calculate quantitative fat fraction (FF) images, where the value of each voxel is equal to the percentage of its signal originating from fat. In papers I and II methods for water–fat signal separation are presented and evaluated.The method in paper I utilizes a graph-cut to separate the signal and was designed to perform well even for a low signal-to-noise ratio (SNR). The method was shown to perform as well as previous methods at high SNRs, and better at low SNRs.The method presented in paper II uses convolutional neural networks to perform the signal separation. The method was shown to perform similarly to a previous method using a graph-cut when provided non-undersampled input data. Furthermore, the method was shown to be able to separate the signal using undersampled data. This may allow for accelerated MRI scans in the future.Brown adipose tissue (BAT) is a thermogenic organ with the main purpose of expending chemical energy to prevent the body temperature from falling too low. Its energy expending capability makes it a potential target for treating overweight/obesity and metabolic dysfunctions, such as type 2 diabetes. The most well-established way of estimating the metabolic potential of BAT is through measuring glucose uptake using 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) during cooling. This technique exposes subjects to potentially harmful ionizing radiation, and alternative methods are desired. One alternative method is measuring the BAT FF using MRI.In paper III the BAT FF in 7-year olds was shown to be negatively associated with blood serum levels of the bone-specific protein osteocalcin and, after correction for adiposity, thigh muscle volume. This may have implications for how BAT interacts with both bone and muscle tissue.In paper IV the glucose uptake of BAT during cooling of adult humans was measured using 18F-FDG PET. Additionally, their BAT FF was measured using MRI, and their skin temperature during cooling near a major BAT depot was measured using infrared thermography (IRT). It was found that both the BAT FF and the temperature measured using IRT correlated with the BAT glucose uptake, meaning these measurements could be potential alternatives to 18F-FDG PET in future studies of BAT.
|
|
| 38. |
- Andersson, Lotta E., et al.
(author)
-
Glutamine-elicited secretion of glucagon-like peptide 1 is governed by an activated glutamate dehydrogenase
- 2018
-
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:3, s. 372-384
-
Journal article (peer-reviewed)abstract
- Glucagon-like peptide 1 (GLP-1), secreted from intestinal L cells, glucose dependently stimulates insulin secretion from β-cells. This glucose dependence prevents hypoglycemia, rendering GLP-1 analogs a useful and safe treatment modality in type 2 diabetes. Although the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear. We investigated how GLP-1 secretion is metabolically coupled in L cells (GLUTag) and in vivo inmice using the insulin-secreting cell line INS-1 832/13 as reference. A membrane-permeable glutamate analog (dimethylglutamate [DMG]), acting downstream of electrogenic transporters, elicited similar alterations in metabolism as glutamine in both cell lines. Both DMG and glutamine alone elicited GLP-1 secretion in GLUTag cells and in vivo, whereas activation of glutamate dehydrogenase (GDH) was required to stimulate insulin secretion from INS-1 832/13 cells. Pharmacological inhibition in vivo of GDH blocked secretion of GLP-1 in response to DMG. In conclusion, our results suggest that nonelectrogenic nutrient uptake and metabolism play an important role in L cell stimulus-secretion coupling. Metabolism of glutamine and related analogs by GDH in the L cell may explain why GLP-1 secretion, but not that of insulin, is activated by these secretagogues in vivo.
|
|
| 39. |
- Andersson, Magnus, et al.
(author)
-
A proposed time-resolved X-ray scattering approach to track local and global conformational changes in membrane transport proteins
- 2008
-
In: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 16:1, s. 21-28
-
Journal article (peer-reviewed)abstract
- Time-resolved X-ray scattering has emerged as a powerful technique for studying the rapid structural dynamics of small molecules in solution. Membrane-protein-catalyzed transport processes frequently couple large-scale conformational changes of the transporter with local structural changes perturbing the uptake and release of the transported substrate. Using light-driven halide ion transport catalyzed by halorhodopsin as a model system, we combine molecular dynamics simulations with X-ray scattering calculations to demonstrate how small-molecule time-resolved X-ray scattering can be extended to the study of membrane transport processes. In particular, by introducing strongly scattering atoms to label specific positions within the protein and substrate, the technique of time-resolved wide-angle X-ray scattering can reveal both local and global conformational changes. This approach simultaneously enables the direct visualization of global rearrangements and substrate movement, crucial concepts that underpin the alternating access paradigm for membrane transport proteins.
|
|
| 40. |
- Andersson, Mariam, et al.
(author)
-
Axon morphology is modulated by the local environment and impacts the noninvasive investigation of its structure-function relationship
- 2020
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:52, s. 33649-33659
-
Journal article (peer-reviewed)abstract
- Axonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Noninvasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires three-dimensional (3D) validation. Here, high-resolution, 3D synchrotron X-ray nano-holotomography images of white matter samples from the corpus callosum of a monkey brain reveal that blood vessels, cells, and vacuoles affect axonal diameter and trajectory. Within single axons, we find that the variation in diameter and conduction velocity correlates with the mean diameter, contesting the value of precise diameter determination in larger axons. These complex 3D axon morphologies drive previously reported 2D trends in axon diameter and g-ratio. Furthermore, we find that these morphologies bias the estimates of axon diameter with diffusion magnetic resonance imaging and, ultimately, impact the investigation and formulation of the axon structure-function relationship.
|
|
| 41. |
- Andersson, Marica, et al.
(author)
-
Low Holding Densities Increase Stress Response and Aggression in Zebrafish
- 2022
-
In: Biology. - : MDPI AG. - 2079-7737. ; 11:5
-
Journal article (peer-reviewed)abstract
- Simple Summary Zebrafish are used as experimental animals in labs all around the world. To ensure that the health of zebrafish is maintained at the highest level, it is important to know the optimal housing conditions of the animals, including the housing density. Guidelines for housing densities of zebrafish can then be spread and followed globally, making it possible to compare research data from different facilities. To investigate the optimal housing densities of zebrafish and to better understand how holding density affects zebrafish behaviour and physiology, we evaluated the welfare of zebrafish housed at different densities for nine weeks. We observed that fish housed at the lowest holding density of 1 fish/L stood out from the rest of the experimental fish, showing higher levels of aggression, secreting more of the stress hormone cortisol in the water, and spending more time in the top zone of the tank, possibly reflecting the fact that fish in this density were hiding more behind the floating plants. Our data indicate that zebrafish should not be kept at 1 fish/L, or lower, to ensure good welfare of the animals. With laboratory zebrafish (Danio rerio) being an established and popular research model, there is a need for universal, research-based husbandry guidelines for this species, since guidelines can help promote good welfare through providing appropriate care. Despite the widespread use of zebrafish in research, it remains unclear how holding densities affect their welfare. Previous studies have mainly evaluated the effects of holding densities on a single parameter, such as growth, reproductive output, or social interactions, rather than looking at multiple welfare parameters simultaneously. Here we investigated how chronic (nine weeks) exposure to five different holding densities (1, 4, 8, 12, and 16 fish/L) affected multiple welfare indicators. We found that fish in the 1 fish/L density treatment had higher free water cortisol concentrations per fish, increased vertical distribution, and displayed aggressive behaviour more frequently than fish held at higher densities. On the other hand, density treatments had no effect on anxiety behaviour, whole-brain neurotransmitter levels, egg volume, or the proportion of fertilised eggs. Our results demonstrate that zebrafish can be held at densities between 4 and 16 fish/L without compromising their welfare. However, housing zebrafish in the density of 1 fish/L increased their stress level and aggressive behaviour.
|
|
| 42. |
|
|
| 43. |
- Andersson, Pia, et al.
(author)
-
Marine Acidification : On effects and monitoring of marine acidification in the seas surrounding Sweden
- 2008. - 2008:92
-
Reports (other academic/artistic)abstract
- Surface waters in the world oceans have already experienced a pH reduction of about 0.1 units (OSPAR, 2006.) The trend indicates further decrease of pH and is most probably due to increased uptake of atmospheric CO2 and less buffering capacity of ocean waters. The trend is similar in the waters surrounding Sweden. RESEARCH NEEDS Since there is an alarming absence of information regarding the effects of near-future levels of ocean acidification on Swedish marine taxa, there is a clear research need on: • investigations of the effects of ocean acidification on the early life-history stages of key ecosystem-structuring species, and commercially important species of fish and shellfish • ecosystem-level mesocosm studies of the impacts of ocean acidification on Swedish marine systems • improved regional-scale modelling of acidification mechanisms in Swedish coastal waters • testable ecosystem-scale food-web models to articulate with regional acidification models • improved definition of chemical equilibrium constants between pH, AT and CO2 in low saline waters. ACTIONS TO IMPROVE MONITORING At present, pH and AT are monitored monthly at standard depths at 7 stations in Skagerrak, Kattegat and Baltic Proper within the national monitoring programme. Of these are 2 located in coastal waters (Halland and Småland; Type 5 and 9). We recommend that Sweden work to improve the status of pH and AT to be Core variables instead of Main variables in HELCOM COMBINE “High frequency Sampling” program taking into account the last 15 years negative trends in pH in waters surrounding Sweden as well as in the global oceans. We recommend that besides the standard para-meters monitored in the national monitoring program, pH, AT and DIC should be monitored. For completeness, primary production should also be monitored. Below are three monitoring recommendations, where the first is divided into a lowest level and a recommended level. 1. Lowest level: Within the national monitoring program, at least one station per open sea area and all costal stations measure acidification parameters on a monthly basis in the entire water column at standardized depths. The national and regional monitoring programmes should be upgraded in the Gulf of Bothnia so that pH and AT is monitored at standard depths at least monthly at one station each in the Bothnian Bay and Bothnian Sea. Also 2 coastal stations in the Gulf of Bothnia should be established. In addition, one coastal station should be established within Type 14 in the Baltic Proper. 1. Recommended level: the national monitoring program should have at least one station per open sea area and if the area is characterized by strong gradients or other features, there should be more than one station. Some of the stations in the regional monitoring programmes should be upgraded with acidification parameters, for a better geographical coverage. The acidification parameters should be measured on a monthly basis in the entire water column at standardized depths. 2. We recommend that an investigative monitoring is established by extending the parameters that are needed to firmly improve the chemical stability constants between pH, AT, DIC and pCO2 in low saline waters. This can be done by just extending the sampling program at selected monitoring stations. Sampling should cover a period of 2 to 3 years. 3. We recommend that direct water measurement of pCO2 for monitoring purposes should be assessed after the recommendation above is evaluated and that ongoing research projects on pCO2 measurements using ferryboxes are finalised. RECOGNISED PROBLEM AREAS • There are only few long time series of acidification parameters. The time period of measurements is rather short. • The geographical coverage of measurements is rather limited in the waters surrounding Sweden. • The chemical stability constants between pH, AT, DIC and pCO2 are not optimized in low saline waters. • pH budgets are difficult to calculate. • Models need to be improved in order to display present and future small and large scale scenarios. • Little is known of the biological, ecological and economical effects of the current and near future marine acidification. Further research is required.
|
|
| 44. |
- Andersson, Per-Åke, 1945-
(author)
-
Multi-year maintenance optimisation for paved public roads - segment based modelling and price-directive decomposition
- 2007
-
Doctoral thesis (other academic/artistic)abstract
- I avhandlingen studeras hur kostnadseffektiva underhålls- (uh-)planer för belagd väg kan genereras, på basis av information om aktuellt vägytetillstånd och funktionella modeller för kostnads- och tillståndsförändringar, delvis utvecklade i samarbete med svenska Vägverket (VV). Tilltänkt användning är på strategisk och programnivå, innan mer detaljerad objektinformation finns att tillgå. Till skillnad från hittills använda modeller, så genereras individuella uh-planer för varje vägsegment (en homogen vägsträcka vad gäller aktuellt beläggningstillstånd och beläggningshistorik), i kontinuerliga tillstånds- och åtgärdsrum. Genom användning av Lagrangerelaxerande optimeringsteknik, så kan de speciella nytto/kostnads-kvot-villkor som VV ålägger varje uh-objekt naturligen hanteras med dualpriser för budgetvillkoren. Antalet vägsegment som konkurrerar om budgetmedlen är vanligtvis stort. Data från VV:s Vägdatabank för Värmland har använts, omfattande ca 9000 vägsegment. Genom den stora datamängden har datorprogrammen implementerats för parallellbearbetning. Under avhandlingsarbetet har projektet beviljats tillgång till Monolith PCklustret vid NSC. För att kunna reducera optimeringskörtiderna har modell- och metodutveckling varit nödvändig. Genom att aggregera vägsegmenten till vägklasser har goda startvärden på dualpriserna erhållits. Genom utvecklingen av en speciell restvärdesrutin har den explicit behandlade tidsperioden kunnat reduceras. Vid lösandet av det duala subproblemet har speciell uppmärksamhet ägnats åt de diskretiseringseffekter som uppstår i metoden dynamisk programmering. En typ av tillämpning avser ett delvägnät, exempelvis en väg. Valideringsstudier har genomförts på väg 63 i Värmland – med lovande men inte tillfredsställande resultat (se nedan). En speciell modell för samordnat uh beaktar stordriftsfördelarna vid samtidig åtgärd på en hel vägsträcka. Den andra huvudtypen av studier gäller ett helt nätverk. Flera metodtyper har tillämpats, både för att lösa de relaxerade optimeringsproblemen och för att generera uhplaner som uppfyller budgetvillkoren. För en anständig diskretisering är körtiderna för hela Värmland mindre än 80 CPU-timmar. Genom en a posteriori primal heuristik reduceras kraven på parallellbearbetning till ett litet PC-kluster. Avhandlingen studerar vidare effekterna av omfördelade budgetmedel samt en övergång till en transparent, stokastisk modell – vilka båda visar små avvikelser från basmodellen.Optimeringsresultaten för Värmland indikerar att budgetnivåer på ca 40% av Värmlands verkliga uh-budget är tillräckliga. Dock saknas viktiga kostnadsdrivande faktorer i denna första modellomgång, exempelvis vissa funktionella prestanda (säkerhet), all miljöpåverkande prestanda (buller etc.) och strukturell prestanda (ex.vis bärighet, som enbart modelleras via ett åldersmått). För ökad tilltro till PMS i allmänhet och optimering i synnerhet, bör avvikelserna analyseras ytterligare och leda till förbättringar vad gäller tillståndsmätning, tillståndseffekt- & kostnadsmodellering samt matematisk modellering & implementering.
|
|
| 45. |
- Andersson, Sofia A, et al.
(author)
-
Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.
- 2012
-
In: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 364:1-2, s. 36-45
-
Journal article (peer-reviewed)abstract
- Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis.
|
|
| 46. |
|
|
| 47. |
- Arvanitis, Dimitri, et al.
(author)
-
Influence of ligand states on the relationship between orbital moment and magnetocrystalline anisotropy
- 2007
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 99:17, s. 177207-
-
Journal article (peer-reviewed)abstract
- The spin and orbital moments of Au/Co/Au trilayers grown on a W(110) single crystal substrate have been investigated by means of x-ray magnetic circular dichroism. Our findings suggest that the orbital moment of Co does not obtain a maximum value along the easy axis, in contrast with previous experience. This is attributed to the large spin-orbit interaction within the Au caps. Both second order perturbation theory and first principles calculations show how the magnetocrystalline anisotropy (MCA) is dramatically influenced by this effect, and how this leads to the fact that the orbital moment anisotropy is not proportional to the MCA.
|
|
| 48. |
- Baldwin, Scott A., et al.
(author)
-
Intraclass correlation associated with therapists : estimates and applications in planning psychotherapy research
- 2011
-
In: Cognitive Behaviour Therapy. - : Routledge, Taylor and Francis Group. - 1650-6073 .- 1651-2316. ; 40:1, s. 15-33
-
Journal article (peer-reviewed)abstract
- It is essential that outcome research permit clear conclusions to be drawn about the efficacy of interventions. The common practice of nesting therapists within conditions can pose important methodological challenges that affect interpretation, particularly if the study is not powered to account for the nested design. An obstacle to the optimal design of these studies is the lack of data about the intraclass correlation coefficient (ICC), which measures the statistical dependencies introduced by nesting. To begin the development of a public database of ICC estimates, the authors investigated ICCs for a variety outcomes reported in 20 psychotherapy outcome studies. The magnitude of the 495 ICC estimates varied widely across measures and studies. The authors provide recommendations regarding how to select and aggregate ICC estimates for power calculations and show how researchers can use ICC estimates to choose the number of patients and therapists that will optimize power. Attention to these recommendations will strengthen the validity of inferences drawn from psychotherapy studies that nest therapists within conditions.
|
|
| 49. |
- Bergman, Joakim, 1989-
(author)
-
Studies of the Biology of Intrathecal Treatment in Progressive MS
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- Background: Multiple Sclerosis (MS) is a chronic, inflammatory, autoimmune disease, affecting the central nervous system (CNS). About 85% of afflicted present with a relapsing-remitting form of the disease (RRMS), for which a breakthrough in treatment was made in 2008 with rituximab, an antibody directed towards CD20, a surface antigen on B-cells. These findings also contributed to cementing the importance of the B-cell’s role in MS pathophysiology. However, MS also exist as a progressive phenotype, affecting most MS patients either from onset or after a transition from RRMS, and for progressive MS the same treatment effect of anti-CD20 has not been observed. Still, studies have found follicle-like structures containing B-cells in meninges and subarachnoid space of the cortex in progressive MS brains, supporting the involvement of B-cells. Evidence also support the existence of a chronic, low-grade inflammatory process compartmentalised within the CNS that correlates with the progressive phase of MS, which may present a treatment barrier towards anti-CD20. Peripherally administrated therapeutic antibodies cross the intact blood-brain barrier with low efficiency with only 0.1-0.5% of the plasma concentration occurring in the cerebrospinal fluid (CSF). Intrathecal (IT) administration circumvents the blood-brain barrier, presenting an opportunity to better target the CNS B-cells.Aims: To evaluate the safety and feasibility of intrathecal anti-CD20 therapy with rituximab in progressive MS, its effect on disease progression through clinical parameters, and impact on biomarkers in CSF. Furthermore, this thesis aimed to evaluate the effect on biomarkers representative of cell injury related to insertion of a ventricular catheter for drug administration and to examine the interstitial milieu in the brain through microdialysis (MD).Methods: The thesis is based on the open-label, phase IIb, multicentre clinical trial Intrathecal Treatment Trial in Progressive Multiple Sclerosis (ITT-PMS; EudraCT 2008-002626-11), in which 23 participants received IT treatment with rituximab, and the extended follow-up study, ITT-PMS extension (EudraCT 2012-000721-53). All participants received a ventricular catheter and an Ommaya reservoir for drug administration through a neurosurgical procedure, and 10 participants received a MD catheter in parallel to the ventricular catheter for 10 days. The treatment effect was evaluated by regular clinical evaluations and analyses of CSF. The clinical outcome was evaluated through walking and upper-limb function tests, and by clinical evaluation scales. Levels of selected CSF biomarkers were analysed from the same time-points as the clinical evaluations.Results: After the completion of the extension trial, one clinical parameter (cognitive performance) showed improvement but could most likely be explained by a learning effect. Worsening of walking speed was observed, while the remaining clinical parameters showed no change. Two severe adverse events occurred in the form of low-virulent bacterial meningitis caused by Propionibacterium, but both were treated effectively with antibiotics without residual symptoms. A ‘spike’ was noticed in the level of lumbar CSF neurofilament light (NFL) following surgery but returned to pre-surgery baseline within 6-12 months. No change was observed for any of the other lumbar CSF biomarkers. No meaningful correlation of protein levels was observed when comparing MD samples, ventricular CSF, and lumbar CSF.Conclusions: Intrathecal treatment through intraventricular administration was well tolerated but not without risks. A continued progression was observed in gait impairment. The insertion of the ventricular catheter caused white matter injury, measured through an increase in NFL in lumbar CSF, in direct association with the surgical procedure. No impact was observed on other CSF biomarkers. There was a poor correlation between different CNS compartments regarding protein levels, arguing for caution in drawing conclusions about brain pathophysiology from lumbar CSF samples.
|
|
| 50. |
|
|
