| 1. |
- Holm, Åsa, et al.
(author)
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A linear programming model for optimizing HDR brachytherapy dose distributions with respect to mean dose in the DVH-tail
- 2013
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In: Medical physics (Lancaster). - : American Association of Physicists in Medicine. - 0094-2405. ; 40:8
-
Journal article (peer-reviewed)abstract
- Purpose: Recent research has shown that the optimization model hitherto used in high-dose-rate (HDR) brachytherapy corresponds weakly to the dosimetric indices used to evaluate the quality of a dose distribution. Although alternative models that explicitly include such dosimetric indices have been presented, the inclusion of the dosimetric indices explicitly yields intractable models. The purpose of this paper is to develop a model for optimizing dosimetric indices that is easier to solve than those proposed earlier. less thanbrgreater than less thanbrgreater thanMethods: In this paper, the authors present an alternative approach for optimizing dose distributions for HDR brachytherapy where dosimetric indices are taken into account through surrogates based on the conditional value-at-risk concept. This yields a linear optimization model that is easy to solve, and has the advantage that the constraints are easy to interpret and modify to obtain satisfactory dose distributions. less thanbrgreater than less thanbrgreater thanResults: The authors show by experimental comparisons, carried out retrospectively for a set of prostate cancer patients, that their proposed model corresponds well with constraining dosimetric indices. All modifications of the parameters in the authors model yield the expected result. The dose distributions generated are also comparable to those generated by the standard model with respect to the dosimetric indices that are used for evaluating quality. less thanbrgreater than less thanbrgreater thanConclusions: The authors new model is a viable surrogate to optimizing dosimetric indices and quickly and easily yields high quality dose distributions.
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| 2. |
- Holm, Åsa
(author)
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Dose Plan Optimization in HDR Brachytherapy using Penalties : Properties and Extensions
- 2011
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Licentiate thesis (other academic/artistic)abstract
- High dose-rate (HDR) brachytherapy is a specific type of radiotherapy used to treat tumours of for example the cervix, prostate, and breasts. In HDR brachytherapy applicators are implanted into or close to the tumour volume. A radioactive source is moved through these applicators and stops at certain positions, known as dwell points. For each patient an anatomy-based dose plan is created that decides for example where to place the applicators, which dwell points to use, and for how long. The aim when creating a dose plan is to deliver an as high dose as possible to the tumour while simultaneously keeping the dose to the surrounding healthy organs as low as possible.In order to improve the quality of dose plans mathematical optimization methods are today used in clinical practice. Usually one solves a linear penalty model that minimizes a weighted deviation from dose intervals provided by a physician. In this thesis we study certain properties and alterations of this model.One interesting property of the model that we study is the distribution of the basic variables. We show that due to the distribution of these variables only a limited number of dwell positions can be used. Since relatively few dwell positions are used some of the corresponding dwell times have to be long in order for the desired overall dose level to be reached. These long dwell times have been observed in clinical practice and are considered to be a problem.Another property that we study is the correlation between the objective value of the linear penalty model and dose-volume parameters used for evaluation of dose plans. We show that the correlation is weak, which implies that optimizing the linear penalty model does not give a solution to the correct problem.Some alternative models are also considered. One that includes into the optimization the decision of where to place the applicators, when HDR brachytherapy is applied for prostate cancer, and one that reduces the long dwell times by using piecewise linear penalties. The solutions to both models show significant improvements.
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| 3. |
- Holm, Åsa, et al.
(author)
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Heuristics for Integrated Optimization of Catheter Positioning and Dwell Time Distribution in Prostate HDR Brachytherapy
- 2016
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In: Annals of Operations Research. - : Springer. - 0254-5330 .- 1572-9338. ; 236:2, s. 319-339
-
Journal article (peer-reviewed)abstract
- High dose-rate (HDR) brachytherapy is a kind of radiotherapy used to treat, among others, prostate cancer. When applied to prostate cancer a radioactive source is moved through catheters implanted into the prostate. For each patient a treatment plan is constructed that decide for example catheter placement and dwell time distribution, that is where to stop the radioactive source and for how long.Mathematical optimization methods has been used to find quality plans with respect to dwell time distribution, however few optimization approaches regarding catheter placement have been studied. In this article we present an integrated optimization model that optimize catheter placement and dwell time distribution simultaneously. Our results show that integrating the two decisions yields greatly improved plans, from 15% to 94% improvement.Since the presented model is computationally demanding to solve we also present three heuristics: tabu search, variable neighbourhood search and genetic algorithm. Of these variable neighbourhood search is clearly the best, outperforming a state-of-the-art optimization software (CPLEX) and the two other heuristics.
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| 4. |
- Holm, Åsa, et al.
(author)
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Impact of Using Linear Optimization Models in Dose Planning for HDR Brachytherapy
- 2012
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In: Medical physics (Lancaster). - : American Association of Physicists in Medicine. - 0094-2405. ; 39:2, s. 1021-1028
-
Journal article (peer-reviewed)abstract
- Purpose: Dose plans generated with optimization models hitherto used in HDR brachytherapy have shown a tendency to yield longer dwell times than manually optimized plans. Concern has been raised for the corresponding undesired hot spots and various methods to mitigate these have been developed. The hypotheses of this work are a) that one cause for the long dwell times is the use of objective functions comprising simple linear penalties and b) that alternative penalties, being piecewise linear, would lead to reduced length of individual dwell times.Methods: The characteristics of the linear penalties and the piecewise linear penalties are analysed mathematically. Experimental comparisons between the two types of penalties are carried out retrospectively for a set of prostate cancer patients.Results: While most dose-volume parameters do not differ significantly between the two types of penalties significant changes can be seen in the dwell times. On the average, total dwell times were reduced by 4.2%, with a reduction of maximum dwell times by 30%, using the alternative penalties.Conclusion: The use of linear penalties in optimization models for HDR brachytherapy is one cause for undesired longer dwell times appearing in mathematically optimized plans. By introducing alternative penalties significant reduction in dwell times can be achieved for HDR brachytherapy dose plans. Although various constraints as to reduce the long dwell times have been developed our finding is of fundamental interest in showing the shape of the objective function to be one reason for their appearance.
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| 5. |
- Holm, Åsa
(author)
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Mathematical Optimization of HDR Brachytherapy
- 2013
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Doctoral thesis (other academic/artistic)abstract
- One out of eight deaths throughout the world is due to cancer. Developing new treatments and improving existing treatments is hence of major importance. In this thesis we have studied how mathematical optimization can be used to improve an existing treatment method: high-dose-rate (HDR) brachytherapy.HDR brachytherapy is a radiation modality used to treat tumours of for example the cervix, prostate, breasts, and skin. In HDR brachytherapy catheters are implanted into or close to the tumour volume. A radioactive source is moved through the catheters, and by adjusting where the catheters are placed, called catheter positioning, and how the source is moved through the catheters, called the dwelling time pattern, the dose distribution can be controlled.By constructing an individualized catheter positioning and dwelling time pattern, called dose plan, based on each patient's anatomy, it is possible to improve the treatment result. Mathematical optimization has during the last decade been used to aid in creating individualized dose plans. The dominating optimization model for this purpose is a linear penalty model. This model only considers the dwelling time pattern within already implanted catheters, and minimizes a weighted deviation from dose intervals prescribed by a physician.In this thesis we show that the distribution of the basic variables in the linear penalty model implies that only dwelling time patterns that have certain characteristics can be optimal. These characteristics cause troublesome inhomogeneities in the plans, and although various measures for mitigating these are already available, it is of fundamental interest to understand their cause.We have also shown that the relationship between the objective function of the linear penalty model and the measures commonly used for evaluating the quality of the dose distribution is weak. This implies that even if the model is solved to optimality there is no guarantee that the generated plan is optimal with respect to clinically relevant objectives, or even near-optimal. We have therefore constructed a new model for optimizing the dwelling time pattern. This model approximates the quality measures by the concept conditional value-at-risk, and we show that the relationship between our new model and the quality measures is strong. Furthermore, the new model generates dwelling time patterns that yield high-quality dose distributions.Combining optimization of the dwelling time pattern with optimization of the catheter positioning yields a problem for which it is rarely possible to find a proven optimal solution within a reasonable time frame. We have therefore developed a variable neighbourhood search heuristic that outperforms a state-of-the-art optimization software (CPLEX). We have also developed a tailored branch-and-bound algorithm that is better at improving the dual bound than a general branch-and-bound algorithm. This is a step towards the development of a method that can find proven optimal solutions to the combined problem within a reasonable time frame.
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| 6. |
- Holm, Åsa, et al.
(author)
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On the Correlation Between DVH Parameters and Linear Penalties in Optimization of HDR Prostate Brachytherapy Dose Plans
-
Other publication (other academic/artistic)abstract
- When optimizing dwell times for HDR brachytherapy it is common to use a model comprising an objective of linear penalties. However whether a planis considered good or not depends on other measures such as DVH-based parameters. We show through experiments that the correlation between the value of the objective function and the values of DVH-based parameters, such as D90, is weak in some cases. It seems that the objective function can only classify solutions into better or worse, however it can not distinguish the best with respect to DVH-based parameters.
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| 7. |
- Holm, Åsa, et al.
(author)
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Study of the Relationship Between Dosimetric Indices and Linear Penalties in Dose Distribution Optimization for HDR Prostate Brachytherapy
- 2013
-
Other publication (other academic/artistic)abstract
- Purpose: Most clinical software for optimizing dwelling time patterns is based on a linear penalty model. The quality of a dose distribution generated by the dwelling time pattern is, however, evaluated through a number of dosimetric indices. The purpose of this article is to investigate the relationship between the linear penalty model and the dosimetric indices.Method and Materials: Data sets from three patients, previously treated for prostate cancer with HDR brachytherapy as a boost to external beam therapy, were used for this study, and for each of them 300 random dwelling time patterns were generated. The relationship between the linear penalty model and the dosimetric indices were studied both by the Pearson’s product moment correlation coefficient between the objective function value of the linear penalty model and the values of the dosimetric indices, and by scatter-grams.Results: For one of the three patients we found a clear connection between the linear penalty model and the values of the dosimetric indices, but not for the other two. For the two patients without a clear connection there where some dosimetric indices that actually improved with deteriorating objective function value.Conclusion: The dwelling time pattern found by using the linear penalty model does not correspond to the optimal dose distribution with respect to dosimetric indices.
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| 8. |
- Strand, Åsa, et al.
(author)
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Impact of an icy winter on the Pacific oyster (Crassostrea gigas Thunberg, 1793) populations in Scandinavia
- 2012
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In: Aquatic Invasions. - : Regional Euro-Asian Biological Invasions Centre Oy (REABIC). - 1798-6540 .- 1818-5487. ; 7:3, s. 433-440
-
Journal article (peer-reviewed)abstract
- The Pacific oyster (Crassostrea gigas) is an invasive species that has dispersed into Scandinavia during the last few decades. The objective of this study was to evaluate the effects of extreme winter conditions on the mortality of the Pacific oyster in Scandinavia. The study was done by compiling mortality data from independent surveys in Denmark, Sweden and Norway. Winter mortality of the oysters increased with latitude, which can be explained by the colder climate experienced at higher latitudes. Mortality was also found to be affected by site specific conditions such as water depth at the sampling sites of oyster populations. Despite the severe winter conditions of 2009/2010 causing high mortality, the Pacific oyster still exists in large numbers in Scandinavia. The present investigation indicates that extreme winter conditions may result in a temporary reduction of the density of the Pacific oyster, but that the species can be expected to continue its invasion of Scandinavian coastal areas.
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| 9. |
- Adler, Mats, et al.
(author)
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Diagnosdiskussion
- 2016
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In: Tidskriften för Svensk Psykiatri. - 1653-8579. ; 2016:1, s. 77-78
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Journal article (other academic/artistic)abstract
- Senaste halvåret har en arbetsgrupp på Svenska Psykiatriska Föreningens uppdrag arbetat med problem som finns runt psykiatriska diagnoser. En viktig del av arbetet har varit att ta fram ett diskussionsunderlag främst riktat till dem som i sitt arbete sätter psykiatriska diagnoser. Detta underlag syftar till att problematisera, inte till att polemisera. Självklart har vi i gruppen uppfattningar, men vi har inte alltid samma uppfattningar inom detta område. En sak är vi dock helt överens om – psykiatrisk diagnostik är svårt! samt att det idag finns uppenbara problem.
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| 10. |
- Adler, Mats, et al.
(author)
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Psykiatrisk diagnostik är svårt.
- 2015
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In: Tidskriften för Svensk Psykiatri. - 1653-8579. ; 2015:4, s. 36-37
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Journal article (other academic/artistic)
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| 11. |
- Ahlgren, Lina, et al.
(author)
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Nätverk - en förutsättning för pedagogisk utveckling?
- 2020
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In: Nordic Journal of Information Literacy in Higher Education. - : Universtity of Bergen Library. - 1890-5900. ; 12:1, s. 41-49
-
Journal article (peer-reviewed)abstract
- The importance of networking is often emphasized in higher education teaching and learning. In this article we discuss significant networks and their impact on pedagogical development. We also share our experience of working in different kinds of networks. We focus on a Nordic project with the aim to develop digital learning objects in co-creation between librarians, students and teachers.
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| 12. |
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| 13. |
- Arking, D. E., et al.
(author)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
-
Journal article (peer-reviewed)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Barnevik Olsson, Martina, et al.
(author)
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Children with borderline intellectual functioning and autism spectrum disorder : developmental trajectories from 4 to 11 years of age
- 2017
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In: Neuropsychiatric Disease and Treatment. - 1176-6328 .- 1178-2021. ; 13, s. 2519-2526
-
Journal article (peer-reviewed)abstract
- Background: Studies on autism have tended to focus either on those with intellectual disability (ie, those with intellectual quotient [IQ] under 70) or on the group that is referred to as high-functioning, that is, those with borderline, average or above average IQ. The literature on cognition and daily functioning in autism spectrum disorder combined specifically with borderline intellectual functioning (IQ 70-84) is limited. Methods: From a representative group of 208 preschool children diagnosed with autism spectrum disorder, those 50 children in the group with borderline intellectual functioning at ages 4.5-6.5 years were targeted for follow-up at a median age of 10 years. A new cognitive test was carried out in 30 children. Parents were interviewed with a semi-structured interview together with the Vineland Adaptive Behavior Scales (n=41) and the Autism-Tics, attention-deficit/hyperactivity disorder (AD/HD) and other comorbidities inventory (A-TAC) (n=36). Results: Most children of interviewed parents presented problems within several developmental areas. According to A-TAC and the clinical interview, there were high rates of attention deficits and difficulties with regulating activity level and impulsivity. Vineland Adaptive Behavior Scales composite scores showed that at school age, a majority of the children had declined since the previous assessment at ages between 4.5 and 6.5 years. Almost half the tested group had shifted in their IQ level, to below 70 or above 84. Conclusion: None of the children assessed was without developmental/neuropsychiatric problems at school-age follow-up. The results support the need for comprehensive follow-up of educational, medical and developmental/neuropsychiatric needs, including a retesting of cognitive functions. There is also a need for continuing parent/family follow-up and support.
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| 18. |
- Barnevik Olsson, Martina, et al.
(author)
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Children with borderline intellectual functioning and autism spectrum disorder: developmental trajectories from 4 to 11 years of age
- 2017
-
In: Neuropsychiatric Disease and Treatment. - : Informa UK Limited. - 1178-2021. ; 13, s. 2519-2526
-
Journal article (peer-reviewed)abstract
- Background: Studies on autism have tended to focus either on those with intellectual disability (ie, those with intellectual quotient [IQ] under 70) or on the group that is referred to as "high-functioning", that is, those with borderline, average or above average IQ. The literature on cognition and daily functioning in autism spectrum disorder combined specifically with borderline intellectual functioning (IQ 70-84) is limited. Methods: From a representative group of 208 preschool children diagnosed with autism spectrum disorder, those 50 children in the group with borderline intellectual functioning at ages 4.5-6.5 years were targeted for follow-up at a median age of 10 years. A new cognitive test was carried out in 30 children. Parents were interviewed with a semi-structured interview together with the Vineland Adaptive Behavior Scales (n=41) and the Autism-Tics, attention-deficit/hyperactivity disorder (AD/HD) and other comorbidities inventory (A-TAC) (n=36). Results: Most children of interviewed parents presented problems within several developmental areas. According to A-TAC and the clinical interview, there were high rates of attention deficits and difficulties with regulating activity level and impulsivity. Vineland Adaptive Behavior Scales composite scores showed that at school age, a majority of the children had declined since the previous assessment at ages between 4.5 and 6.5 years. Almost half the tested group had shifted in their IQ level, to below 70 or above 84. Conclusion: None of the children assessed was without developmental/neuropsychiatric problems at school-age follow-up. The results support the need for comprehensive follow-up of educational, medical and developmental/neuropsychiatric needs, including a retesting of cognitive functions. There is also a need for continuing parent/family follow-up and support.
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| 19. |
- Bång, Åsa, et al.
(author)
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Control of plant species diversity in riparian corridors : Konferens OIKOS 2002
- 2002
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Conference paper (other academic/artistic)abstract
- previous study has shown that plant communities differ floristically between impoundments but remain similar within impoundments in a regulated river. The same pattern did not occur among plant species in a free-flowing river which instead showed a continuous change in species composition from the headwaters to the coast. This strongly suggests that the dispersal of plants is obstructed when dams are built on rivers. The present project will specifically study whether dams also affect the genetic diversity among and between populations of plant species. Filipendula ulmaria will be used as a first test species. A second question is whether tributaries have any impact on the distribution of genetic diversity of plant species within impoundments. A third question deals with the impact of seed and pollen dispersal on the genetic diversity among and between plant species populations. The project combines field sampling, field experiments and laboratory methods such as isoenzymes, microsatellites and other DNA-methods.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Bång, Åsa, et al.
(author)
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The potential role of tributaries as seed sources to an impoundment in northern Sweden : a field experiment with seed mimics
- 2007
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In: Rivers Research and Applications. - : Wiley. - 1535-1459 .- 1535-1467. ; 23:10, s. 1049-1057
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Journal article (peer-reviewed)abstract
- Fragmentation and flow regulation of rivers by large dams are known to obstruct the longitudinal dispersal of waterborne plant propagules between impoundments, and to affect plant community composition. However, even several decades after a dam has been built, impoundments may still have a relatively species-rich riparian flora. We hypothesized that free-flowing tributaries act as the major gene pools for such impoundments, thus alleviating the fragmenting effect large dams have on the main channel. The importance of tributaries as seed sources was tested by releasing wooden seed mimics in three different-sized (0.22-6.93 m3 s-1) tributaries of an impoundment in the Ume River in northern Sweden. In each tributary seed mimics were released, during the spring flood peak, from three points approximately 1, 2 and 3 km upstream the outlet in the impoundment. The importance of a tributary as a seed source increased with tributary size. Of the 9000 released seed mimics 1.5 % reached the impoundment; 1.2 % of the 9000 originated from the largest tributary and 0.3 % from the middle-sized one. The smallest tributary retained all its mimics.
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| 25. |
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| 26. |
- Bång, Åsa, et al.
(author)
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What is the role of tributaries as seed sources for a run-of-river impoundment: a field experiment : Konferens SISORL 2004
- 2004
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Conference paper (other academic/artistic)abstract
- The reservoirs in impounded rivers are blocked by dams, implying that plant seeds, especially waterborne ones, have trouble dispersing between reservoirs. We examined whether the tributaries have an important role in the dispersal of seeds to a specific reservoir. We did this by releasing small, coloured wooden cubes in three tributaries of the Stensele reservoir in northern Sweden, one small, one middle-sized and one large-sized. This work was carried out in spring during major flood. At the day of cube release, we counted the number of cubes that dispersed from the tributaries out into the reservoir. In summer, we collected the cubes that had stranded on the banks of the tributaries to learn how far they had spread within each stream. Our examinations showed that a big stream disperses most seeds the longest distance. The smaller the stream, the shorter the distance the seeds were spread, and the fewer the seeds that reached the reservoir. We concluded that large tributaries have an important role in dispersing plants to reservoirs of impounded rivers.
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| 27. |
- Claesson, Anna-Lena, et al.
(author)
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Two weeks of overfeeding with candy, but not peanuts, increases insulin levels and body weight
- 2009
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In: SCANDINAVIAN JOURNAL OF CLINICAL and LABORATORY INVESTIGATION. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 69:5, s. 598-605
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Journal article (peer-reviewed)abstract
- Objective: To study the effects of snacking based on fast acting carbohydrates (candy) or fat and protein (peanuts) in a prospective randomized, parallel intervention study. Methods: Basal metabolic rate (BMR) and cardiovascular risk factors were measured before and after hyper-alimentation by addition of 20 kcal/kg (84 kJ/kg) body weight of either candy or roasted peanuts, to the regular caloric intake, for two weeks in healthy subjects. Eleven men and 14 women completed the randomized study. Results: Energy-intake increased similarly in the groups (candy: +46.1 +/- 35%, peanuts: +46.8 +/- 28%, p = 0.96). Body-weight (candy: from 67.3 +/- 7.6 kg to 68.1 +/- 7.3 kg, p = 0.01, nuts: from 68.7 +/- 6.1 kg to 69.0 +/- 5.7 kg, p = 0.3) and waist circumference increased significantly only in the candy group. At the end of the study LDL cholesterol (candy: 2.6 +/- 0.4 mmol/L, peanuts: 2.1 +/- 0.4 mmol/L, p = 0.005) and ApoB/ApoA-1-ratio (candy: 0.68 +/- 0.16, peanuts: 0.53 +/- 0.11, p = 0.01) were higher in the candy group than in the peanut group. On the other hand, BMR increased only in the peanut group (candy: from 6.657 +/- 1.1 MJ/24 h to 6.762 +/- 1.1 MJ/24 h, p - 0.3, nuts: from 6.896 +/- 0.98 MJ/24 h to 7.256 +/- 1.1 MJ/24 h, p = 0.02). Conclusion: Two weeks of snacking based on peanuts does not cause the same negative metabolic effects as an isocaloric diet in which the snacking is based on short acting carbohydrates in the form of candy in non-obese healthy subjects.
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| 28. |
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| 29. |
- Claesson, Åsa, et al.
(author)
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Novel design for diode-pumped miniature lasers using microstructured silicon carriers
- 2000
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In: Advanced Solid State Lasers. - : Optica Publishing Group.
-
Conference paper (peer-reviewed)abstract
- A new design concept for compact diode-pumped solid-state lasers is presented. The design is based on a microstructured silicon carrier with etched v-grooves. This silicon microbench provides efficient thermal management at 10W pumping level, as well as compact integration and alignment of all active and passive optical components of compact diode-pumped solid-state lasers. In initial experiments, a Nd:YAG laser built on the microbench delivered a continuous-wave output of 3W.
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| 30. |
- Davis, Monica M., et al.
(author)
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Wild-Type Drosophila melanogaster as a Model Host to Analyze Nitrogen Source Dependent Virulence of Candida albicans
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11, s. e27434-
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Journal article (peer-reviewed)abstract
- The fungal pathogen Candida albicans is a common cause of opportunistic infections in humans. We report that wild-type Drosophila melanogaster (OrR) flies are susceptible to virulent C. albicans infections and have established experimental conditions that enable OrR flies to serve as model hosts for studying C. albicans virulence. After injection into the thorax, wild-type C. albicans cells disseminate and invade tissues throughout the fly, leading to lethality. Similar to results obtained monitoring systemic infections in mice, well-characterized cph1Δ efg1Δ and csh3Δ fungal mutants exhibit attenuated virulence in flies. Using the OrR fly host model, we assessed the virulence of C. albicans strains individually lacking functional components of the SPS sensing pathway. In response to extracellular amino acids, the plasma membrane localized SPS-sensor (Ssy1, Ptr3, and Ssy5) activates two transcription factors (Stp1 and Stp2) to differentially control two distinct modes of nitrogen acquisition (host protein catabolism and amino acid uptake, respectively). Our results indicate that a functional SPS-sensor and Stp1 controlled genes required for host protein catabolism and utilization, including the major secreted aspartyl protease SAP2, are required to establish virulent infections. By contrast, Stp2, which activates genes required for amino acid uptake, is dispensable for virulence. These results indicate that nutrient availability within infected hosts directly influences C. albicans virulence.
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| 31. |
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| 32. |
- Do, Ron, et al.
(author)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Journal article (peer-reviewed)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 33. |
- Dolmer, Per, et al.
(author)
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The invasive Pacific oyster, Crassostrea gigas, in Scandinavian coastal waters: A risk assessment on the impact in different habitats and climate conditions
- 2014
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In: Fisken og havet. - 0071-5638 .- 1894-5031. ; :2
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Journal article (other academic/artistic)abstract
- A massive invasion of the Pacific oyster, Crassostrea gigas, has occurred in Scandinavia during the last decade. The introduction and dispersal was described through collaboration between scientists from Sweden, Denmark and Norway. This work has been followed up by national activities that clearly visualized the need for a continued collaboration between scientists in the Scandinavian countries, as the bio-invasion is a cross-border issue and management actions then have to be synchronized, and based on a “state of the art” knowledge of the Scandinavian bio-invasion of the species. The risk assessment presented in this report is based on available scientific literature, expert judgments and data collected during a Nordic collaboration project on Pacific oysters in 2011 – 2013.
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| 34. |
- Ecke, Frauke, et al.
(author)
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Sublethal Lead Exposure Alters Movement Behavior in Free-Ranging Golden Eagles
- 2017
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:10, s. 5729-5736
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Journal article (peer-reviewed)abstract
- Lead poisoning of animals due to ingestion of fragments from lead-based ammunition in carcasses and offal of shot wildlife is acknowledged globally and raises great concerns about potential behavioral effects leading to increased mortality risks. Lead levels in blood were correlated with progress of the moose hunting season. Based on analyses of tracking data, we found that even sublethal lead concentrations in blood (25 ppb, wet weight), can likely negatively affect movement behavior (flight height and movement rate) of free ranging scavenging Golden Eagles (Aquila chrysaetos). Lead levels in liver of recovered post-mortem analyzed eagles suggested that sublethal exposure increases the risk of mortality in eagles. Such adverse effects on animals are probably common worldwide and across species, where game hunting with lead-based ammunition is widespread. Our study highlights lead exposure as a considerably more serious threat to wildlife conservation than previously realized and suggests implementation of bans of lead ammunition for hunting.
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| 35. |
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| 36. |
- Fernell, Elisabeth, 1948, et al.
(author)
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Developmental profiles in preschool children with autism spectrum disorders referred for intervention.
- 2010
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In: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222 .- 1873-3379. ; 31:3, s. 790-799
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Journal article (peer-reviewed)abstract
- The aim was to characterize the panorama of developmental disorders in 208 preschool children with a clinical diagnosis of autism spectrum disorder (ASD), referred to a specialized centre, the Autism Centre for Young Children (ACYC), for intervention. At the centre, a research team examined all children according to structured protocols and interviews. All available test data from their assessments prior to referral were scrutinized. The boy:girl ratio was 5.5:1. In 22% of the total group a period of regression, including speech and language, had occurred. Epilepsy had been diagnosed in 6% of the children. In 38% of the children there was a definite or highly suspected learning disability/mental retardation according to cognitive test results. About the same proportion had a developmental delay that at the time of assessment could not be definitely classified and in 23% there were clear indications of a normal intellectual function. About 40% of the group exhibited hyperactivity. Differences in expressive vocabulary and adaptive functioning were strongly related to cognitive level. About 20% of the group had AD as the dominating developmental disorder, i.e., they represented a clinical picture of "classic" autism. The majority in this group also had learning disability. Another 20%, had ASD combined with a normal intellectual level, some of these conformed to the clinical picture of Asperger syndrome. In a relatively large group (more than half) learning disability or a general developmental delay was as evident as the ASD. In a smaller group (8%) ASD criteria were questionably met. In this group attention deficits in connection with speech and language problems were prominent. The highly individual developmental profiles seen in children with ASDs have to be taken into account when planning intervention and follow-up. The children's medical characteristics also vary considerably and will be detailed in a further report.
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| 37. |
- Fernell, Elisabeth, 1948, et al.
(author)
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Early intervention in 208 Swedish preschoolers with autism spectrum disorder. A prospective naturalistic study.
- 2011
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In: Research in Developmental Disabilities. - : Elsevier BV. - 1873-3379 .- 0891-4222. ; 32:6, s. 2092-2101
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Journal article (peer-reviewed)abstract
- Early intervention has been reported to improve outcome in children with autism spectrum disorders (ASDs). Several studies in the field have been randomized controlled trials (RCTs). The aim of this study was to assess ASD outcome in a large naturalistic study. Two hundred and eight children, aged 20-54 months, with a clinical diagnosis of ASD were given intervention and monitored prospectively in a naturalistic fashion over a period of 2 years. The toddlers were considered representative of all but the most severely multiple disabled preschool children with ASD in Stockholm county. They fell into three cognitive subgroups: one with learning disability, one with developmental delay, and one with normal intellectual functioning. Data on intervention type and intensity were gathered prospectively in a systematic fashion. Intervention was classified into intensive applied behaviour analysis (ABA) and non-intensive, targeted interventions, also based on ABA principles. Children were comprehensively assessed by a research team before the onset of intervention, and then, again, 2 years later. Change in Vineland adaptive behaviour scales composite scores from intake (T1) to leaving the study (T2) was set as the primary outcome variable. The research team remained blind to the type and intensity of interventions provided. One hundred and ninety-eight (95%) of the original samples stayed in the study throughout the whole 2-year period and 192 children had a complete Vineland composite score results both at T1 and T2. Vineland composite scores increased over the 2-year period. This increase was accounted for by the subgroup with normal cognitive functioning. There was no significant difference between the intensive and non-intensive groups. Individual variation was considerable, but no child in the study was "problem-free" at follow-up. Our data do not support that children with ASD generally benefit more from the most intensive ABA intervention programs than from less intensive interventions or targeted interventions based on ABA.
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| 38. |
- Holm, Anders, 1963-, et al.
(author)
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Ansvarstema : Särskilt om ansvarsmiljöansvar vid frivilligas och ideellas deltagande i räddningsinsatser i glesbygden
- 2023
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In: Framtidens Skadeplats 2023. - 9789180751261 - 9789180751278
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Conference paper (peer-reviewed)abstract
- Ansvarstema: Särskilt om arbetsmiljöansvar vid frivilligas och ideellas deltagande i räddningsinsatser i glesbygden Anta att en räddningsledare finner att en person, vilken som helst, eller att en civil insatsperson, CIP, påbörjat en räddningsinsats i väntan på att räddningstjänsten ska anlända. Anta vidare att räddningsledaren i denna situation uppmanar personen eller CIPen att fortsätta den påbörjade insatsen.Den kort redogjorda situationen ovan är en faktiskt existerande situation runt om i landet, och öppnar upp för flera olika rättsligt relevanta frågor i samband med en räddningsinsats. En av dessa frågor avser vem som har arbetsmiljöansvaret i den uppkomna situationen.I den föreliggande studien fokuseras på ansvarsbegreppet som sådant, på de rättsliga reglerna om arbetsmiljöansvar och på de rättsliga förutsättningarna för arbetsmiljöansvar i de nya samverkansformer för räddningsinsatser, som inkluderar frivilliga och ideella aktörers deltagande. Fokus i studien är i den senare delen riktat mot vem som ansvarar för vilken del av arbetsmiljöansvaret, gentemot vem. Därvid diskuteras de påföljder som kan aktualiseras. Skadestånd, som redan har studerats i Några ansvarsfrågor avseende aktörer, i synnerhet frivilliga, som deltar i räddningsinsatser, utgör därvid en påföljd, men är det en påföljd som är relevant i arbetsmiljösammanhang?När frivilliga och ideella aktörer agerar i en räddningsinsats, innebär det en brytning mot både tidigare organisering av räddningsinsatser och tankar om organiseringen av räddningsinsatser. De nya samverkansformerna avseende räddningsinsatser utmanar rådande reglering. Detta gäller inte minst regleringen av ansvarsfrågor av vitt skilda slag. En fråga som därvid pockar på uppmärksamhet är, i vilken mån det förekommer rättsliga regleringar som i allt för hög grad begränsar möjligheterna till att utveckla de framväxande frivillighetsinitiativen.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Holm, Åsa, 1984-
(author)
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A Tailored Branch-and-Bound Method for Optimizing the Dwelling Time Pattern and Catheter Positioning in HDR Brachytherapy
- 2013
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Reports (other academic/artistic)abstract
- High dose-rate (HDR) brachytherapy is one type of treatment for prostate cancer, in which a radioactive source is moved through catheters implanted into the prostate. For each patient, a unique treatment plan is constructed. This plan determines for example the catheter positioning and the dwelling time pattern, that is, where and for how long the source should stop.Mathematical optimization methods are frequently used to find high-quality dwelling time patterns. However, choosing the catheter positioning is usually done without any aid of mathematical optimization methods. Researchers have recently suggested some optimization models for catheter positioning, and also heuristics for solving them. However, there are no available methods for finding the optimal solution of these models within a clinically acceptable time frame.In this paper we present the foundation for a branch-and-bound method that has been tailored to the catheter positioning problem. Tests show that this tailored branch-and-bound method has some promising features, for example that the dual bound is improved faster than when using a standard branch-and-bound method. But the tests also show that further research is required to develop it into a method that can find the optimal solution fast enough.
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| 45. |
- Holm, Åsa
(author)
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Communicating references in geographically separated collaborative work : an exploratory study
- 2003
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Doctoral thesis (other academic/artistic)abstract
- This thesis is about collaboration between geographically separated small enterprises and how they manage their collaborative efforts. The issue has been explored by studying how the collaborating colleagues handle references during telephone conversations. I have studied settings with very simple means for making references and for separated collaboration, where only telephone, computers with e-mail, faxes and ordinary mail are available for interaction. The reason for studying this simple setting is that these means are still quite commonly utilized among small businesses today. The character of the dissertation is quite empirical. How work is accomplished in practice is of primary interest. It is influenced by ethnomethodological studies about work, video analysis and conversation analysis, even though I don't wish to position it as either a thorough ethnography or a linguistic analysis. The empirical material consists of both interviews and observations. The interviews can be seen as a background for interpreting the collaborative situation between the companies and their partners. They also provide a picture about how those working in those settings experience their collaborative situation. Observations of work in action were made after the interviews and recorded on video. These interviews have been valuable when interpreting the observations and analyzing the videos. The interviews reveal that knowledge about your collaborators, their routines and communication is vital for the success of collaboration. Therefore, communication was studied more closely by using the records of work on video for how references were handled in collaborative sessions. Analysis of the videos told the same story as the interviews: knowledge about collaborators, their routines and their "world" were vital for collaboration in the geographically separated setting. References were made to what can be said to be old knowledge developed through previous common experiences and very little new references were made. Both the interviews and the analysis of the video clips also showed the importance of really sharing the material that was the object of the collaboration as soon as something needed to be discussed. The material was supposed to constitute similar worlds to refer to and to act upon, a substitute for the world they didn't share in reality. Through previous development of a common picture of this material and its content it was possible for the collaborators to talk about it and refer to it. At times when this common picture of the material and the environment was not established problems failed to be solved on distance and personal meetings were arranged. Personal meetings were also arranged when a task was new and undefined or if there was some kind of chaos. The persons in the videos also used more means to express themselves and to clarify their references than were mediated through technology. They also had to create their own private environments to be able to orient themselves to the references and explanations of their collaborators. Thus sharing an environment is necessary in order to be able to collaborate. This shared environment can, at times of geographically separated collaboration, be replaced by a shared picture of the environment, something that can be developed by previous shared experiences. New tasks, new environments or other undefined factors were not adequately established and defined for the collaborators to deal with by phone. It would be interesting to study how references were handled in settings with more advanced technology, allowing collaborators to share environment. There are already technologies that are developed for this purpose and studies about those technologies have been made. Unfortunately, most studies have been more interested in evaluating the technology than to study how collaborators handle references.
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| 46. |
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| 47. |
- Holm, Åsa, 1969-
(author)
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Leishmania donovani lipophosphoglycan : effects on actin and phagosomal maturation
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Leishmania donovani promastigotes survive intracellularly in macrophages by inhibiting phagosomal maturation. This ability is conferred by surface lipophosphoglycan (LPG), which is transferred to the host-cell plasma and phagosomal membranes during phagocytosis. LPG modulates the biophysical properties of membranes and has several effects on the host cell, including inhibition of protein kinase C alpha (PKCα)-mediated signaling. Our studies were focused on molecular mechanisms operating in the establishment of L. donovani infection, especially effects on host-cell F-actin.We found that L. donovani promastigotes induced accumulation of periphagosomal F-actin, an effect directly dependent on LPG. The F-actin accumulation correlated to inhibition of phagosomal maturation. Cortical F-actin was increased as well. Macrophages overexpressing dominant-negative (DN) PKCα also displayed elevated cortical F-actin, decreased phagocytic capacity, elevated periphagosomal F-actin, and defective phagosomal maturation, effects similar to those seen when exposing the cells to LPG. LPG colocalized with lipid rafts in the host-cell membrane, and lipid rafts were necessary both for translocation of activated PKCα to the membrane, and for the effects of LPG on host cell actin dynamics and phagosomal maturation. Introduction of constitutively active Rac1 and Cdc42 into the host macrophage mimicked the effects of LPG on actin dynamics and phagosomal maturation while DN Rac1 and Cdc42 abrogated LPG's effects on actin.Taken together, our results show that LPG partitions into lipid rafts in macrophages and induces an accumulation of periphagosomal F-actin, which is correlated to inhibition of phagosomal maturation. The effect of LPG on actin involves inhibition of PKCα and depends on active Rac1 and Cdc42.
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| 48. |
- Holm, Åsa, et al.
(author)
-
Leishmania donovani lipophosphoglycan causes periphagosomal actin accumulation : correlation with impaired translocation of PKCα and defective phagosome maturation
- 2001
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In: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 3:7, s. 439-447
-
Journal article (peer-reviewed)abstract
- Lipophosphoglycan (LPG) is the major surface glycoconjugate of Leishmania donovani promastigotes. The repeating disaccharide–phosphate units of LPG are crucial for promastigote survival inside macrophages and establishment of infection. LPG has a number of effects on the host cell, including inhibition of PKC activity, inhibition of nitric oxide production and altered expression of cytokines. LPG also inhibits phagosomal maturation, a process requiring depolymerization of periphagosomal F-actin. In the present study, we have characterized the dynamics of F-actin during the phagocytosis of L. donovani promastigotes in J774 macrophages. We observed that F-actin accumulated progressively around phagosomes containing wild-type L. donovani promastigotes during the first hour of phagocytosis. Using LPG-defective mutants and yeast particles coated with purified LPG, we obtained evidence that this effect could be attributed to the repeating units of LPG. LPG also disturbed cortical actin turnover during phagocytosis. The LPG-dependent accumulation of periphagosomal F-actin correlated with an impaired recruitment of the lysosomal marker LAMP1 and PKCα to the phagosome. Accumulation of periphagosomal F-actin during phagocytosis of L. donovani promastigotes may contribute to the inhibition of phagosomal maturation by physically preventing vesicular trafficking to and from the phagosome.
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| 49. |
- Holm, Åsa, et al.
(author)
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Lipid rafts are required for the effects of Leishmania donovani lipophosphoglycan on periphagosomal F-actin and phagosomal maturation
-
Other publication (other academic/artistic)abstract
- Lipophosphoglycan (LPG) is the major surface glycoconjugate on Leishmania donovani promastigotes, and is cmcial for pro mastigote survival following phagocytosis by macrophages. LPG consists of a chain of repeating phosphodisaccharides anchored to the parasite membrane by a lysophosphatidylinositol lipid anchor with an unusually long saturated fatty acid residue. During phagocytosis, LPG transfers from the parasite surface to the plasma membrane of the host macrophage. The presence of LPG alters the biophysical properties of the host cell membrane and the signaling capacity of the macrophage. LPG induces accumulation ofF-actin around the phagosome, and inhibits phagosome maturation. The effects of LPG on the host ce!l include inhibition of PKCα, a PKC isoenzyme involved in F-actin tumover.The biophysical properties of the LPG lipid anchor suggest that it partitions into caveolae or lipid rafts, which are cholesterol-rich plasma membrane microdomains central for signal transduction. Since PKCa is enriched in caveolae/lipid rafts in other cell types, we investigated if lipid rafts constitute a platform for the interaction of LPG and PKCα. We found that the plasma membrane of human monocyte-derived macrophages were rich in lipid rafts, but did not contain caveolae. LPG colocalized with lipid raft markers after interaction with WT L. donovani promastigotes. The presence of LPG inhibited the translocation of PKCα to the plasma membrane. Destruction of lipid rafts by cholesterol depletion lead to a complete eradication of LPG's effects on periphagosomal F-actin and phagosomal maturation. We also found that cholesterol depletion reduced uptake of WT L. donovani promastigotes, while uptake of an LPG-defective mutant was not affected.We conclude that LPG partitions to lipid rafts in the plasma membrane of human macrophages and inhibits the translocation of PKCα to the membrane. The presence of lipid rafts is a prerequisite for LPG to exert its effects on host cell actin and phagosomal maturation.
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| 50. |
- Holm, Åsa, 1969-, et al.
(author)
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Mechanical manipulation of polymorphonuclear leukocyte plasma membranes with optical tweezers causes influx of extracellular calcium through membrane channels
- 1999
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In: Medical and Biological Engineering and Computing. - 0140-0118 .- 1741-0444. ; 37:3, s. 410-412
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Journal article (peer-reviewed)abstract
- Optical tweezers are used mechanically to manipulate the plasma membrane of polymophonuclear leukocytes attached to the bottom of a glass manipulation chamber. The laser trapping beam is dragged across the membrane of cells in calcium-containing and calcium-depleted extracellular medium. This treatment causes a significant rise in the intracellular calcium concentration compared with controls, in cells in calcium-containing medium (239.8±49.0% against 75.4±16.4%, respectively), but not in cells in calcium-depeleted medium (69.1±9.6% against 83.4±18.5%, respectively), indicating that the calcium rise is caused by an influx of calcium from the environment. The rise in calcium concentration is blocked (23.5±7.1% against 17.1±4.1%, respectively) by the addition of lansoprazole, indicating that the influx is not due to unspecific membrane damage caused by the mechanical manipulation of the cell. It can therefore be concluded that mechanical manipulation of the neutrophil membrane, in the piconewton force range exerted by the optical tweezer, does not damage the plasma membrane but stimulates a mechanically inducible, membrane channel-mediated influx of extracellular calcium.
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