| 1. |
- Avdic, Tarik, et al.
(författare)
-
Risk Factors for and Risk of Peripheral Artery Disease in Swedish Individuals With Type 2 Diabetes: A Nationwide Register-Based Study.
- 2024
-
Ingår i: Diabetes care. - 1935-5548. ; 47:1, s. 109-116
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate to what extent having control of peripheral artery disease (PAD) risk factors is associated with the risk of incident PAD in individuals with type 2 diabetes.A total of 148,096 individuals with type 2 diabetes in the Swedish National Diabetes Register between 2005 and 2009 were included and matched with 320,066 control subjects on the basis of age, sex, and county. A few control subjects who developed type 2 diabetes after recruitment, during wash-in (<0.2%), were not censored but instead matched with two new control subjects. Individuals with type 2 diabetes were evaluated according to the number of PAD risk factors beyond recommended guideline levels at baseline, including LDL cholesterol, blood pressure, smoking, glycated hemoglobin, and estimated glomerular filtration rate. Incident PAD events were ascertained from 2006 to 2019.A graded association was observed between the number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes. The adjusted hazard ratio for PAD was 1.41 (95% CI 1.23-1.63) for those with type 2 diabetes with all PAD risk factors within target compared with control subjects matched for sex, age, and county but not risk factor status, in contrast with 9.28 (95% CI 3.62-23.79) for those with all five PAD risk factors not at target.A graded association was observed between increasing number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes.
|
|
| 2. |
- Consiglio, Camila, et al.
(författare)
-
Immune system adaptation during gender-affirming testosterone treatment
- 2023
-
Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 159, s. 29-30
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Biological sex impacts human immune responses, modulating susceptibility and severity to immune-related diseases. Female generally mount more robust immune responses than males, resulting in lower infection severity and greater autoimmunity incidence. Here, we addressed the contribution of testosterone to human immune function by analyzing a cohort of subjects undergoing gender-affirming testosterone treatment. We performed systems-level immunomonitoring through mass cytometry, scRNA and scA-TAC-Sequencing, and proteome profiling of blood samples at baseline and following 3 and 12 months of treatment. Testosterone treatment was associated with a low-grade inflammatory profile, evidenced by upregulation of proinflammatory plasma proteome (e.g., EN-RAGE, OSM, TNF), and induction of an inflammatory transcriptional program associated with NFkB signaling, and TNF signaling. Following testosterone treatment, higher NFkB activity was revealed in CD4 T, CD8 T, and NK cells in scATACseq analyses. Further, testosterone increased monocytic inflammatory responses upon bacterial stimulation in vitro. Although testosterone was associated with this inflammatory profile, it also exerted negative effects on antiviral immunity. Firstly, the percentage of plasmacytoid dendritic cells (pDC) decreased over transition, with pDC also displaying phenotypic changes associated with lower IFN responses. Secondly, bulk transcriptomics analyses show an overall reduction of IFNa responses. Thirdly, testosterone treatment led to reduced IFNa production upon PBMCs stimulation with a viral agonist. Our results show that testosterone has broad effects on the human immune system, and significantly modulates important players in antiviral immunity and inflammatory response. Identifying pathways involved in immune sexual dimorphism will help define novel targets for effective prevention and treatment of immune-mediated diseases.
|
|
| 3. |
- Ek, Hans, et al.
(författare)
-
Professioner, makt och samverkan mellan myndigheter : socialtjänstens, skolans och BUP:s arbete med ungdomar som inte går till skolan
- 2017
-
Ingår i: Socialvetenskaplig tidskrift. - Lund : Förbundet för forskning i socialt arbete (FORSA). - 1104-1420 .- 2003-5624. ; 24:1, s. 59-77
-
Tidskriftsartikel (refereegranskat)abstract
- School non-attendence is often a sign of a complex combination of different kinds of problems, which means that these children and young people are often in need of composite help from several different types of professions within various authorities. The purpose of the study was to examine how school authorities, the Social Services and Child and Adolescent Psychiatry (BUP) collaborate in their work with young people who do not go to school. The study comprised a thematic analysis of qualitative interviews with managerial representatives of the respective authorities. The empirical material consisted of 12 qualitative interviews with heads of units at BUP (5 individuals), section managers from Social Services (3 individuals) and principals from compulsory schools (4 individuals) in three municipalities in western Sweden. According to the results, it seems problematic to manage the positions of power that may arise in collaboration between the parties. A position of power thus implies the right to make a desicion as a profession as well as activities that are related to each other. The right to make a desicion means the mandate to determine which measures should be put in place for the young people and their families. This study also shows that the parties should develop a common knowledge base that is a combination of educational, social and psychiatric perspectives. The common knowledge base can reduce the risk of power imbalance between the parties.
|
|
| 4. |
- Ek, Hans, 1966-
(författare)
-
Psykiatriseringen av skolkaren : BUP och det institutionella omhändertagandet av ungdomar som inte går till skolan
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main aim of the thesis was to investigate the nature of as well as critically review the institutional care of young people who do not go to school.The thesis consists of four studies. The first three studies are based on different empirical materials such as electronical journals and administrative patient databases, qualitative interviews with social workers at Child and Adolescent Psychiatry (CAP), and with managerial representatives in School, social services and CAP. The fourth study is mainly theoretical and problematizes the results from the first three studies.The results show several problematic aspects in the institutional care of young truants. When young truants enters CAP, a quick, and sometimes without psychological investigation, categorization is made with psychiatric terminology in the form of a diagnosis, and medicines are prescribed as treatment. Further, social workers, who shall have a systemic approach on family and relationships, seem to embrace a psychiatric diagnostic understanding of the problems. At the same time, it appears that school only has extra resources to help the truants if they have a psychiatric diagnosis. Although the idea of collaboration between different professionals is that several different perspectives should be used, the results shows that CAP's psychiatric perspective dominates.The results of what happens to young people who do not go to school is discussed as an example of a special form of medicalization, in which social difficulties and existential problems are referred to psychiatry. It appears that help for them is completely individualised, by focusing on symptoms and diagnosis. What is not visible in this unilateral individualisation, for example, are organisational and educational problems in school, system problems in the family or among friends or lack of social contacts outside the family. By referring the truant to CAP can therefore miss further social circumstances in their life situation, which can have great importance in whether they attend school or not. Therefore, it is important to problematise this process of referring everything to psychiatry and to ask questions about what situations and events have contributed to this cultural pattern, which means that people's difficulties in life are increasingly being solved with diagnosis and medications.
|
|
| 5. |
- Forslund, Anders, 1982, et al.
(författare)
-
Bridging the gap between point cloud and CAD: A method to assess form error in aero structures
- 2016
-
Ingår i: 18th AIAA Non-Deterministic Approaches Conference, 2016; San Diego; United States; 4 January 2016 through 8 January 2016. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624103971
-
Konferensbidrag (refereegranskat)abstract
- One barrier to the successful implementation of probabilistic design methods is the lack of methods for characterizing form error. Form error, defined as the irregular deviations in geometry, is hard to describe in a virtual environment. This paper showcases a method that uses a simulation platform to assess the effects of form error on the aerodynamic, thermal and structural performance of an aero structure. Particularly, it looks at how bridging the gap between nominal CAD-geometries and point-cloud-based scanned geometries, creates a unified model where physical geometrical deviations can be isolated from model uncertainties. In a sample fatigue life problem, the effects of geometrically deviated parts is assessed. Further, a permutation genetic algorithm is implemented to optimize deviated part configuration. From a research standpoint, the showcased method contributes to addressing the genesis problem inherent in uncertainty quantification. From and industrial point of view, this method provides a precise, cost-effective tool for dealing with effects variations, which in turn increases both product quality and development process efficiency.
|
|
| 6. |
- Forslund, Anders, 1982, et al.
(författare)
-
Designing simulation platforms for uncertainty—An example from an aerospace supplier
- 2015
-
Ingår i: 17th AIAA Non-Deterministic Approaches Conference. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624103476 ; , s. 9-
-
Konferensbidrag (refereegranskat)abstract
- Variation poses a serious threat to the functionality, safety and reliability of aircraft. As the aerospace industry depends ever more heavily on modeling and simulation in their product development, there is an increased need to assess the effects of variation in a virtual environment. This paper outlines the methods proposed by a Swedish aerospace supplier to incorporate robust design methodology into platform-based product development. These methods evaluate how geometric variation affects the aerodynamic, thermal and structural performance of turbofan engine components. The results of the study show that simulation results are heavily affected by variations in geometry. Moreover, this study showcases automated simulation platforms as a powerful tool for robustness analyses. In addition to optimizing the robustness of products, these tools are equally effective as a tool for allocating engineering resources to optimize quality-to-cost ratio. © 2015 American Institute of Aeronautics and Astronautics Inc. All rights reserved.
|
|
| 7. |
- Forslund, Anders, 1982, et al.
(författare)
-
Evaluating How Functional Performance in Aerospace Components Is Affected by Geometric Variation
- 2018
-
Ingår i: SAE International Journal of Aerospace. - : SAE International. - 1946-3855 .- 1946-3901. ; 11:1, s. 5-26
-
Tidskriftsartikel (refereegranskat)abstract
- Geometric variation stemming from manufacturing can be a limiting factor for the quality and reliability of products. Therefore, manufacturing assessments are increasingly being performed during the early stages of product development. In the aerospace industry, products are complex engineering systems, the development of which require multidisciplinary expertise. In such contexts, there are significant barriers against assessing the effects of geometric variation on the functionality of products. To overcome these barriers, this article introduces a new methodology consisting of a modelling approach linked to a multidisciplinary simulation environment. The modelling approach is based on the parametric point method, which allows point-scanned data to be transferred to parameterised CAD models. In a case study, the methodology is implemented in an industrial setting. The capability of the methodology is demonstrated through a few applications, in which the effects of geometric variation on the aerodynamic, thermal, and structural performance of a load-bearing turbofan component are analysed. The proposed methodology overcomes many of the current barriers, making it more feasible to assess the effects of geometric variation during the early design phases. Despite some limitations, the methodology contributes to an academic understanding of how to evaluate geometric variation in multidisciplinary simulations and provides a tool for industry.
|
|
| 8. |
- Forslund, Anders, 1982, et al.
(författare)
-
MULTIDISCIPLINARY ROBUSTNESS EVALUATIONS OF AERO ENGINE STRUCTURES
- 2011
-
Ingår i: XX International Symposium on Air Breathing Engines 2011 (ISABE 2011), Proceedings of a meeting held 12-16 September 2011, Gothenburg, Sweden.
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a case study made to investigate the functional robustness of a jet engine turbine frame. Using virtual tools, a multidisciplinary analysis involving eight disciplines is performed on 50 non-nominal geometries. These geometries are obtained by varying the positions of the locators in the locating schemes on some parts of the assembly. Results show that geometrical variation can significantly affect the structural stresses on the product, and should thus be investigated further.
|
|
| 9. |
- Gennemark, Peter, et al.
(författare)
-
An oral antisense oligonucleotide for PCSK9 inhibition
- 2021
-
Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:593
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier-generation ASO chemistries and transient permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by N-acetylgalactosamine conjugation make this ASO highly potent. A single subcutaneous dose of 90 mg reduced PCSK9 by >90% in humans with elevated LDL cholesterol and a monthly subcutaneous dose of around 25 mg is predicted to reduce PCSK9 by 80% at steady state. To investigate the feasibility of oral administration, the ASO was coformulated in a tablet with sodium caprate as permeation enhancer. Repeated oral daily dosing in dogs resulted in a bioavailability of 7% in the liver (target organ), about fivefold greater than the plasma bioavailability. Target engagement after oral administration was confirmed by intrajejunal administration of a rat-specific surrogate ASO in solution with the enhancer to rats and by plasma PCSK9 and LDL cholesterol lowering in cynomolgus monkey after tablet administration. On the basis of an assumption of 5% liver bioavailability after oral administration in humans, a daily dose of 15 mg is predicted to reduce circulating PCSK9 by 80% at steady state, supporting the development of the compound for oral administration to treat dyslipidemia.
|
|
| 10. |
- Isaksson, Hanna, et al.
(författare)
-
High-fiber rye diet increases ileal excretion of energy and macronutrients compared with low-fiber wheat diet independent of meal frequency in ileostomy subjects
- 2013
-
Ingår i: Food & Nutrition Research. - Järfälla : Co-Action Publishing. - 1654-6628 .- 1654-661X. ; 57, s. 18519-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Whole-grain foods and cereal dietary fiber intake is associated with lower body weight. This may partly result from lower energy utilization of high-fiber diets. Objective: In the present study, the impact on ileal excretion of energy and macronutrients in response to a rye bread high-fiber diet compared to a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal frequency on apparent absorption of nutrients was studied for the first time. Design: Ten participants that had undergone ileostomy consumed standardized iso-caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2 weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks. The diets were consumed in an ordinary (three meals per day) and a nibbling (seven meals per day) meal frequency in a cross-over design. Ileal effluents were collected during 24 h at the third day of each of the four dietary periods and analyzed for gross energy and nutrient contents. Results: The results showed that intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet caused an increase in ileal excretion of energy and macronutrients. The effect was independent of meal frequency. This suggests that a high intake of rye may result in lower availability of macronutrients for small intestinal digestion and absorption. A regular intake of rye may therefore have implications for weight management.
|
|
| 11. |
- Landahl, Jonas, 1986, et al.
(författare)
-
Mediating constraints across design and manufacturing using platform-based manufacturing operations
- 2017
-
Ingår i: Proceedings of the International Conference on Engineering Design, ICED. - 2220-4334 .- 2220-4342. ; 6:DS87-6, s. 179-188
-
Konferensbidrag (refereegranskat)abstract
- To meet the needs of an array of customers, platforms can provide means to achieve commonality and distinctiveness among a family of products. However, typically the producibility of product variants are not ensured until the late platform development phases. This may lead to increased development lead-time, due to lack of integration across design and manufacturing. To be better suited in making early producibility assessments, a model to improve the integration across product platforms and manufacturing platforms is presented. The model is embodying manufacturing operations and marries platform models of two technical systems – products and manufacturing equipment. To serve the concurrency needed to explore cross product-manufacturing alternatives during the early phases of platform development, manufacturing operations can be modeled to serve improved integration of product platforms and manufacturing platforms. By modeling functions, control parameters, and key characteristics, the constraints across design and manufacturing can be mediated.
|
|
| 12. |
- Landahl, Jonas, 1986, et al.
(författare)
-
Using product and manufacturing system platforms to generate producible product variants
- 2016
-
Ingår i: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 44, s. 61-66
-
Konferensbidrag (refereegranskat)abstract
- Product platforms have proven efficient as a means to reduce lead-time and increase product quality simultaneously. When using platforms to generate a family of products, the number of variants that need to be managed in manufacturing increases. To succeed with this, the manufacturing system needs to be maintained in a similar level of flexibility as the product platform. However, there is seldom a joint decision behind each and every conceptual product variant during development, regarding capability in manufacturing. For example, when considering producibility, some product variants require better tolerances than what the manufacturing processes can deliver. This uncertainty can be reduced, by making producibility analyses of a set of conceptual product variants. By performing several different analyses, knowledge can be gained, and joint decisions can be made about cross product-manufacturing aspects. The activities can be systematically arranged to gradually eliminate unfeasible conceptual product variants. In this paper we show how an integrated PLM architecture can be used to create sufficient knowledge as a basis for joint product and manufacturing decisions. The utmost company benefit of this is to reduce lead-time by taking manufacturing capability into account when developing product families.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Panarotto, Massimo, 1985, et al.
(författare)
-
WORKING AGILE TO SPEED UP RESEARCH WITH INDUSTRY: FIVE INDEPENDENCE PRINCIPLES
- 2023
-
Ingår i: Proceedings of the Design Society. - 2732-527X. ; 3, s. 3919-3928
-
Konferensbidrag (refereegranskat)abstract
- One of the obstacles to the ability of research to make an impact on industry resides on the research process itself. Today, there is a need to accelerate the means for research to support industrial transformation. At the same time, there is the need to maintain scientific rigorousness, which often requires time. To solve this trade-off, this paper evaluates existing research approaches through the lenses of agile development. The analysis is based on a simulation of research process architectures, and on observations made over several research projects with industry. The results of this analysis highlight five light-but-sufficient rules of research project behavior to keep momentum, motivation and trust when doing research with industry. The paper demonstrates the use of these five rules in a research sprint conducted iwith two automotive OEMs.
|
|
| 16. |
- Vallhagen, Johan, et al.
(författare)
-
A framework for producibility and design for manufacturing requirements in a system engineering context
- 2013
-
Ingår i: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 11, s. 145-150
-
Konferensbidrag (refereegranskat)abstract
- Aircraft engine technology has evolved and matured over a 70 year period under a continous pressure to become more sustainable, fuel efficient, noise efficient, etc. while ensuring robustness and cost efficiency in production and product operation through life. This paper addresses how current challenges, trends and practices enable the introduction of competitive production and through life operation support into new aircraft engine products. Specifically, the area of structural jet engine sub-structures and components is addressed, where product optimization is dominated by weigth optimization, but also characterised by increased expectations of functionality. As a means, novel manufacturing processes are introduced, and one means is to adopt a so called fabrication approach, where the component is build based on assemlying sub-components with better controlled properties into a component using various joining technologies such as welding. The paper presents a framework based on tigther refining a systems engineering and requirements engineering approach that, combined with a set-based engineering approach, allow for building of re-useable and adaptable engineering methods. Through systematically building this framework, and making use of state of the art modeling and simulation technologies, the introduction of the novel technologies necessarily to increase the engine sub-system performance can be realized without compromizing risk and cost. The paper displays by example some of the challenges that successfully have been addressed, and also some remaining that currently drive development of new practises, methods and tools. In conclusion, a more integrated framework to tie a systems engineering approach with the use of advanced modeling and simulation technologies in a reuseable manner, is a way to balance between product performance and producibility. Still the area is undergoing intence development and challenges for research, development and practice still remain. © 2013 The Authors. Published by Elsevier B.V.
|
|
| 17. |
- van Pelt, Ward, et al.
(författare)
-
An iterative inverse method to estimate basal topography and initialize ice flow models
- 2013
-
Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 7:3, s. 987-1006
-
Tidskriftsartikel (refereegranskat)abstract
- We evaluate an inverse approach to reconstruct distributed bedrock topography and simultaneously initialize an ice flow model. The inverse method involves an iterative procedure in which an ice dynamical model (PISM) is run multiple times over a prescribed period, while being forced with space-and time-dependent climate input. After every iteration bed heights are adjusted using information of the remaining misfit between observed and modeled surface topography. The inverse method is first applied in synthetic experiments with a constant climate forcing to verify convergence and robustness of the approach in three dimensions. In a next step, the inverse approach is applied to Nordenskioldbreen, Svalbard, forced with height-and time-dependent climate input since 1300 AD. An L-curve stopping criterion is used to prevent overfitting. Validation against radar data reveals a high correlation (up to R = 0.89) between modeled and observed thicknesses. Remaining uncertainties can mainly be ascribed to inaccurate model physics, in particular, uncertainty in the description of sliding. Results demonstrate the applicability of this inverse method to reconstruct the ice thickness distribution of glaciers and ice caps. In addition to reconstructing bedrock topography, the method provides a direct tool to initialize ice flow models for forecasting experiments.
|
|
| 18. |
|
|
| 19. |
|
|
