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1.
  • Pascual, Didac, et al. (author)
  • The missing pieces for better future predictions in subarctic ecosystems: A Torneträsk case study
  • 2021
  • In: Ambio. - : Springer. - 0044-7447 .- 1654-7209. ; 50:2, s. 375-392
  • Research review (peer-reviewed)abstract
    • Arctic and subarctic ecosystems are experiencing substantial changes in hydrology, vegetation, permafrost conditions, and carbon cycling, in response to climatic change and other anthropogenic drivers, and these changes are likely to continue over this century. The total magnitude of these changes results from multiple interactions among these drivers. Field measurements can address the overall responses to different changing drivers, but are less capable of quantifying the interactions among them. Currently, a comprehensive assessment of the drivers of ecosystem changes, and the magnitude of their direct and indirect impacts on subarctic ecosystems, is missing. The Torneträsk area, in the Swedish subarctic, has an unrivalled history of environmental observation over 100 years, and is one of the most studied sites in the Arctic. In this study, we summarize and rank the drivers of ecosystem change in the Torneträsk area, and propose research priorities identified, by expert assessment, to improve predictions of ecosystem changes. The research priorities identified include understanding impacts on ecosystems brought on by altered frequency and intensity of winter warming events, evapotranspiration rates, rainfall, duration of snow cover and lake-ice, changed soil moisture, and droughts. This case study can help us understand the ongoing ecosystem changes occurring in the Torneträsk area, and contribute to improve predictions of future ecosystem changes at a larger scale. This understanding will provide the basis for the future mitigation and adaptation plans needed in a changing climate.
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  • Almobarak, Bilal, et al. (author)
  • Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype
  • 2023
  • In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 23:1
  • Journal article (peer-reviewed)abstract
    • BackgroundSmall intestinal neuroendocrine tumors (SI-NET) are highly differentiated and genetically stable malignant tumors, yet they often present with advanced metastatic spread at the time of diagnosis. In contrast to many other types of malignant tumors, primary SI-NET are often asymptomatic and typically smaller in size compared to adjacent lymph node metastases. This study explores the hypothesis that stimulating the chemosensing olfactory receptor 51E1 (OR51E1) decreases SI-NET proliferation suggesting a mechanism that explains a difference in proliferative rate based on tumor location.MethodsClinical data was used to address difference in tumor size depending on location. A SI-NET tissue microarray was used to evaluate expression of OR51E1 and olfactory marker protein (OMP). Primary cultured tumor cells from 5 patients were utilized to determine the effect of OR51E1 agonist nonanoic acid on metabolic activity. The SI-NET cell line GOT1 was used to determine effects of nonanoic acid on the transcriptome as well as long-term effects of nonanoic acid exposure with regards to cell proliferation, serotonin secretion, alterations of the cell-cycle and morphology.ResultsTumor size differed significantly based on location. OR51E1 and OMP were generally expressed in SI-NET. Primary SI-NET cells responded to nonanoic acid with a dose dependent altered metabolic activity and this was replicated in the GOT1 cell line but not in the MCF10A control cell line. Nonanoic acid treatment in GOT1 cells upregulated transcripts related to neuroendocrine differentiation and hormone secretion. Long-term nonanoic acid treatment of GOT1 cells decreased proliferation, induced senescence, and altered cell morphology.ConclusionOur results raise the possibility that exposure of intraluminal metabolites could represent a mechanism determining aspects of the SI-NET tumor phenotype. However, we could not causally link the observed effects of nonanoic acid exposure to the OR51E1 receptor.
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4.
  • Andersson, Fredrik, 1974-, et al. (author)
  • Female top management in family firms and non-family firms : Evidence from total population data
  • 2018
  • In: International Journal of Entrepreneurship and Small Business. - : InderScience Publishers. - 1476-1297 .- 1741-8054. ; 35:3, s. 303-326
  • Journal article (peer-reviewed)abstract
    • We exploit information on ownership, management and kinship to study the representation of women in top management teams in Swedish family and non-family firms among domiciled limited liability firms over the years 2004 to 2010. The share of female top managers is analysed across listed and non-listed firms as well as across industries. We then estimate the likelihood that a woman is elected into the top management team in family and non-family firms using a probit regression model where we control for firm- A nd individual-level characteristics, including the gender distribution of the firm and kinship relations to existing board members and firm owners. We find that non-listed family firms are more likely to appoint female top managers, whereas we find no differences among listed firms. Moreover, we find that the gender composition and kinship structures of firms influence the appointment of female top managers.
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5.
  • Andersson, Fredrik, 1974-, et al. (author)
  • The Characteristics and Performance of Family Firms : Exploiting information on ownership, governance and kinship using total population data
  • 2017
  • Reports (peer-reviewed)abstract
    • Family firms are often considered characteristically different from non-family firms, and the economic implications of these differences have generated significant academic debate. However, our understanding of family firms suffers from an inability to identify them in total population data, as this requires information on owners, their kinship and involvement in firm governance, which is rarely available. We present a method for identifying domiciled family firms using register data that offers greater accuracy than previous methods. We then apply it to data from Statistics Sweden concerning firm ownership, governance and kinship over the years 2004-2010. Next, we use Swedish data to estimate these firms’ economic contribution to total employment and gross domestic product (GDP) and compare them to private domiciled non-family firms in terms of their characteristics and economic performance. We find that the family firm is the prevalent organizational form, contributing to over one-third of all employment and GDP. Family firms are common across industries and sizes, ranging from the smallest producers to the largest multinational firms. However, their characteristics differ across sizes and legal forms, thereby indicating that the seemingly contradictory findings among previous studies on family firms may be due to unobserved heterogeneity. We furthermore find that they are smaller than private non-family firms in employment and sales and carry higher solidity, although they are more profitable. These differences diminish with firm size, however. We conclude that the term ‘family firm’ contains great diversity and call for increased attention to their heterogeneity.
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6.
  • Andersson, Fredrik, 1974-, et al. (author)
  • The Characteristics of Family Firms : Exploiting Information on Ownership, Kinship and Governance Using Total Population Data
  • 2018
  • In: Small Business Economics. - : Kluwer Academic/Plenum Publishers. - 0921-898X .- 1573-0913. ; 51:3, s. 539-556
  • Journal article (peer-reviewed)abstract
    • Family firms are often considered characteristically different from non-family firms. However, our understanding of family firms suffers from an inability to identify them in total population data; information is rarely available regarding owners, their kinship, and their involvement in firm governance. We present a method for identifying domiciled family firms using register data; this method offers greater accuracy than previous methods. We apply this method to Swedish data concerning firm ownership, governance, and kinship from 2004 to 2010. We find that the family firm is a significant organizational form, contributing over one third of all employment and gross domestic product (GDP). Family firms are common in most industries and range in size. Furthermore, we find that, compared to private non-family firms, family firms have fewer total assets, employment, and sales and carry higher solidity, although family firms are more profitable. These differences diminish with firm size. We conclude that the term “family firm” includes a large variety of firms, and we call for increased attention to their heterogeneity.
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7.
  • Ask, Urban, 1956, et al. (author)
  • IT Governance in the light of Paradox - A Social System Theory Perspective
  • 2006
  • In: The 40th Hawaii International Conference on System Sciences, 2007.
  • Conference paper (peer-reviewed)abstract
    • This paper uses Niclas Luhmann's concepts of paradox and deparadoxization as a starting point for looking at IT governance within large, Swedish organizations. All in all a total of 25 organizations within both the public and private sector have been investigated through interviews with the companies Chief Information Officers. The results are presented in relation to a number of areas within the study that could be identified as dichotomies, or areas where the respondents had to deal with conflicting logics. The results are discussed in general terms in relation to IT governance practice as well as the potential value of applying Luhmann's theory of social systems to the study of IT governance
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8.
  • Baldvinsdottir, Gudrun, 1962, et al. (author)
  • Accounting Research and Trust - A Literature Review
  • 2011
  • In: Qualitative Research in Accounting & Management. - : Emerald. - 1176-6093. ; 8:4, s. 382-424
  • Journal article (peer-reviewed)abstract
    • Purpose – The purpose of this paper is to provide a structured overview of literature in the nexus of trust and accounting. This can serve as a basis for future research, and thus provide a framework for asking more precise and focused research questions. Design/methodology/approach – All papers published in prominent accounting journals during a 15-year period were examined. Papers pertaining to the field of trust and accounting were categorized and analyzed in more detail, and qualitatively classified in accordance with selected dimensions. The review focused on papers explicitly exploring the link between accounting and trust. Findings – A large proportion of the papers is in the field of management accounting (MAN). The majority of published papers in the field are based on sociological theory, but there are some economics-based papers. Sociologically based analysis seems to provide more structure, but is also less paradigmatic in nature than economic theory. Only a small number of papers have an explicit definition of the concept of trust. The authors’ conclusion is that the state of research has been developing to become more paradigmatic in recent years. Originality/value – This is the only literature review that provides a comprehensive overview of research on trust and accounting. Thus, it is an aid to future research in the area.
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9.
  • Baldvinsdottir, Gudrun, 1962, et al. (author)
  • The Role of Trust in Accounting Research
  • 2003
  • In: 26th Annual Congress of the European Accounting Association, April 2-4, 2003 at the University of Seville, Spain.
  • Conference paper (peer-reviewed)abstract
    • The purpose of this paper is to present a review of the knowledge about the trust concept and its application within the accounting research context. This is done by examining the different ontological and epistemological assumptions that accounting research are based on, by relating these assumptions to various conceptions of trust used in accounting research, and by revealing the explicit and implicit role that is given to trust in accounting research. The review is based on articles published between 1995 and 2002 in eleven influential accounting journals. The results show that few accounting articles are explicitly related to trust. Our review supports observations regarding the absence of empirical research made in previous research. Our classification of epistemological and ontological assumptions resulted in an even distribution between the mainstream and alternative approaches. The use of trust in the selected articles showed four different types reflecting an increasing role of trust in explaining accounting phenomena. To summarise, our review produces a dissociated impression of the role of trust in accounting research.
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10.
  • Baldvinsdottir, Gudrun, 1962, et al. (author)
  • Trust Research in Accounting – A Literature Review
  • 2009
  • Reports (other academic/artistic)abstract
    • Purpose: The purpose of the paper is to provide a structured overview of literature in the nexus of trust and accounting. This can serve as a basis for future research, and thus provide a framework for asking more precise and focused research questions. Design/methodology/approach: All papers published in prominent accounting journals during a 10-year period were scanned. Papers pertaining to the field of trust and accounting were categorized and analyzed in more detail, and qualitatively classified in accordance with selected dimensions. The review was focused on papers explicitly exploring the link between accounting and trust. Findings: The greater part of the papers is in the field of management accounting. The majority of published papers in the field are based on sociological theory, but there are some economics-based papers. Sociologically-based analysis seems to provide more structure, but is also less paradigmatic in nature than economic theory. Only a minority of papers has an explicit definition of the concept of trust. Our conclusion is that the state of research is clearly non-paradigmatic in nature. Origininality/value: This is the only literature review that provides a comprehensive overview of research on trust and accounting. Thus, it is an aid in future research in the area.
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13.
  • Biel, Anders, 1948, et al. (author)
  • Emotions, Morality and Public Goods: The WTA-WTP Disparity Revisited
  • 2006
  • Reports (other academic/artistic)abstract
    • Empirical evidence suggests that people´s maximum willingness to pay for having a good is often substantially lower than their minimum willingness to accept not having it, and that this discrepancy tends to be especially large when valuing public goods. This paper hypothesizes that differences in emotions (e.g. regret) and moral perceptions can account for much of this discrepancy for public goods. A simple, real-money dichotomous-choice experiment is set up to test these hypotheses, which are largely supported.
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  • Biel, Anders, 1948, et al. (author)
  • The willingness to pay–willingness to accept gap revisited: The role of emotions and moral satisfaction
  • 2011
  • In: Journal of Economic Psychology. ; 32:6, s. 908-917
  • Journal article (peer-reviewed)abstract
    • While many earlier studies have found that people’s maximum willingness to pay for having a good is often substantially lower than their minimum willingness to accept not having it, more recent experimental evidence suggests that this discrepancy vanishes for standard consumption goods when an incentive-compatible design without misconceptions is used. This paper hypothesises that there is nevertheless a discrepancy for goods with a perceived moral character, such as contributions to a good cause, and moreover that the reason for this discrepancy can largely be explained by differences in emotions and moral perceptions. The results from a real-money dichotomous-choice experiment, combined with measurements of emotions and morality, are consistent with these hypotheses
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15.
  • Brynielsson, Joel, 1974-, et al. (author)
  • Analysis of Weak Signals for Detecting Lone Wolf Terrorists
  • 2012
  • In: Proceedings of the IEEE European Intelligence and Security Informatics Conference 2012 (EISIC 2012). ; , s. 197-204
  • Conference paper (peer-reviewed)abstract
    • Lone wolf terrorists pose a large threat to modern society. The current ability to identify and stop these kind of terrorists before they commit a terror act is limited since they are very hard to detect using traditional methods. However, these individuals often make use of Internet to spread their beliefs and opinions, and to obtain information and knowledge to plan an attack. Therefore, there is a good possibility that they leave digital traces in the form of weak signals that can be gathered, fused, and analyzed.In this work we present an analysis method that can be used to analyze extremist forums to profile possible lone wolf terrorists. This method is conceptually demonstrated using the FOI Impactorium fusion platform. We also present a number of different technologies that can be used to harvest and analyze information from Internet, serving as weak digital traces that can be fused using the suggested analysis method, in order to discover possible lone wolf terrorists.
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16.
  • Bylesjö, Max, et al. (author)
  • Integrated analysis of transcript, protein and metabolite data to study lignin biosynthesis in hybrid aspen
  • 2009
  • In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 8:1, s. 199-210
  • Journal article (peer-reviewed)abstract
    • Tree biotechnology will soon reach a mature state where it will influence the overall supply of fiber, energy and wood products. We are now ready to make the transition from identifying candidate genes, controlling important biological processes, to discovering the detailed molecular function of these genes on a broader, more holistic, systems biology level. In this paper, a strategy is outlined for informative data generation and integrated modeling of systematic changes in transcript, protein and metabolite profiles measured from hybrid aspen samples. The aim is to study characteristics of common changes in relation to genotype-specific perturbations affecting the lignin biosynthesis and growth. We show that a considerable part of the systematic effects in the system can be tracked across all platforms and that the approach has a high potential value in functional characterization of candidate genes.
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17.
  • Djärv, Tor, 1991, et al. (author)
  • Bayesian predictions for A=6 nuclei using eigenvector continuation emulators
  • 2022
  • In: Physical Review C. - 2469-9985 .- 2469-9993. ; 105:1
  • Journal article (peer-reviewed)abstract
    • We make ab initio predictions for the A=6 nuclear level scheme based on two- and three-nucleon interactions up to next-to-next-to-leading order in chiral effective field theory (χEFT). We utilize eigenvector continuation and Bayesian methods to quantify uncertainties stemming from the many-body method, the χEFT truncation, and the low-energy constants of the nuclear interaction. The construction and validation of emulators is made possible via the development of jupiterncsm - a new M-scheme no-core shell model code that uses on-the-fly Hamiltonian matrix construction for efficient, single-node computations up to Nmax=10 for Li6. We find a slight underbinding of He6 and Li6, although consistent with experimental data given our theoretical error bars. As a result of incorporating correlated χEFT-truncation errors we find more precise predictions (smaller error bars) for separation energies: Sd(Li6)=0.89±0.44MeV, S2n(He6)=0.20±0.60MeV, and for the beta decay Q value: Qβ-(He6)=3.71±0.65MeV. We conclude that our error bars can potentially be reduced further by extending the model space used by jupiterncsm.
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18.
  • Dwibedi, Chinmay Kumar, et al. (author)
  • Biological amplification of low frequency mutations unravels laboratory culture history of the bio-threat agent Francisella tularensis
  • 2020
  • In: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 45
  • Journal article (peer-reviewed)abstract
    • Challenges of investigating a suspected bio attack include establishing if microorganisms have been cultured to produce attack material and to identify their source. Addressing both issues, we have investigated genetic variations that emerge during laboratory culturing of the bacterial pathogen Francisella tularensis. Key aims were to identify genetic variations that are characteristic of laboratory culturing and explore the possibility of using biological amplification to identify genetic variation present at exceedingly low frequencies in a source sample. We used parallel serial passage experiments and high-throughput sequencing of F. tularensis to explore the genetic variation. We found that during early laboratory culture passages of F. tularensis, gene duplications emerged in the pathogen genome followed by single-nucleotide polymorphisms in genes for bacterial capsule synthesis. Based on a biological enrichment scheme and the use of high-throughput sequencing, we identified genetic variation that likely pre-existed in a source sample. The results support that capsule synthesis gene mutations are common during laboratory culture, and that a biological amplification strategy is useful for linking a F. tularensis sample to a specific laboratory variant among many highly similar variants.
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19.
  • Edberg, Andreas, 1974-, et al. (author)
  • Endocervical swabs transported in first void urine as combined specimens in the detection of Mycoplasma genitalium by real-time PCR
  • 2009
  • In: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 58, s. 117-120
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to determine whether a patient’s endocervical swab specimen can be transported in first void urine (FVU) as combined specimens for the detection of Mycoplasma genitalium by real-time PCR. The study also compared two different DNA extraction methods for observation of possible PCR inhibition. Three specimens, one endocervical swab specimen transported in 2-SP medium, one endocervical swab specimen transported in FVU and a FVU specimen, were collected from 329 women. All sample types underwent manual DNA extraction whereas in the DNA extraction study, 329 endocervical swab specimens transported in FVU were subjected to both manual Chelex and automated BioRobot M48 DNA extraction. A total of 100 endocervical swab specimens transported in FVU from patients PCR-negative for M. genitalium in the study were used in the PCR inhibition analysis. M. genitalium was detected in 25/329 (7.6 %) women. The endocervical swab specimens transported in 2-SP medium and transported in FVU were positive for M. genitalium in 17/25 (68 %) and 24/25 (96 %) women, respectively. The FVU specimens alone were positive for M. genitalium in 22/25 (88 %) women. In the DNA extraction study, M. genitalium DNA was detected in 24/329 (7.3 %) and 28/329 (8.5 %) of endocervical swab specimens transported in FVU subjected to manual Chelex extraction and automated BioRobot M48 extraction, respectively. Partial PCR inhibition was detected in 6% of samples subjected to manual Chelex extraction whereas no inhibition was detected with the automated BioRobot M48 extraction. Thus endocervical swab specimens transported in FVU demonstrate higher sensitivity than FVU specimens only and have considerably increased sensitivity compared with endocervical swab specimens transported in 2-SP medium for detection of M. genitalium DNA. Moreover, automated BioRobot M48 extraction was shown to be superior to a crude manual Chelex extraction, leaving no PCR inhibition and giving a slightly higher DNA yield and/or better sensitivity.
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20.
  • Ekström, Andreas, 1980, et al. (author)
  • Bayesian optimization in ab initio nuclear physics
  • 2019
  • In: Journal of Physics G-Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 46:9
  • Journal article (peer-reviewed)abstract
    • Theoretical models of the strong nuclear interaction contain unknown coupling constants (parameters) that must be determined using a pool of calibration data. In cases where the models are complex, leading to time consuming calculations, it is particularly challenging to systematically search the corresponding parameter domain for the best fit to the data. In this paper, we explore the prospect of applying Bayesian optimization to constrain the coupling constants in chiral effective field theory descriptions of the nuclear interaction. We find that Bayesian optimization performs rather well with low-dimensional parameter domains and foresee that it can be particularly useful for optimization of a smaller set of coupling constants. A specific example could be the determination of leading three-nucleon forces using data from finite nuclei or three-nucleon scattering experiments.
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21.
  • Galván, Ignacio Fdez., et al. (author)
  • OpenMolcas : From Source Code to Insight
  • 2019
  • In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 15:11, s. 5925-5964
  • Journal article (peer-reviewed)abstract
    • In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.
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  • Johansson, Andreas (author)
  • Deliberating Intractability : Exploring Prospects of Deliberative Democracy in Intractable Natural Resource Management Conflicts
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • The increasing prevalence of intractable conflicts over natural resources, which defy technocratic solutions, highlights an urgent need for states, managers, and practitioners to find democratic methods for addressing them. In the normative debate over the optimal approach to managing these conflicts, deliberative democracy has emerged as a leading theoretical framework, sparking a deliberative turn in both political theory and natural resource governance. While the normative value of deliberative democracy—where the public collaboratively shapes collective decisions through reasoned discourse under conditions of equality and fairness—is widely acknowledged, its practical effectiveness in addressing intractable natural resource conflicts, particularly its capacity to foster productive reframing outcomes conducive to legitimate decisions or agreements, remains uncertain. In response to these uncertainties, this thesis explores the potential of deliberative democracy in intractable natural resource conflicts, using Swedish mining governance and its associated intractable conflicts as the empirical setting. It employs a qualitative case study design rooted in an interpretive analytical paradigm to investigate the possibility of achieving deliberation and associated reframing outcomes among disputing actors, examine the extent to which and how the ideal of deliberative democracy has manifested within the governance system entwined with the conflicts, and explore the interplay between contextual factors, deliberation, and associated reframing outcomes.The thesis concludes that while achieving consensus or mutually accepted agreement through deliberation in intractable conflicts may be unlikely, it is possible, given strict adherence to deliberative design principles and significant contextual knowledge, to realize ideal deliberation and the outcome of meta-consensus. This outcome holds substantial value as it can transform intractable conflicts into structured and respectful disagreements, thereby clarifying the conflicts and their dividing lines. Consequently, it makes intractable situations more manageable, facilitating efforts to reach compromises when feasible and make trade-offs when they are not. Furthermore, the thesis shows that meta-consensus can endure amid ongoing conflict and heightened polarization. However, the thesis also concludes that ideal deliberation and meta-consensus may not be attainable in all conflict scenarios due to contextual barriers. Factors, including strained pre-conflict community relations rooted in historical state decisions, a lack of prior foundation for inter-group engagement, entrenched affiliations among participants, and obstacles within the institutional design of the governance system, were identified as impediments to the realization of ideal deliberation and its associated outcomes. The thesis also reaffirms the challenges of extending deliberative democracy beyond isolated forums to pre-existing governance systems. Notably, while the investigated governance system has demonstrated an increasing commitment to deliberative norms and practices, a discernible gap exists between the system's current state and the principles of deliberative democracy, suggesting a "business as usual" scenario rather than a transition toward a deliberative democratic governance system.In light of these findings, this thesis provides several suggestions for aligning the system and other comparable governance systems with the deliberative democratic norms they aspire to achieve. It also proposes several directions for future research. These include exploring how deliberative processes can be optimally tailored to meet the unique demands of different contexts, continuing efforts to identify and address institutional and other contextual enablers and barriers to deliberation at both the micro and system levels. Addressing system-level barriers is particularly important if deliberation is to flourish beyond isolated forums. Furthermore, recognizing that meta-consensus does not provide a direct resolution to conflicts and cannot be enabled under all conditions, it is essential to identify mechanisms for trade-offs or outcomes that are deemed fair and acceptable even by those who do not get their preferences realized. Additionally, acknowledging the possibility of harnessing long-term democratization effects of conflicts, more research to determine when and under what conditions conflicts and various non-democratic actions yield positive effects is crucial.
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23.
  • Johansson, Gustav, et al. (author)
  • Considerations and quality controls when analyzing cell-free tumor DNA
  • 2019
  • In: Biomolecular Detection and Quantification. - : Elsevier BV. - 2214-7535. ; 17
  • Journal article (peer-reviewed)abstract
    • Circulating cell-free tumor DNA (ctDNA) is a promising biomarker in cancer. Ultrasensitive technologies enable detection of low (< 0.1%) mutant allele frequencies, a pre-requisite to fully utilize the potential of ctDNA in cancer diagnostics. In addition, the entire liquid biopsy workflow needs to be carefully optimized to enable reliable ctDNA analysis. Here, we discuss important considerations for ctDNA detection in plasma. We show how each experimental step can easily be evaluated using simple quantitative PCR assays, including detection of cellular DNA contamination and PCR inhibition. Furthermore, ctDNA assay performance is also demonstrated to be affected by both DNA fragmentation and target sequence. Finally, we show that quantitative PCR is useful to estimate the required sequencing depth and to monitor DNA losses throughout the workflow. The use of quality control assays enables the development of robust and standardized workflows that facilitate the implementation of ctDNA analysis into clinical routine. © 2019 The Authors
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24.
  • Johansson, Gustav, et al. (author)
  • Monitoring circulating tumor DNA during surgical treatment in patients with gastrointestinal stromal tumors
  • 2021
  • In: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 20:12, s. 2568-2576
  • Journal article (peer-reviewed)abstract
    • The majority of patients diagnosed with advanced gastrointestinal stromal tumors (GISTs) are successfully treated with a combination of surgery and tyrosine kinase inhibitors (TKIs). However, it remains challenging to monitor treatment efficacy and identify relapse early. Here, we utilized a sequencing strategy based on molecular barcodes and developed a GIST-specific panel to monitor tumor-specific and TKI resistance mutations in cell-free DNA and applied the approach to patients undergoing surgical treatment. Thirty-two patients with GISTs were included, and 161 blood plasma samples were collected and analyzed at routine visits before and after surgery and at the beginning, during, and after surgery. Patients were included regardless of their risk category. Our GIST-specific sequencing approach allowed detection of tumor-specific mutations and TKI resistance mutations with mutant allele frequency < 0.1%. Circulating tumor DNA (ctDNA) was detected in at least one timepoint in nine of 32 patients, ranging from 0.04% to 93% in mutant allele frequency. High-risk patients were more often ctDNA positive than other risk groups (P < 0.05). Patients with detectable ctDNA also displayed higher tumor cell proliferation rates (P < 0.01) and larger tumor sizes (P < 0.01). All patients who were ctDNA positive during surgery became negative after surgery. Finally, in two patients who progressed on TKI treatment, we detected multiple resistance mutations. Our data show that ctDNA may become a clinically useful biomarker in monitoring treatment efficacy in patients with high-risk GISTs and can assist in treatment decision making.
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26.
  • Lango Allen, Hana, et al. (author)
  • Hundreds of variants clustered in genomic loci and biological pathways affect human height.
  • 2010
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
  • Journal article (peer-reviewed)abstract
    • Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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27.
  • Lindberg, Anne, et al. (author)
  • From COPD epidemiology to studies of pathophysiological disease mechanisms : challenges with regard to study design and recruitment process
  • 2017
  • In: European Clinical Respiratory Journal. - : Taylor & Francis. - 2001-8525. ; 4
  • Journal article (peer-reviewed)abstract
    • Background: Chronic obstructive pulmonary disease (COPD) is a largely underdiagnosed disease including several phenotypes. In this report, the design of a study intending to evaluate the pathophysiological mechanism in COPD in relation to the specific phenotypes non-rapid and rapid decline in lung function is described together with the recruitment process of the study population derived from a population based study.Method: The OLIN COPD study includes a population-based COPD cohort and referents without COPD identified in 2002–04 (n = 1986), and thereafter followed annually since 2005. Lung function decline was estimated from baseline in 2002–2004 to 2010 (first recruitment phase) or to 2012/2013 (second recruitment phase). Individuals who met the predefined criteria for the following four groups were identified; group A) COPD grade 2–3 with rapid decline in FEV1 and group B) COPD grade 2–3 without rapid decline in FEV1 (≥60 and ≤30 ml/year, respectively), group C) ever-smokers, and group D) non-smokers with normal lung function. Groups A–C included ever-smokers with >10 pack years. The intention was to recruit 15 subjects in each of the groups A-D.Results: From the database groups A–D were identified; group A n = 37, group B n = 29, group C n = 41, and group D n = 55. Fifteen subjects were recruited from groups C and D, while this goal was not reached in the groups A (n = 12) and B (n = 10). The most common reasons for excluding individuals identified as A or B were comorbidities contraindicating bronchoscopy, or inflammatory diseases/immune suppressive medication expected to affect the outcome.Conclusion: The study is expected to generate important results regarding pathophysiological mechanisms associated with rate of decline in lung function among subjects with COPD and the in-detail described recruitment process, including reasons for non-participation, is a strength when interpreting the results in forthcoming studies.
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30.
  • Schillemans, Tessa, et al. (author)
  • Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes – A nested case-control study
  • 2021
  • In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
  • Journal article (peer-reviewed)abstract
    • Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1–0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3–2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.
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31.
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32.
  • Svanberg, Christer, 1970, et al. (author)
  • Structural relaxations of phospholipids and water in planar membranes
  • 2009
  • In: Journal of Chemical Physics. - : AIP Publishing. - 1089-7690 .- 0021-9606. ; 130:3, s. 035101-
  • Journal article (peer-reviewed)abstract
    • We have used dielectric spectroscopy and temperature modulated differential scanning calorimetryTMDSC to investigate the structural relaxation processes and phase transitions of water and lipidsin multilamellar, planar phospholipids. At low hydration levels we observe the main structuralrelaxation related to the glass transition of the phospholipids. With increasing water content a morepronounced pretransition, attributed to a gel to ripple phase transition, is observed in the TMDSCdata. In the proximity of this pretransition, a distinct change in the temperature dependence oralternatively a bifurcation into two processes is observed in the dielectric data. Around thistemperature a crossover in the long-range ionic conductivity across the membranes is also observed,which is one of the key parameters for biological membranes. Thus, the major dynamical changesdo not occur at the main, i.e., the gel to liquid structural phase transition, but at a pretransition thatoccurs roughly 20 K below the main transition.
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33.
  • Vandenput, Liesbeth, 1974, et al. (author)
  • High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men.
  • 2016
  • In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 31:3, s. 683-689
  • Journal article (peer-reviewed)abstract
    • Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone-binding globulin (SHBG) associate with non-vertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the MrOS study had baseline estradiol and testosterone analyzed by GC-MS and SHBG by IRMA. Incident clinical vertebral fractures (n=242 cases) were evaluated in 4324 men during an average follow-up of 9.1 years. In a subsample of these men (n=2256), spine X-rays were obtained at baseline and after an average follow-up of 4.3 years to identify incident radiographic vertebral fractures (n=157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (HR per SD increase, 95% CI: 0.93, 0.80-1.08) nor testosterone (1.05, 0.91-1.21) predicted incident clinical vertebral fractures in age-adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12-1.37). This association remained significant after further adjustment for FRAX® with or without BMD. SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; OR per SD increase, 95% CI: 1.23, 1.05-1.44). This association remained significant after adjustment for FRAX® with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX® with BMD for vertebral fracture risk prediction. This article is protected by copyright. All rights reserved.
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