| 1. |
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| 2. |
- Currie, Andrew, et al.
(författare)
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The Impact of Enhanced Recovery Protocol Compliance on Elective Colorectal Cancer Resection Results From an International Registry
- 2015
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 261:6, s. 1153-1159
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ERAS (enhanced recovery after surgery) care has been shown in randomized clinical trials to improve outcome after colorectal surgery compared to traditional care. The impact of different levels of compliance and specific elements, particularly out with a trial setting, is poorly understood.Objective: This study evaluated the individual impact of specific patient factors and perioperative enhanced recovery protocol compliance on postoperative outcome after elective primary colorectal cancer resection.Methods: The international, multicenter ERAS registry data, collected between November 2008 and March 2013, was reviewed. Patient demographics, disease characteristics, and perioperative ERAS protocol compliance were assessed. Linear regression was undertaken for primary admission duration and logistic regression for the development of any postoperative complication.Findings: A total of 1509 colonic and 843 rectal resections were undertaken in 13 centers from 6 countries. Median length of stay for colorectal resections was 6 days, with readmissions in 216 (9.2%), complications in 948 (40%), and reoperation in 167 (7.1%) of 2352 patients. Laparoscopic surgery was associated with reduced complications [odds ratio (OR) = 0.68; P < 0.001] and length of stay (OR = 0.83, P < 0.001). Increasing ERAS compliance was correlated with fewer complications (OR = 0.69, P < 0.001) and shorter primary hospital admission (OR = 0.88, P < 0.001). Shorter hospital stay was associated with preoperative carbohydrate and fluid loading (OR = 0.89, P = 0.001), and totally intravenous anesthesia (OR= 0.86, P < 0.001); longer stay was associated with intraoperative epidural analgesia (OR = 1.07, P = 0.019). Reduced postoperative complications were associated with restrictive perioperative intravenous fluids (OR = 0.35, P < 0.001).Conclusions: This analysis has demonstrated that in a large, international cohort of patients, increasing compliance with an ERAS program and the use of laparoscopic surgery independently improve outcome.
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| 3. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 4. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 5. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 6. |
- Almgren, Magnus, 1972, et al.
(författare)
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The Nuts and Bolts of Deploying Process-Level IDS in Industrial Control Systems
- 2018
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Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : ACM. ; , s. 17-24
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Konferensbidrag (refereegranskat)abstract
- Much research effort has recently been devoted to securing Industrial Control Systems (ICS) in response to the increasing number of adverse incidents targeting nation-wide critical infrastructures. Leveraging the static and regular nature of the behavior of control systems, various data-driven methods that monitor the process-level network have been proposed as a defensive measure. Although these methods have been evaluated through offline analysis of ICS-related datasets, in absence of documented live experiments in real environments, a complete and global understanding of the applicability and efficiency of process-level monitoring is still lacking. In this work, we describe our experience of running a fully fledged intrusion detection system in an operational paper factory for 75 days. We discuss the nuts and bolts of running such systems in real environments and underline several practical challenges in meeting ICS-specific requirements. This work essentially aims at bridging the gap between ICS intrusion detection research and practice, and empirically validating the increasingly adopted data-driven approach to process-level monitoring.
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| 7. |
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| 8. |
- Bloomfield, Kim, et al.
(författare)
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Changes in Alcohol-Related Problems After Alcohol Policy Changes in Denmark, Finland, and Sweden
- 2010
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Ingår i: Journal of Studies on Alcohol and Drugs. - New Jersey : Rutgers, the State University of New Jersey. - 1937-1888. ; 71:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- Objective: European Union travelers' allowances for alcohol import to Denmark, Sweden, and Finland were abolished in 2004. In addition, excise taxes on alcohol were lowered in 2003 and 2005 in Denmark, and in 2004 in Finland. Using northern Sweden as a control site, this study examines whether levels of reported alcohol problems have changed in Denmark, Finland, and southern Sweden as a consequence of these policy changes. Method: Annual cross-sectional surveys were conducted in Denmark, Finland, and Sweden from 2003 to 2006. Five dependency items and seven extrinsic alcohol-related problems were examined. Changes were analyzed within each country/region with logistic regressions and tested for short- and long-term changes. Differential change was also tested between each country and the control site, northern Sweden. Results: Prevalence of alcohol problems decreased over the study period. Only in selected subgroups did problems increase. This mainly occurred in the samples for northern Sweden and Finland, and mostly among older age groups and men. In relation to the control site, however, no increases in problem prevalence were found. Conclusions: Our findings on a decline in reported alcohol problems largely agree with published reports on alcohol consumption over the same period in the study countries. They do not agree, however, with findings on changes in health and social statistics in Finland and Denmark, where some significant increases in alcohol-related harm have been found.
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| 9. |
- Cheung, Zeerim, et al.
(författare)
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Environment Effects in Organizational Form Emergence : The Origin of Two For-Profit Stock Exchanges
- 2017
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Konferensbidrag (refereegranskat)abstract
- This study sets out to advance our understanding on how organization environments induce highly embedded actors to take up new organizational forms. We conduct comparative historical study of two stock exchanges, Stockholm and Helsinki stock exchange, that became first and second in the world to take up the for-profit organizational model in 1993 and 1995 respectively. We use a large set of digitized archival data from the two settings to analyse organization environment incidents that developed in the two local settings and the organizational activities of the two stock exchanges. We found that external effects were moderated by local effects inducing organizational misfit to accumulate. Most interestingly we found that these environment-organization effects were exacerbated by peer interaction, joint exploratory work for a joint Nordic exchange, cross listings by firms, brokers starting operating at both stock exchanges, and regulatory harmonization work. This peer interaction induced analog competition and convergent guidelines for the new organizational form. Our contribution is to provide a nested model of environment effects on organization emergence and expose peer effects as previously unrecognized organization environment effects.
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| 10. |
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| 11. |
- Cheung, Zeerim, et al.
(författare)
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Peer Interaction and Pioneering Organizational Form Adoption: A tale of the first two for-profit stock exchanges
- 2022
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Ingår i: Organization Studies. - : SAGE Publications (UK and US). - 1741-3044 .- 0170-8406. ; 43:8, s. 1223-1246
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Tidskriftsartikel (refereegranskat)abstract
- Building on a historical case study on the first two stock exchanges to adopt the now globally dominant for-profit organizational form, the Stockholm Stock Exchange in 1993 and the Helsinki Stock Exchange in 1995, we argue that interaction among socially proximate peers contributes to pioneering organizational form adoption within an industry, particularly when such forms are introduced by established organizations. Peer interaction can induce a search for technically efficient organizational forms through the sharing of collective experiences, the establishment of collective assumptions, and a joint search for solutions. Together, these factors contribute to the legitimization of novel organizational forms in the local setting before the adoption of the first instantiation of those forms. We propose a context-sensitive multilevel model of peer-interaction-induced pioneering organizational form adoption that considers shared macro environmental drivers, idiosyncratic local environmental drivers, and peer interaction as central social mediators between the two. © The Author(s) 2021.
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| 12. |
- Chowdhury, Sohini Roy, et al.
(författare)
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Automated Augmentation with Reinforcement Learning and GANs for Robust Identification of Traffic Signs using Front Camera Images
- 2019
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Ingår i: Conference Record - Asilomar Conference on Signals, Systems and Computers. - 1058-6393. - 9781728143002 ; 2019-November, s. 79-83
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Konferensbidrag (refereegranskat)abstract
- Traffic sign identification using camera images from vehicles plays a critical role in autonomous driving and path planning. However, the front camera images can be distorted due to blurriness, lighting variations and vandalism which can lead to degradation of detection performances. As a solution, machine learning models must be trained with data from multiple domains, and collecting and labeling more data in each new domain is time consuming and expensive. In this work, we present an end-to-end framework to augment traffic sign training data using optimal reinforcement learning policies and a variety of Generative Adversarial Network (GAN) models, that can then be used to train traffic sign detector modules. Our automated augmenter enables learning from transformed nightime, poor lighting, and varying degrees of occlusions using the LISA Traffic Sign and BDD-Nexar dataset. The proposed method enables mapping training data from one domain to another, thereby improving traffic sign detection precision/recall from 0.70/0.66 to 0.83/0.71 for nighttime images.
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| 13. |
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| 14. |
- Enroth, Stefan, et al.
(författare)
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A strand specific high resolution normalization method for chip-sequencing data employing multiple experimental control measurements
- 2012
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Ingår i: Algorithms for Molecular Biology. - : Springer Science and Business Media LLC. - 1748-7188. ; 7, s. 2-
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-throughput sequencing is becoming the standard tool for investigating protein-DNA interactions or epigenetic modifications. However, the data generated will always contain noise due to e. g. repetitive regions or non-specific antibody interactions. The noise will appear in the form of a background distribution of reads that must be taken into account in the downstream analysis, for example when detecting enriched regions (peak-calling). Several reported peak-callers can take experimental measurements of background tag distribution into account when analysing a data set. Unfortunately, the background is only used to adjust peak calling and not as a preprocessing step that aims at discerning the signal from the background noise. A normalization procedure that extracts the signal of interest would be of universal use when investigating genomic patterns.Results: We formulated such a normalization method based on linear regression and made a proof-of-concept implementation in R and C++. It was tested on simulated as well as on publicly available ChIP-seq data on binding sites for two transcription factors, MAX and FOXA1 and two control samples, Input and IgG. We applied three different peak-callers to (i) raw (un-normalized) data using statistical background models and (ii) raw data with control samples as background and (iii) normalized data without additional control samples as background. The fraction of called regions containing the expected transcription factor binding motif was largest for the normalized data and evaluation with qPCR data for FOXA1 suggested higher sensitivity and specificity using normalized data over raw data with experimental background.Conclusions: The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously. Our evaluation on both synthetic and experimental data suggests that the method is successful in removing background noise.
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| 15. |
- Forsling, Robin, 1988-, et al.
(författare)
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Communication Efficient Decentralized Track Fusion Using Selective Information Extraction
- 2020
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Ingår i: Proceedings of the 23rd International Conference on Information Fusion (FUSION). - : Institute of Electrical and Electronics Engineers (IEEE). - 9780578647098 - 9781728168302
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Konferensbidrag (refereegranskat)abstract
- We consider a decentralized sensor network of multiple nodes with limited communication capability where the cross-correlations between local estimates are unknown. To reduce the bandwidth the individual nodes determine which subset of local information is the most valuable from a global perspective. Three information selection methods (ISM) are derived. The proposed ISM require no other information than the communicated estimates. The simulation evaluation shows that by using the proposed ISM it is possible to determine which subset of local information is globally most valuable such that both reduced bandwidth and high performance are achieved.
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| 16. |
- Forsling, Robin, 1988-, et al.
(författare)
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Conservative Linear Unbiased Estimation Under Partially Known Covariances
- 2022
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Ingår i: IEEE Transactions on Signal Processing. - : IEEE. - 1053-587X .- 1941-0476. ; 70, s. 3123-3135
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Tidskriftsartikel (refereegranskat)abstract
- Mean square error optimal estimation requires the full correlation structure to be available. Unfortunately, it is not always possible to maintain full knowledge about the correlations. One example is decentralized data fusion where the cross-correlations between estimates are unknown, partly due to information sharing. To avoid underestimating the covariance of an estimate in such situations, conservative estimation is one option. In this paper the conservative linear unbiased estimator is formalized including optimality criteria. Fundamental bounds of the optimal conservative linear unbiased estimator are derived. A main contribution is a general approach for computing the proposed estimator based on robust optimization. Furthermore, it is shown that several existing estimation algorithms are special cases of the optimal conservative linear unbiased estimator. An evaluation verifies the theoretical considerations and shows that the optimization based approach performs better than existing conservative estimation methods in certain cases.
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| 17. |
- Forsling, Robin, 1988-, et al.
(författare)
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Consistent Distributed Track Fusion Under Communication Constraints
- 2019
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Ingår i: Proceedings of the 22nd International Conference on Information Fusion (FUSION). - : IEEE. - 9780996452786 - 9781728118406
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Konferensbidrag (refereegranskat)abstract
- This paper addresses the problem of retrieving consistentestimates in a distributed network where the communication between the nodes is constrained such that only the diagonal elements of the covariance matrix are allowed to be exchanged. Several methods are developed for preserving and/or recovering consistency under the constraints imposed by the communication protocol. The proposed methods are used in conjunction with the covariance intersection method and the estimation performance is evaluated based on information usage and consistency. The results show that among the proposed methods, consistency can be preserved equally well at the transmitting node as at the receiving node.
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| 18. |
- Forsling, Robin, 1988-, et al.
(författare)
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Decentralized Data Fusion of Dimension-Reduced Estimates Using Local Information Only
- 2023
-
Ingår i: 2023 IEEE Aerospace Conference. - : IEEE. - 9781665490320 - 9781665490337
-
Konferensbidrag (refereegranskat)abstract
- This paper considers fusion of dimension-reduced estimates in a decentralized sensor network. The benefits of a decentralized sensor network include modularity, robustness and flexibility. Moreover, since preprocessed data is exchanged between the agents it allows for reduced communication. Nevertheless, in certain applications the communication load is required to be reduced even further. One way to decrease the communication load is to exchange dimension-reduced estimates instead of full estimates. Previous work on this topic assumes global availability of covariance matrices, an assumption which is not realistic in decentralized applications. Hence, in this paper we consider the problem of deriving dimension-reduced estimates using only local information. The proposed solution is based on an estimate of the information common to the network. This common information estimate is computed locally at each agent by fusion of all information that is either received or transmitted by that agent. It is shown how the common information estimate is utilized for fusion of dimension-reduced estimates using two well-known fusion methods: the Kalman fuser which is optimal under the assumption of uncorrelated estimates, and covariance intersection. One main theoretical result is that the common information estimate allows for a decorrelation procedure such that uncorrelated estimates can be maintained. This property is crucial to be able to use the Kalman fuser without double counting of information. A numerical comparison suggests that the performance degradation of using the common information estimate, compared to having local access to the actual covariance matrices computed by other agents, is relatively small.
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| 19. |
- Forsling, Robin, 1988-
(författare)
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Decentralized Estimation Using Conservative Information Extraction
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sensor networks consist of sensors (e.g., radar and cameras) and processing units (e.g., estimators), where in the former information extraction occurs and in the latter estimates are formed. In decentralized estimation information extracted by sensors has been pre-processed at an intermediate processing unit prior to arriving at an estimator. Pre-processing of information allows for the complexity of large systems and systems-of-systems to be significantly reduced, and also makes the sensor network robust and flexible. One of the main disadvantages of pre-processing information is that information becomes correlated. These correlations, if not handled carefully, potentially lead to underestimated uncertainties about the calculated estimates. In conservative estimation the unknown correlations are handled by ensuring that the uncertainty about an estimate is not underestimated. If this is ensured the estimate is said to be conservative. Neglecting correlations means information is double counted which in worst case implies diverging estimates with fatal consequences. While ensuring conservative estimates is the main goal, it is desirable for a conservative estimator, as for any estimator, to provide an error covariance which is as small as possible. Application areas where conservative estimation is relevant are setups where multiple agents cooperate to accomplish a common objective, e.g., target tracking, surveillance and air policing. The first part of this thesis deals with theoretical matters where the conservative linear unbiased estimation problem is formalized. This part proposes an extension of classical linear estimation theory to the conservative estimation problem. The conservative linear unbiased estimator (CLUE) is suggested as a robust and practical alternative for estimation problems where the correlations are unknown. Optimality criteria for the CLUE are provided and further investigated. It is shown that finding an optimal CLUE is more complicated than finding an optimal linear unbiased estimator in the classical version of the problem. To simplify the problem, a CLUE that is optimal under certain restrictions will also be investigated. The latter is named restricted best CLUE. An important result is a theorem that gives a closed form solution to a restricted best CLUE. Furthermore, several conservative estimation methods are described followed by an analysis of their properties. The methods are shown to be conservative and optimal under different assumptions about the underlying correlations. The second part of the thesis focuses on practical aspects of the conservative approach to decentralized estimation in configurations where the communication channel is constrained. The diagonal covariance approximation is proposed as a data reduction technique that complies with the communication constraints and if handled correctly can be shown to preserve conservative estimates. Several information selection methods are derived that can reduce the amount of data being transmitted in the communication channel. Using the information selection methods it is possible to decide what information other actors of the sensor network find useful.
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| 20. |
- Forsling, Robin, 1988-, et al.
(författare)
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Optimal Linear Fusion of Dimension-Reduced Estimates Using Eigenvalue Optimization
- 2022
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Ingår i: Proceedings of the 25th International Conference on Information Fusion (FUSION). - : IEEE. - 9781665489416 - 9781737749721
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Konferensbidrag (refereegranskat)abstract
- Data fusion in a communication constrained sensor network is considered. The problem is to reduce the dimensionality of the joint state estimate without significantly decreasing the estimation performance. A method based on scalar subspace projections is derived for this purpose. We consider the cases where the estimates to be fused are: (i) uncorrelated, and (ii) correlated. It is shown how the subspaces can be derived using eigenvalue optimization. In the uncorrelated case guarantees on mean square error optimality are provided. In the correlated case an iterative algorithm based on alternating minimization is proposed. The methods are analyzed using parametrized examples. A simulation evaluation shows that the proposed method performs well both for uncorrelated and correlated estimates.
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| 21. |
- Forsling, Robin, 1988-
(författare)
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The Dark Side of Decentralized Target Tracking : Unknown Correlations and Communication Constraints
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Using sensors to observe real-world systems is important in many applications. A typical use case is target tracking, where sensor measurements are used to compute estimates of targets. Two of the main purposes of the estimates are to enhance situational awareness and facilitate decision-making. Hence, the estimation quality is crucial. By utilizing multiple sensors, the estimation quality can be further improved. Here, the focus is on target tracking in decentralized sensor networks, where multiple agents estimate a common set of targets. In a decentralized context, measurements undergo local preprocessing at the agent level, resulting in local estimates. These estimates are subsequently shared among the agents for estimate fusion. Sharing information leads to correlations between estimates, which in decentralized sensor networks are often unknown. In addition, there are situations where the communication capacity is constrained, such that the shared information needs to be reduced. This thesis addresses two aspects of decentralized target tracking: (i) fusion of estimates with unknown correlations; and (ii) handling of constrained communication resources. Decentralized sensor networks have unknown correlations because it is typically impossible to keep track of dependencies between estimates. A common approach in this case is to use conservative estimators, which can ensure that the true uncertainty of an estimate is not underestimated. This class of estimators is pursued here. A significant part of the thesis is dedicated to the widely-used conservative method known as covariance intersection (CI), while also describing and deriving alternative methods for CI. One major result related to aspect (i) is the conservative linear unbiased estimator (CLUE), which is proposed as a general framework for optimal conservative estimation. It is shown that several existing methods, including CI, are optimal CLUEs under different conditions. A decentralized sensor network allows for less data to be communicated compared to its centralized counterpart. Yet, there are still situations where the communication load needs to be further reduced. The communication load is mostly driven by the covariance matrices since, in this scope, estimates and covariance matrices are shared. One way to reduce the communication load is to only exchange parts of the covariance matrix. To this end, several methods are proposed that preserve conservativeness. Significant results related to aspect (ii) include several algorithms for transforming exchanged estimates into a lower-dimensional subspace. Each algorithm corresponds to a certain estimation method, and for some of the algorithms, optimality is guaranteed. Moreover, a framework is developed to enable the use of the proposed dimension-reduction techniques when only local information is available at an agent. Finally, an optimization strategy is proposed to compute dimension-reduced estimates while maintaining data association quality.
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| 22. |
- Forsling, Robin, 1988-, et al.
(författare)
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Track-To-Track Association for Fusion of Dimension-Reduced Estimates
- 2023
-
Ingår i: Proceedings of the 26th International Conference on Information Fusion (FUSION). - : IEEE. - 9798890344854 - 9798350313208
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Konferensbidrag (refereegranskat)abstract
- Network-centric multitarget tracking under communication constraints is considered, where dimension-reduced track estimates are exchanged. Previous work on target tracking in this subfield has focused on fusion aspects only and derived optimal ways of reducing dimensionality based on fusion performance. In this work we propose a novel problem formalization where estimates are reduced based on association performance. The problem is analyzed theoretically and problem properties are derived. The theoretical analysis leads to an optimization strategy that can be used to partly preserve association quality when reducing the dimensionality of communicated estimates. The applicability of the suggested optimization strategy is demonstrated numerically in a multitarget scenario.
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| 23. |
- Gustafsson, Robin, et al.
(författare)
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Towards an Integrative Digital History Approach in Organization Studies
- 2016
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Ingår i: Academy of Management Proceedings. - : Academy of Management.
-
Konferensbidrag (refereegranskat)abstract
- Recent developments in digitizing of historical data and advances in software tools for structured analysis of digitized historical data, are creating opportunities to unleash previously untapped ways to use historical data. We build on recent suggestions for methodological integration, for outlining an integrative digital history approach, with the methodological rigor to unleash creative synthesis of business history and organization studies. Methodological integration constitutes an inter-meshing of methods that takes place already from the outset of the research process and remains so throughout the collection of sources, interpretation, and analysis. This places at the center a careful research design with a relational database for the collection and digitizing of data, structuring and coding of historical sources, historical interpretation, and analytics to be used. We outline key design issues, steps and processes for an integrative digital history approach. Following, we present the strengths of this approach in comparison to existing ‘analog’ business history and organizational studies methods. We end the paper by discussing future avenues and opportunities for digital history.
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| 24. |
- He, Qi, et al.
(författare)
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Mouse Breast Carcinoma Monocytic/Macrophagic Myeloid-Derived Suppressor Cell Infiltration as a Consequence of Endothelial Dysfunction in Shb-Deficient Endothelial Cells Increases Tumor Lung Metastasis
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:21
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Tidskriftsartikel (refereegranskat)abstract
- Metastasis reflects both the inherent properties of tumor cells and the response of the stroma to the presence of the tumor. Vascular barrier properties, either due to endothelial cell (EC) or pericyte function, play an important role in metastasis in addition to the contribution of the immune system. The Shb gene encodes the Src homology-2 domain protein B that operates downstream of tyrosine kinases in both vascular and immune cells. We have investigated E0771.lmb breast carcinoma metastasis in mice with conditional deletion of the Shb gene using the Cdh5-CreERt2 transgene, resulting in inactivation of the Shb-gene in EC and some hematopoietic cell populations. Lung metastasis from orthotopic tumors, tumor vascular and immune cell characteristics, and immune cell gene expression profiles were determined. We found no increase in vascular leakage that could explain the observed increase in metastasis upon the loss of Shb expression. Instead, Shb deficiency in EC promoted the recruitment of monocytic/macrophagic myeloid-derived suppressor cells (mMDSC), an immune cell type that confers a suppressive immune response, thus enhancing lung metastasis. An MDSC-promoting cytokine/chemokine profile was simultaneously observed in tumors grown in mice with EC-specific Shb deficiency, providing an explanation for the expanded mMDSC population. The results demonstrate an intricate interplay between tumor EC and immune cells that pivots between pro-tumoral and anti-tumoral properties, depending on relevant genetic and/or environmental factors operating in the microenvironment.
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| 25. |
- Jones, Owen R., et al.
(författare)
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Senescence rates are determined by ranking on the fast-slow life-history continuum
- 2008
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 11:7, s. 664-673
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analyses of survival senescence by using life tables have identified generalizations including the observation that mammals senesce faster than similar-sized birds. These generalizations have been challenged because of limitations of life-table approaches and the growing appreciation that senescence is more than an increasing probability of death. Without using life tables, we examine senescence rates in annual individual fitness using 20 individual-based data sets of terrestrial vertebrates with contrasting life histories and body size. We find that senescence is widespread in the wild and equally likely to occur in survival and reproduction. Additionally, mammals senesce faster than birds because they have a faster life history for a given body size. By allowing us to disentangle the effects of two major fitness components our methods allow an assessment of the robustness of the prevalent life-table approach. Focusing on one aspect of life history - survival or recruitment - can provide reliable information on overall senescence.
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| 26. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 27. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 28. |
- Karman, Tijs, et al.
(författare)
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Update of the HITRAN collision-induced absorption section
- 2019
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Ingår i: Icarus. - : Elsevier. - 0019-1035 .- 1090-2643. ; 328, s. 160-175
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Tidskriftsartikel (refereegranskat)abstract
- Correct parameterization of the Collision-induced Absorption (CIA) phenomena is essential for accurate modeling of planetary atmospheres. The HITRAN spectroscopic database provides these parameters in a dedicated section. Here, we significantly revise and extend the HITRAN CIA data with respect to the original effort described in Richard et al. [JQSRT 113, 1276 (2012)]. The extension concerns new collisional pairs as well as wider spectral and temperature ranges for the existing pairs. The database now contains CIA for N2N2, N2H2, N2-CH4, N2H2O, N2O2, O2O2, O2-CO2, CO2-CO2, H2H2, H2He, H2-CH4, H2H, HHe, CH4-CH4, CH4-CO2, CH4He, and CH4Ar collision pairs. The sources of data as well as their validation and selection are discussed. A wish list to eliminate remaining deficiencies or lack of data from the astrophysics perspective is also presented.
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| 29. |
- Langner, Taro, et al.
(författare)
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Uncertainty-Aware Body Composition Analysis with Deep Regression Ensembles on UK Biobank MRI
- 2021
-
Ingår i: Computerized Medical Imaging and Graphics. - : Elsevier BV. - 0895-6111 .- 1879-0771. ; 93
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Tidskriftsartikel (refereegranskat)abstract
- Along with rich health-related metadata, an ongoing imaging study has acquired MRI of over 40,000 male and female UK Biobank participants aged 44-82 since 2014. Phenotypes derived from these images, such as measurements of body composition, can reveal new links between genetics, cardiovascular disease, and metabolic conditions. In this retrospective study, six measurements of body composition were automatically estimated by ResNet50 neural networks for image-based regression from neck-to-knee body MRI. Despite the potential for high speed and accuracy, these networks produce no output segmentations that could indicate the reliability of individual measurements. The presented experiments therefore examine mean-variance regression and ensembling for predictive uncertainty estimation, which can quantify individual measurement errors and thereby help to identify potential outliers, anomalies, and other failure cases automatically. In 10-fold cross-validation on data of about 8,500 subjects, mean-variance regression and ensembling showed complementary benefits, reducing the mean absolute error across all predictions by 12%. Both improved the calibration of uncertainties and their ability to identify high prediction errors. With intra-class correlation coefficients (ICC) above 0.97, all targets except the liver fat content yielded relative measurement errors below 5%. Testing on another 1,000 subjects showed consistent performance, and the method was finally deployed for inference to 30,000 subjects with missing reference values. The results indicate that deep regression ensembles could ultimately provide automated, uncertainty-aware measurements of body composition for more than 120,000 UK Biobank neck-to-knee body MRI that are to be acquired within the coming years.
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| 30. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 31. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 32. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 33. |
- Mayo, Leah, et al.
(författare)
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Psychophysiological and Neural Support for Enhanced Emotional Reactivity in Female Adolescents With Nonsuicidal Self-injury
- 2021
-
Ingår i: Biological Psychiatry. - : Elsevier. - 2451-9022. ; 6:7, s. 682-691
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nonsuicidal self-injury (NSSI) is prevalent in adolescent populations worldwide. Emotion dysregulation is believed to contribute to NSSI, but underlying mechanisms are less known. We combined psychophysiological and neural data with subjective self-report in close temporal proximity to examine the mechanisms underlying emotion processing in adolescents with NSSI relative to control adolescents without a psychiatric diagnosis. METHODS: Thirty female adolescents with NSSI and 30 age-matched female control subjects were included in this case-control study. Participants were presented with negative affective pictures during a functional magnetic resonance imaging scan. In a separate facial electromyography session, the same participants were shown positive and negative affective images and also provided ratings of valence and arousal. RESULTS: Participants with NSSI responded to affective images with greater positive (e.g., zygomatic) and greater negative (e.g., corrugator) reactivity. We found no differences in self-reported affect in response to the images. Analyses of the negative picture-viewing functional magnetic resonance imaging data showed a significant positive correlation between anterior insula response and the averaged electromyography magnitude in NSSI, but not in control subjects. CONCLUSIONS: Adolescents with NSSI show enhanced emotional reactivity that is associated with anterior insula responding, but no abnormalities in self-reported affect. This discrepancy between self-report and objective measures of emotional reactivity potentially indicates a suppression of the emotional reaction in adolescents with NSSI. Moreover, the current data suggest potential targets for novel therapeutic approaches that can be combined with existing clinical treatment, such as real-time electromyography-based biofeedback focusing on emotional awareness, labeling, and expressing emotional experiences.
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| 34. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
-
Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 35. |
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| 36. |
- Mäkelä, Pia, et al.
(författare)
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Changes in volume of drinking after changes in alcohol taxes and travellers’ allowances: : results from a panel study
- 2007
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aims The aim of this paper is to study short-term changes in alcohol consumption by subgroups of the population in Denmark, Finland and southern Sweden following large-scale decreases in alcohol taxation in Denmark and Finland and large increases in travellers' allowances in Finland and Sweden. Design General population random samples surveyed before and after the changes, using northern Sweden as a control site. Setting Denmark, Finland, southern Sweden and northern Sweden. Participants Respondents aged 16-69 years. Measurements Volume of drinking is the main measure reported. Changes are examined by gender, age, income and year 2003 consumption level. Results Consumption decreased or remained the same among women and men in all three study sites. Relative changes were similar across subgroups of age, gender and income in all countries. In absolute terms, there was a consistent differential change by age in Denmark, Finland and Southern Sweden, with the higher level of the young and lower level of the old converging. Women's and men's consumption converged in Finland and southern Sweden. The changes did not differ systematically by income. Changes were not larger among heavier drinkers. Conclusions The results did not confirm expectations: an increase in consumption larger than that in the control site could not be shown in any of the countries or subgroups of the population. If there has been an effect - as shown in aggregate data in Finland - it seems to have been stronger among the old than the young and, in Finland and southern Sweden, among women rather than men.
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| 37. |
- Mäkelä, Pia, et al.
(författare)
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Changes in volume of drinking after changes in alcohol taxes and travellers' allowances : results from a panel study
- 2008
-
Ingår i: Addiction. - 0965-2140. ; 103:2, s. 181-191
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The Aim of this paper is to study short-term changes in alcohol consumption by subgroups of the population in Denmark. Finland and southern Sweden following large-scale decreases in alcohol taxation in Denmark and Finland and large increases in travellers' allowances in Finland and Sweden. Design General population random samples surveyed before and after the changes, using northern Sweden as a control site. Setting Denmark, Finland, southern Sweden and northern Sweden. Participants Respondents aged 16-69 years. Measurements Volume of drinking is the main measure reported. Changes are examined by gender, age, income and year 2003 consumption level. Results Consumption decreased or remained the same among women and men in all three study sites. Relative changes were similar across subgroups of age, gender and income in all countries. In absolute terms, there was a consistent differential change by age in Denmark, Finland and southern Sweden, with the higher level of the young and lower level of the old converging. Women's and men's consumption converged in Finland and southern Sweden. The changes did not differ systematically by income. Changes were not larger among heavier drinkers. Conclusions The results did not confirm expectations: an increase in consumption larger than that in the control site could not be shown in any of the countries or subgroups of the population. If there has been an effect - as shown in aggregate data in Finland - it seems to have been stronger among the old than the young and, in Finland and southern Sweden, among women rather than men.
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| 38. |
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| 39. |
- Nielsen, Jonas B., et al.
(författare)
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Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 102:1, s. 103-115
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10−18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10−11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.
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| 40. |
- Perini, Irene, et al.
(författare)
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Altered relationship between subjective perception and central representation of touch hedonics in adolescents with autism-spectrum disorder
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- An impairment of social communication is a core symptom of autism-spectrum disorder (ASD). Affective touch is an important means of social interaction, and C-Tactile (CT) afferents are thought to play a key role in the peripheral detection and encoding of these stimuli. Exploring the neural and behavioral mechanisms for processing CT-optimal touch (similar to 3 cm/s) may therefore provide useful insights into the pathophysiology of ASD. We examined the relationship between touch hedonics (i.e. the subjective pleasantness with which affective touch stimuli are perceived) and neural processing in the posterior superior temporal sulcus (pSTS). This region is less activated to affective touch in individuals with ASD, and, in typically developing individuals (TD), is correlated positively with touch pleasantness. TD and ASD participants received brushing stimuli at CT-optimal, and CT-non-optimal speeds during fMRI. Touch pleasantness and intensity ratings were collected, and affective touch awareness, a measure of general touch hedonics was calculated. As expected, slow touch was perceived as more pleasant and less intense than fast touch in both groups, whereas affective touch awareness was moderately higher in TD compared to ASD. There was a strong, positive correlation between right pSTS activation and affective touch awareness in TD, but not in ASD. Our findings suggest that altered neural coupling between right pSTS and touch hedonics in ASD may be associated with social touch avoidance in ASD.
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| 41. |
- Perini, Irene, et al.
(författare)
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Brain-based Classification of Negative Social Bias in Adolescents With Nonsuicidal Self-injury : Findings From Simulated Online Social Interaction.
- 2019
-
Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 13, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interpersonal stress and perceived rejection have been clinically observed as common triggers of nonsuicidal self-injury (NSSI), with self-injury behavior regulating both affective and social experiences. We investigated whether the subjective interpretation of social interaction in a simulated online environment might be biased in the NSSI group, and the brain mechanisms underlying the experience.Methods: Thirty female adolescent patients with NSSI and thirty female age-matched controls were investigated in this case-control study. In our novel task that simulates interaction on current social media platforms, participants indicated whether they liked or disliked pictures of other players during a functional magnetic resonance imaging (fMRI) scan. Participants also viewed positive and negative feedback directed toward them by others. The task also assessed the subjective effects of the social interaction. Finally, subjects underwent a separate facial electromyography session, which measured facial expressions processing.Outcomes: Behaviorally, the NSSI group showed a negative bias in processing social feedback from others. A multi-voxel pattern analysis (MVPA) identified brain regions that robustly classified NSSI subjects and controls. Regions in which mutual activity contributed to the classification included dorsomedial prefrontal cortex and subgenual anterior cingulate cortex, a region implicated in mood control. In the NSSI group, multi-voxel classification scores correlated with behavioral sensitivity to negative feedback from others. Results remained significant after controlling for medication, symptoms of depression, and symptoms of borderline personality disorder.Interpretation: This study identified behavioral and neural signatures of adolescents with NSSI during social interaction in a simulated social media environment. These findings highlight the importance of understanding social information processing in this clinical population and can potentially advance treatment approaches.
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| 42. |
- Perini, Irene, 1983-, et al.
(författare)
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Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation
- 2023
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Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; :6, s. 2563-2571
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Tidskriftsartikel (refereegranskat)abstract
- Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD. Four groups were defined across the dimensions of CM and lifetime SUD (N = 101 in total). After screening, participants completed two experimental sessions on separate days, aimed at assessing the behavioral, physiological, and neural mechanisms involved in emotion regulation. In the first session, participants engaged in tasks assessing biochemical (i.e., cortisol, endocannabinoids), behavioral, and psychophysiological indices of stress and affective reactivity. During the second session, the behavioral and brain mechanisms associated with emotion regulation and negative affect were investigated using magnetic resonance imaging. CM-exposed adults who did not develop SUD, operationally defined as resilient to developing SUD, had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress exposure, compared to controls. Similarly, this group had increased activity in salience and emotion regulation regions in task-based measures of emotion regulation compared to controls, and CM-exposed adults with lifetime SUD. At rest, the resilient group also showed significantly greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to controls and CM-exposed adults with lifetime SUD. Collectively, these peripheral and central findings point to mechanisms of potential resilience to developing SUD after documented CM exposure.
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| 43. |
- Perini, Irene, et al.
(författare)
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The salience of self, not social pain, is encoded by dorsal anterior cingulate and insula
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The human neural correlates of social rejection have attracted significant research interest, but remain subject to vigorous debate. Specifically, it has been proposed that a matrix of brain regions overlapping with the classical pain matrix, and including the dorsal anterior cingulate cortex (dACC) and the anterior insular cortex (AI) is critical for processing of social rejection. The present study expands on this conceptualization, by showing that these areas are involved in processing of self-relevant social evaluation, irrespective of valence. Forty healthy adolescents (N = 20 females) were tested in a magnetic resonance imaging (MRI) scanner. We used a novel paradigm that balanced participants experience of rejection and acceptance. In addition, the paradigm also controlled for whether the social judgment was towards the participants or towards other fictitious players. By creating a "self" and "other" distinction, we show that right AI and dACC are involved in processing the salience of being judged by others, irrespective of the quality of this judgment. This finding supports the idea that these regions are not specific to social rejection or even to pain or metaphorically painful experiences, but activate to self-relevant, highly salient information.
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| 44. |
- Rasmus, Sirpa, et al.
(författare)
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Observations and snow model simulations of winter energy balance terms within and between different coniferous forests in southern boreal Finland
- 2016
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Ingår i: Hydrology Research. - : Nordic Association for Hydrology. - 1998-9563 .- 0029-1277 .- 2224-7955. ; 47:1, s. 201-216
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Tidskriftsartikel (refereegranskat)abstract
- Variation of canopy properties between different forest types is seldom taken into account in hydrological and climate models, and consideration of variation inside a forest is normally omitted. In this work, three data sets on near surface energy balance terms (incoming shortwave and longwave radiation; air and snow-soil interface temperatures) were collected in the southern boreal coniferous zone in Finland during three winters below different types of forest canopies. The aim was to evaluate the ability of a snow mass and energy balance model with a canopy module to reproduce the observed differences in below-canopy incoming radiations and snow-soil interface temperature. Clear differences were seen between pine and spruce forest sites (higher snow-soil interface temperatures and incoming shortwave fluxes, and lower incoming longwave fluxes at the pine site). Differences were also observed between the sparse and dense pine canopy locations. Canopy parameter values had a great effect on the quality of the model simulations. The combination of optically obtained leaf area index (LAI) values with a needle clumping correction and either optical or empirical sky view fraction (SVF) values as a canopy parameterization gave better correspondence to observations than the use of uncorrected effective LAI and any SVF.
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| 45. |
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| 46. |
- Room, Robin, et al.
(författare)
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The frequency of drinking in different sites in different Nordic areas, and the effects on it of changes in alcohol availability
- 2008
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Ingår i: Nordic Studies on Alcohol and Drugs (NAT). - 1455-0725. ; 25:4, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- The site of drinking, as reported in population surveys in 2003 and 2004, was studied in Denmark, Finland and two areas of Sweden, in the north and the south. The aim of the study is to see whether there were differences in main sites of drinking between the four sites; to examine the effect of changes in price and availability due to major reductions in alcohol taxes in Finland and Denmark as well as increased traveler’s quotas on frequency of drinking in different sites; to see whether this effect varied for heavier drinkers; and to measure the stability of frequency of drinking in particular sites. The changes in availability affected Finland, Denmark and the southern area of Sweden. The north of Sweden is used as a control, as it was relatively unaffected by these changes. Probability samples aged 16-69 years were collected from all four sites through telephone interviews and postal questionnaires. The context questions concerned the frequency of drinking in restaurants or taverns, in the respondent’s own home, and in another person’s home. The most frequent location of drinking was usually one’s own home, particularly for those aged 30 and over. For younger Danes and Swedes, drinking in restaurants and other’s homes were also relatively frequent contexts for drinking. There were thus some differences between different Nordic areas in frequencies of drinking in different sites. However, there were few signs of substantial change between 2003 and 2004 in rates of drinking regularly in any of the contexts. Despite the changes in price and availability, the pre-existing differences in contexts of drinking thus stayed largely intact. This was true also among heavier drinkers. While there was substantial stability in all geographic areas between 2003 and 2004 in each respondent’s reported frequency of drinking in his or her own home, there was considerable variability from one year to the other in the frequencies of drinking in restaurants and on another’s house.
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| 47. |
- Room, Robin, et al.
(författare)
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What happened to alcohol consumption and problems in the Nordic countries when alcohol taxes were decreased and borders opened?
- 2013
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Ingår i: The international journal of alcohol and drug research. - : International Journal of Alcohol and Drug Research. - 1925-7066. ; 2:1, s. 77-87
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The study tests the effects of reduction in alcohol taxation and increased travellers’ allowances on alcohol consumption and related harm in Denmark, Finland and southern Sweden. In late 2003 and early 2004, taxes on alcoholic beverages were reduced in Denmark and Finland, and the abolition of quantitative quotas on alcohol import for personal use from other European Union countries made cheaper alcohol more available in Denmark, Finland and Sweden. Methods: Analyses of routine statistical register data, and summarizing results from longitudinal and repeated cross-sectional population surveys and other previous analyses, with northern Sweden as a control site for secular trends.Results: Contrary to expectations, alcohol consumption – as based on register data – increased only in Finland and not in Denmark and southern Sweden, and self-reported survey data did not show an increase in any site. In Finland, alcohol-attributable harms in register data increased, especially in people with low socio-economic status. Few such effects were found in Denmark and southern Sweden. Neither did results for self-reported alcohol-attributable problems show any general increases in the three sites. These results remained after controlling for regression to the mean and modelling of drop-outs.Conclusions: Harms measured in register data did tend to increase in the short term with the policy change, particularly in Finland, where the tax changes were broader. But reducing price and increasing availability does not always increase alcohol consumption and harm. Effects are dampened in affluent societies, and other factors may intervene. The results for Finland also suggest some limits for general population surveys in testing for relatively small policy effects.
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| 48. |
- Rosano, Giuseppe, et al.
(författare)
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COVID-19 vaccination in patients with heart failure: a position paper of the Heart Failure Association of the European Society of Cardiology
- 2021
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 23:11, s. 1806-1818
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Tidskriftsartikel (refereegranskat)abstract
- Patients with heart failure (HF) who contract SARS-CoV-2 infection are at a higher risk of cardiovascular and non-cardiovascular morbidity and mortality. Regardless of therapeutic attempts in COVID-19, vaccination remains the most promising global approach at present for controlling this disease. There are several concerns and misconceptions regarding the clinical indications, optimal mode of delivery, safety and efficacy of COVID-19 vaccines for patients with HF. This document provides guidance to all healthcare professionals regarding the implementation of a COVID-19 vaccination scheme in patients with HF. COVID-19 vaccination is indicated in all patients with HF, including those who are immunocompromised (e.g. after heart transplantation receiving immunosuppressive therapy) and with frailty syndrome. It is preferable to vaccinate against COVID-19 patients with HF in an optimal clinical state, which would include clinical stability, adequate hydration and nutrition, optimized treatment of HF and other comorbidities (including iron deficiency), but corrective measures should not be allowed to delay vaccination. Patients with HF who have been vaccinated against COVID-19 need to continue precautionary measures, including the use of facemasks, hand hygiene and social distancing. Knowledge on strategies preventing SARS-CoV-2 infection (including the COVID-19 vaccination) should be included in the comprehensive educational programmes delivered to patients with HF.
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| 49. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 50. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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