| 1. |
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| 2. |
- Wiberg, Nana, et al.
(author)
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Infant outcome at four years of age after intrapartum sampling of scalp blood lactate for fetal assessment. A cohort study
- 2018
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
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Journal article (peer-reviewed)abstract
- Objective To correlate the value of lactate in fetal scalp blood at delivery and the outcomes of the offspring at four years of age. Methods Cases where scalp blood lactate was taken within sixty minutes before delivery were identified from the randomized trial "Determination of pH or lactate in fetal scalp blood in management of intrapartum fetal distress”. Data were grouped according to the generally accepted cutoffs for normality, pre-acidemia, acidemia and concentrations above mean +2 SD during the second stage. The outcome measures included gross-/fine motor function, vision, hearing, speaking and cognitive disorders, signs of central motor damage and referral to specialized pediatric services. Results 307 cases were available for final analyse. With normal scalp lactate concentration, the number of children with a diagnosed disorder was lower compared to the pre-acidemic/ acidemic groups, although the findings were only significant for fine motor dysfunction (p = 0.036). Elevated lactate values were significantly associated with increased risk for a poorer capacity of attention and understanding of instructions (OR 1.37, 95% CI 1.07–1.74), and for fine motor dysfunction (OR 1.22, 95% CI 1.00–1.49) at the age of four. Conclusion Higher levels of lactate in fetal scalp blood seems to be associated with increased risk of an aberrant developmental outcome at four years of age in some areas.
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| 3. |
- Andersson Granberg, Tobias, 1973-, et al.
(author)
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Using Semi-professionals in Emergency Response
- 2016
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In: Proceedings of the 13th International Conference on Information Systems for Crisis Response and Management. - 9788460879848 ; , s. 1-6
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Conference paper (other academic/artistic)abstract
- The term semi-professional can be used to denote occupational groups that do not have emergency response as their primary profession but who get additional responsibilities within rescue and response, e.g. by performing a first response or assisting the professional emergency services. In this study, four different groups of possible semi-professional resources are analyzed and compared. Similarities and differences between the four groups are discussed. Factors, important for the successful implementation of a cross-sector collaboration of this kind, are highlighted. The preliminary results show that all four groups have the potential to act as semi-professional resources within emergency response. Interestingly, the basic requirements are the same for all groups, despite different prerequisites.
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| 4. |
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| 5. |
- Berghauser Pont, Meta, 1972, et al.
(author)
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PST
- 2019
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Other publication (software/multimedia) (other academic/artistic)abstract
- PST is a tool for performing space syntax and regular accessibility analyses. It currently consists of two main parts - a C++ and Python library called Pstalgo and a plugin for the desktop application QGIS.PST is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version. The GNU General Public License is intended to guarantee your freedom to share and change all versions of a program--to make sure it remains free software for all its users.For latest download visit either the Chalmers publication page, or find "Releases" on the Github page.
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| 6. |
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| 7. |
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| 8. |
- Blennow Nordström, Erik, et al.
(author)
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Neuropsychological outcome after cardiac arrest : results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2023
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In: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 27:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.METHODS: This was a prospective case-control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes.RESULTS: Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ - 1 (at least borderline-mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ - 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = - 0.37, 95% confidence intervals [- 0.61, - 0.12]), verbal (MD = - 0.34 [- 0.62, - 0.07]), and visual/constructive functions (MD = - 0.26 [- 0.47, - 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = - 0.44 [- 0.82, - 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance.CONCLUSIONS: In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.
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| 9. |
- Blennow Nordström, Erik, et al.
(author)
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Neuropsychological outcome after cardiac arrest : A prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)
- 2020
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In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 20:1
-
Journal article (peer-reviewed)abstract
- Background: This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. Methods: This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses. Discussion: In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA. Trial registration: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018
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| 10. |
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| 11. |
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| 12. |
- Blennow Nordström, Erik, et al.
(author)
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Serum neurofilament light levels are correlated to long-term neurocognitive outcome measures after cardiac arrest
- 2022
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In: Brain Injury. - : Informa UK Limited. - 0269-9052 .- 1362-301X. ; 36:6, s. 800-809
-
Journal article (peer-reviewed)abstract
- Objective To explore associations between four methods assessing long-term neurocognitive outcome after out-of-hospital cardiac arrest and early hypoxic-ischemic neuronal brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the outcome methods. Methods An explorative post-hoc study was conducted on survivor data from the international Target Temperature Management after Out-of-hospital Cardiac Arrest trial, investigating serum NFL sampled 48/72-hours post-arrest and neurocognitive outcome 6 months post-arrest. Results Among the long-term surviving participants (N = 457), serum NFL (n = 384) was associated to all outcome instruments, also when controlling for demographic and cardiovascular risk factors. Associations between NFL and the patient-reported Two Simple Questions (TSQ) were however attenuated when adjusting for vitality and mental health. NFL predicted results on the outcome instruments to varying degrees, with an excellent area under the curve for the clinician-report Cerebral Performance Category (CPC 1-2: 0.90). Most participants were classified as CPC 1 (79%). Outcome instrument correlations ranged from small (Mini-Mental State Examination [MMSE]-TSQ) to strong (CPC-MMSE). Conclusions The clinician-reported CPC was mostly related to hypoxic-ischemic brain injury, but with a ceiling effect. These results may be useful when selecting methods and instruments for clinical follow-up models.
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| 13. |
- Blennow Nordström, Erik, et al.
(author)
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Validity of the IQCODE-CA : An informant questionnaire on cognitive decline modified for a cardiac arrest population
- 2017
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In: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 118, s. 8-14
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Journal article (peer-reviewed)abstract
- Aim: To examine the psychometric properties of a modified version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), for a cardiac arrest population (IQCODE-CA). Methods: The IQCODE-CA, a 26-item observer-reported questionnaire, was completed by informants, defined as relatives or close friends, of 268 out-of-hospital cardiac arrest (OHCA) survivors who participated in the Target Temperature Management trial in a scheduled follow-up 180 +/- 14 days after OHCA. Survivors completed the Mini Mental State Examination (MMSE), the Rivermead Behavioural Memory Test (RBMT) and the Hospital Anxiety and Depression Scale (HADS). An exploratory factor analysis was performed. Associations between IQCODE-CA results and demographic variables along with other instruments were calculated. Area under the curve (AUC) ratios were evaluated to examine discrimination. Results: The IQCODE-CA measured one factor, global cognitive decline, with high internal consistency (ordinal alpha = 0.95). Age, gender or education did not influence the IQCODE-CA score. Associations with performance-based measures of global cognitive function as well as anxiety and depression ranged from small to moderate (rs = -0.29 to 0.38). AUC ratios ranged from fair to good (0.72-0.81). According to the MMSE and RBMT, the optimal cut-off score to identify cognitive decline on the IQCODE-CA was 3.04. Using this value, 53% of the survivors were under the cut-off. Conclusions: The IQCODE-CA identified a large amount of survivors with possible cognitive problems, making it useful when screening for cognitive decline post-CA. Due to lower AUC ratios than desired, additional performance-based measures should be used to improve the overall screening methodology. (C) 2017 Elsevier B.V. All rights reserved.
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| 14. |
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| 15. |
- Bonagas, Nadilly, et al.
(author)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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In: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
-
Journal article (peer-reviewed)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 16. |
- Bratt, Ola, 1963, et al.
(author)
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Population-based Organised Prostate Cancer Testing: Results from the First Invitation of 50-year-old Men
- 2024
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In: European Urology. - 0302-2838 .- 1873-7560. ; 85:3, s. 207-214
-
Journal article (peer-reviewed)abstract
- Background: The European Union recently recommended evaluation of the feasibility of organised prostate cancer screening. In Sweden, regional population-based organised prostate cancer testing (OPT) programmes were introduced in 2020. Objective: To describe initial participation rates and diagnostic outcomes. Design, setting, and participants: The three most populated Swedish regions invited all men aged 50 yr to OPT by a letter in 2020–2022. Men with prostate-specific antigen (PSA) ≥3 ng/ml were referred for prostate magnetic resonance imaging (MRI). PSA assays differed across regions. Men with Prostate Imaging Reporting and Data System (PI-RADS) 1–3 and PSA density ≥0.15 ng/ml/cm3 or PI-RADS 4–5 were referred for a biopsy. Data were obtained from the Swedish Register for Organised Prostate Cancer Testing. Outcome measurements and statistical analysis: Overall and regional participation rates, PSA distributions, PI-RADS score distributions, cancer detection, and treatment were evaluated. Results and limitations: A total of 23 855 (35%) of 68 060 invited men participated; 696 (2.9%) had PSA ≥3 ng/ml, and of them, 306 (44%) had a biopsy indication and 221 (32%) had a biopsy. On biopsy, 93 (42%) had Gleason grade group ≥2 (0.39% of PSA-tested men) and 44 (20%) Gleason grade group 1 cancer. Most men with cancer had treatment with curative intent (70%) or were under active surveillance (28%). Across regions, proportions of men with PSA ≥3 ng/ml ranged from 2.3% to 4.0%, and those with PI-RADS score 4–5 ranged from 12% to 21%. A limitation is that results are applicable only to first testing of men in their early 50s. Conclusions: The OPT programmes are feasible with good compliance to the diagnostic pathway. The use of MRI and PSA density avoided a biopsy for over half of the men with PSA ≥3 ng/ml. Inter-regional differences in diagnostic outcomes show a need for standardisation of the diagnostic pathway's components. Patient summary: We report the diagnostic outcomes of inviting 68 000 50-yr-old men to organised prostate cancer testing.
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| 17. |
- Conti, David, V, et al.
(author)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 18. |
- Freischmidt, Axel, et al.
(author)
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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
- 2015
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In: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 18:5, s. 631-
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
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| 19. |
- Gasch, Tobias
(author)
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Concrete as a multi-physical material with applications to hydro power facilities
- 2016
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Licentiate thesis (other academic/artistic)abstract
- During its lifetime, a concrete structure is subjected to many different actions, ranging from mechanical loads to environmental actions. To accurately predict its integrity from casting and throughout its service life, a modelling strategy is required that considers mechanical loading but also implicitly accounts for physical effects such as temperature and moisture variations. This is especially true for large concrete structures found in many infrastructure applications such as bridges, nuclear power plants and dams. Modelling concrete as a multi-physical material is becoming an increasingly used approach for which large research efforts are being made, including the development of more refined mathematical and numerical methods as well as considering more physical and chemical variables in the coupled model.The research project, of which this licentiate thesis is the first phase, aims at investigating aging concrete structures at hydro power facilities, with focus on the internal structures of the power plants. This thesis presents a review of advanced mathematical methods and concepts for modelling aging concrete found in the literature which can later be applied to study such structures. The focus is on models that describe the deformational behaviour of concrete where aspects such as aging, cracking, creep and shrinkage are investigated. However, in order to accurately describe such phenomena, a multi-physical approach is adopted where moisture and temperature variations in the concrete are studied. Also, models that describe the chemical behaviour related to hydration and thus in extension aging, are also reviewed and introduced in the multi-physical framework. The use of such models are discussed in the context of the finite element method (FEM), in which coupled models are implemented, verified and applied in the appended papers using two different FE codes.Several verification examples are presented covering different aspects of the implemented models, both in isolation and coupled in a multi-physical setting. By comparing the numerical results with experimental data from the literature it can be shown that it is possible to predict most aspects of aging concrete that have been of interest here. While these examples are all on a laboratory scale, numerical examples and case studies are also provided that exemplify how the models can be applied on a structural scale. By using the developed analysis tools, valuable information and insights can be gained on aging concrete structures and these tools will in the next phase of the research project be applied to large concrete structures at hydro power facilities.
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| 20. |
- Gasch, Tobias
(author)
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Multiphysical analysis methods to predict the ageing and durability of concrete
- 2019
-
Doctoral thesis (other academic/artistic)abstract
- With the societal demand for sustainability and the increasing age of infrastructure, a crucial task for the civil engineering community is to improve the durability of concrete structures. This thesis aims to contribute to such development through theoretical studies using mathematical modelling and numerical simulations. During its service life, a concrete structure is subjected to many different actions, ranging from mechanical loads to chemical and physical processes. Hence, a sound modelling strategy requires multiphysics and the inclusion of coupled chemical and physical fields (e.g. temperature, moisture and cement hydration) in addition to methods that describe mechanical integrity of the material. Conditions and phenomena critical for concrete structures at hydropower facilities have been of particular interest to study.The thesis presents several mathematical models of various complexity to describe the multiphysical behaviour of concrete using a material point description. A significant focus is on models that describe the mechanical behaviour of concrete where aspects such as ageing, cracking, creep and shrinkage are investigated. For the creep behaviour, a state-of-the-art model based on the Microprestress–Solidification (MPS) theory is reviewed and further developed. The appended papers (III to IV) presents a mathematical framework for the modelling of durability aspects of concrete based on multiphase porous media theory. The governing equations are derived with the Thermodynamically Constrained Averaging Theory (TCAT) as a starting point. It is demonstrated how this framework can be applied to a broad variety of phenomena related to durability; from the casting and hardening of concrete to the long-term absorption of water into air-entrained concrete. The Finite Element Methods (FEM) is used to solve the proposed mathematical models, and their capabilities are verified using experimental data from the literature.The main research contribution is the development and evaluation of theoretical models that advance the understanding and improve knowledge of the ageing and durability of concrete and concrete structures. More precisely, it is shown how multiphysical models and the developed multiphase framework can be used to gain insights on the material behaviour of concrete at smaller scales while they are also applicable to structural-scale simulations. During all model development, the efficient solution of structural problems has been fundamental. Through case studies and several examples from the literature, it is exemplified how these models can be used to enhance the performance and thereby increase the durability of concrete structures.
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| 21. |
- Gasch, Tobias, et al.
(author)
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Non-linear analyses of cracks in aging concrete hydro power structures
- 2016
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In: Dam Engineering. - : International Water Power & Dam Construction. - 0958-9341.
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Other publication (pop. science, debate, etc.)abstract
- The concrete structures at Swedish hydro power facilities were built during the early to mid-20th century and many of them are starting to exhibit age related wear and deterioration. It isimportant to ensure the integrity of these concrete structures from a dam safety perspectiveand also to secure a safe operation of the power facility in the future. With the latter in mind,this paper aims to study the concrete structures that house the power generating machinery ofthe facility, especially the parts close to the generator where the loads from the power unit aresupported. Cracks observed in these structures will reduce its stiffness, which affects theoperation of the rotating machinery. This paper presents and discusses some generalconsiderations and loads that are of importance for this type of structures and highlights sometypical cracks that have been observed in Swedish hydro power facilities. To complement thisdiscussion, a case study is presented of a hydro power facility where cracks have been foundin the concrete support structure of the power unit, especially at the interconnections betweenthe unit and the concrete. The most likely cause of these cracks are investigated through nonlinearfinite element analysis considering mechanical loads as well as physical loads such asdrying shrinkage and temperature variations. It is concluded that the long-term physicalloading is the most probable cause of the observed cracks. However, the operation of thepower unit and changes in its operational pattern can cause further propagation of thesecracks. Finally, suggestions on possible enhancement of the analysis methods used in the casestudy are proposed and discussed for further studies of this type of concrete structures.
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| 22. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(author)
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[Prostate cancer - diagnostics and screening]. : Prostatacancer – utredning, klinisk diagnostik och screening.
- 2024
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In: Lakartidningen. - 1652-7518. ; 121
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Journal article (peer-reviewed)abstract
- Prostate-specific antigen (PSA) based screening is controversial, even though randomised trials show that screening can reduce prostate cancer mortality. The main reason is that screening leads to overdiagnosis of indolent cancers that would never have surfaced clinically in the absence of screening. Recently, several large studies have shown that magnetic resonance imaging (MRI) improves prostate cancer diagnostics. With MRI, up to half of all men with elevated PSA values can be spared a biopsy. When a biopsy is needed, the needles can be directed towards the suspicious area in the prostate, which increases the detection of clinically significant tumors. In Sweden, regional programmes with organised prostate cancer testing were introduced in 2020. These programmes aim to make prostate cancer testing more standardized, efficient, and equitable. In the future, biomarkers and AI-based systems will likely be important to further improve prostate cancer diagnostics.
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| 23. |
- Griffiths, Jennifer R., et al.
(author)
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The importance of benthic-pelagic coupling for marine ecosystem functioning in a changing world
- 2017
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 23:6, s. 2179-2196
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Research review (peer-reviewed)abstract
- Benthic-pelagic coupling is manifested as the exchange of energy, mass, or nutrients between benthic and pelagic habitats. It plays a prominent role in aquatic ecosystems, and it is crucial to functions from nutrient cycling to energy transfer in food webs. Coastal and estuarine ecosystem structure and function are strongly affected by anthropogenic pressures; however, there are large gaps in our understanding of the responses of inorganic nutrient and organic matter fluxes between benthic habitats and the water column. We illustrate the varied nature of physical and biological benthic-pelagic coupling processes and their potential sensitivity to three anthropogenic pressures - climate change, nutrient loading, and fishing - using the Baltic Sea as a case study and summarize current knowledge on the exchange of inorganic nutrients and organic material between habitats. Traditionally measured benthic-pelagic coupling processes (e.g., nutrient exchange and sedimentation of organic material) are to some extent quantifiable, but the magnitude and variability of biological processes are rarely assessed, preventing quantitative comparisons. Changing oxygen conditions will continue to have widespread effects on the processes that govern inorganic and organic matter exchange among habitats while climate change and nutrient load reductions may have large effects on organic matter sedimentation. Many biological processes (predation, bioturbation) are expected to be sensitive to anthropogenic drivers, but the outcomes for ecosystem function are largely unknown. We emphasize how improved empirical and experimental understanding of benthic-pelagic coupling processes and their variability are necessary to inform models that can quantify the feedbacks among processes and ecosystem responses to a changing world.
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| 24. |
- Heimburg, Katarina, et al.
(author)
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Agreement between self-reported and objectively assessed physical activity among out-of-hospital cardiac arrest survivors.
- 2023
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In: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Low level of physical activity is a risk factor for new cardiac events in out-of-hospital cardiac arrest (OHCA) survivors. Physical activity can be assessed by self-reporting or objectively by accelerometery.AIM: To investigate the agreement between self-reported and objectively assessed physical activity among OHCA survivors HYPOTHESIS: Self-reported levels of physical activity will show moderate agreement with objectively assessed levels of physical activity.METHOD: Cross-sectional study including OHCA survivors in Sweden, Denmark, and the United Kingdom. Two questions about moderate and vigorous intensity physical activity during the last week were used as self-reports. Moderate and vigorous intensity physical activity were objectively assessed with accelerometers (ActiGraph GT3X-BT) worn upon the right hip for 7 consecutive days.RESULTS: Forty-nine of 106 OHCA survivors answered the two questions for self-reporting and had 7 valid days of accelerometer assessment. More physically active days were registered by self-report compared with accelerometery for both moderate intensity (median 5 [3:7] vs. 3 [0:5] days; p < 0.001) and vigorous intensity (1 [0:3] vs. 0 [0:0] days; p < 0.001). Correlations between self-reported and accelerometer assessed physical activity were sufficient (moderate intensity: rs = 0.336, p = 0.018; vigorous intensity: rs = 0.375, p = 0.008), and agreements were fair and none to slight (moderate intensity: k = 0.269, p = 0.001; vigorous intensity: k = 0.148, p = 0.015). The categorization of self-reported versus objectively assessed physical activity showed that 26% versus 65% had a low level of physical activity.CONCLUSION: OHCA survivors reported more physically active days compared with the results of the accelerometer assessment and correlated sufficiently and agreed fairly and none to slightly.
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| 25. |
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| 26. |
- Heimburg, Katarina, et al.
(author)
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Physical activity after cardiac arrest; protocol of a sub-study in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
- 2021
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In: Resuscitation Plus. - : Elsevier BV. - 2666-5204. ; 5
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Journal article (peer-reviewed)abstract
- Aims: The primary aim of this study is to investigate whether out-of-hospital cardiac arrest (OHCA) survivors have lower levels of self-reported physical activity compared to a non-cardiac arrest (CA) control group who had acute myocardial infarction (MI). Additional aims are to explore potential predictors of physical inactivity (older age, female gender, problems with general physical function, global cognition, mental processing speed/attention, anxiety symptoms, depression symptoms, kinesiophobia, fatigue), and to investigate the relationship between self-reported and objectively measured physical activity among OHCA-survivors. Methods: The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial) collects information regarding age, gender, self-reported physical activity, general physical function, global cognition and mental processing speed/attention at 6 months after OHCA. In this TTM2-trial cross-sectional prospective sub-study, participants at selected sites are invited to an additional follow-up meeting within 4 weeks from the main study follow-up. At this meeting, information regarding anxiety symptoms, depression symptoms, kinesiophobia and fatigue is collected. The OHCA-survivors are then provided with an objective measure of physical activity, a hip-placed accelerometer, to wear for one week, together with a training diary. At the end of the week, participants are asked to once again answer two self-reported questions regarding physical activity for that specific week. MI-controls attend a single follow-up meeting and perform the same assessments as the OHCA-survivors, except from wearing the accelerometer. We aim to include 110 OHCA-survivors and 110 MI-controls in Sweden, Denmark and the United Kingdom. Conclusion: The results from this sub-study will provide novel information about physical activity among OHCA-survivors.
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| 27. |
- Hill, Tobias, et al.
(author)
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SPRIT : Identifying horizontal gene transfer in rooted phylogenetic trees
- 2010
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In: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 10:1, s. 42-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Phylogenetic trees based on sequences from a set of taxa can be incongruent due to horizontal gene transfer (HGT). By identifying the HGT events, we can reconcile the gene trees and derive a taxon tree that adequately represents the species' evolutionary history. One HGT can be represented by a rooted Subtree Prune and Regraft (RSPR) operation and the number of RSPRs separating two trees corresponds to the minimum number of HGT events. Identifying the minimum number of RSPRs separating two trees is NP-hard, but the problem can be reduced to fixed parameter tractable. A number of heuristic and two exact approaches to identifying the minimum number of RSPRs have been proposed. This is the first implementation delivering an exact solution as well as the intermediate trees connecting the input trees. RESULTS: We present the SPR Identification Tool (SPRIT), a novel algorithm that solves the fixed parameter tractable minimum RSPR problem and its GPL licensed Java implementation. The algorithm can be used in two ways, exhaustive search that guarantees the minimum RSPR distance and a heuristic approach that guarantees finding a solution, but not necessarily the minimum one. We benchmarked SPRIT against other software in two different settings, small to medium sized trees i.e. five to one hundred taxa and large trees i.e. thousands of taxa. In the small to medium tree size setting with random artificial incongruence, SPRIT's heuristic mode outperforms the other software by always delivering a solution with a low overestimation of the RSPR distance. In the large tree setting SPRIT compares well to the alternatives when benchmarked on finding a minimum solution within a reasonable time. SPRIT presents both the minimum RSPR distance and the intermediate trees. CONCLUSIONS: When used in exhaustive search mode, SPRIT identifies the minimum number of RSPRs needed to reconcile two incongruent rooted trees. SPRIT also performs quick approximations of the minimum RSPR distance, which are comparable to, and often better than, purely heuristic solutions. Put together, SPRIT is an excellent tool for identification of HGT events and pinpointing which taxa have been involved in HGT.
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| 28. |
- Hoffmann, Thomas J., et al.
(author)
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Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa - such as genetics - can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10-8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment.
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| 29. |
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| 30. |
- Karlberg, Tobias, et al.
(author)
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14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface
- 2018
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3 beta: ExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.
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| 31. |
- Lilja, Gisela, et al.
(author)
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Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
- 2023
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In: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
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Journal article (peer-reviewed)abstract
- IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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| 32. |
- Malm, Richard, et al.
(author)
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Cracking in the concrete foundation for hydropower generators : Analyses of non-linear drying diffusion, thermal effects and mechanical loads
- 2013
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Reports (other academic/artistic)abstract
- An extensive program for improvement of the hydropower plants in Sweden is currently on-going. The aims are to secure future production and to maintain and further develop an already high dam safety.During inspection, cracks were discovered in the concrete foundation, near the stator and rotor spider supports, at some hydropower stations in Sweden. The cracks were believed to be related to the function of the stator supports and to new patterns of generator operation. In earlier times, the generators ran continuously, while nowadays there are many stops and starts, sometimes even several times during one day. The objective of this study is to understand the complex interaction between the power generating system (stator, rotor, turbine, etc.) and the supporting concrete structure. It is important from a dam safety perspective to determine the causes of the structural cracks that have been found in-situ.A three dimensional non-linear finite element model has been developed in order to analyse formation and propagation of the cracks. Several different load effects have been studied in this project in addition to the mechanical loads during operation. The new pattern of generator operation with several starts and stops lead for instance to variations in temperature which have been studied. Besides this, the uneven drying shrinkage of concrete has also been studied in this project. Thereby, the structural behaviour of a concrete foundation for the power generating system has been analysed taking into account the transient thermal and moisture gradients in combination with dead loads and some of the operational loads imposed to the foundation.The analyses shows that reinforced concrete structure that constitute a support to the generator is subjected to cracking due to the loads considered in this study, where the cracks near the supports are caused by a combination of mechanical loads, long-term drying shrinkage and temperature variations. The analyses showed that even after 20 years, the moisture content in the centre of the thicker part in the concrete foundation still had a high relative humidity. At the same time the concrete close to the free surfaces and the slender parts of the concrete foundation had reached the same relative humidity as the environment. Thereby, a large difference in drying shrinkage is obtained between different parts of the concrete foundation and thereby large forces due to restrain. The analyses showed that the drying shrinkage induced cracking inside the concrete foundation and especially close to the supports of the stator and the rotor spider which coincides with location of the cracks found in-situ.The results show that the cracks found in-situ can be simulated and explained with advanced numerical methods. The results also indicate that the dynamic effect from the loads caused by the power generating system have to be studied further, since a reduced structural stiffness due to cracking may result in larger loads imposed on the structure from the magnetic eccentricity and turbine imperfections or alternatively lead to a fatigue failure of for instance the reinforcement.
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| 33. |
- Manum, Bendik, et al.
(author)
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Improving GIS-based Models for Bicycling Speed Estimations
- 2019
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In: Transportation Research Procedia. - : Elsevier BV. - 2352-1465 .- 2352-1457. ; 42, s. 85-99
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Conference paper (peer-reviewed)abstract
- For reasons ranging from carbon emissions to public health, traffic planning as well as urban design aim to increase the modal share of bicycling on the cost of fossil fuel based commuting. However, most urban and traffic planning practices handle bicycling very schematically. Typically, tools for analyzing bicycling rely on fixed speed templates, paying little attention to the fact that bicycling speeds vary a lot depending on type of bicyclist and explicit properties of bicycle routes and the contexts of those routes. As long as very simplified assumptions form the basis for analysis, it is hard to make reliable comparisons of alternative proposals of urban form layouts and infrastructure investments. Therefore, from the perspective of traffic planning as well as from the perspective of urban planning and design, there is need for more refined methods for predicting bicycling speeds. This paper presents an outline for such a bicycling speed modelling tool. This work combines tools and measures from two recent bikeability modelling studies. One is an urban form based study of bicycle route networks, grasping issues related to geometrical directness of routes and various measures of accessibility and density. The other calculates likely speeds based on horizontal and vertical geometry of routes. The latter model uses an advanced statistical model to grasp dependence between adjacent road segments. The new combined model is estimated using GPS tracking of real bicycle trips in combination with GIS-based data of bicycle route networks and of the local contexts of the routes. More in detail, the new model includes parameters estimated for the following covariates: • route geometry (by slope and by horizontal curvature) • intersection impedances derived from type of junction (by presence of signal-crossings and by kinds of crossing streets categorized by amounts of traffic) • type of bicycle-route (bicycle lane in street, separate bicycle lane, combined walk- and bicycle lane or mixed-use streets) • kind of surface (smooth surface or gravel) • density of entrances along route (a proxy for slower bicycling due to urban/vibrant context) The modelling is based on so-called Markov-dependence, including that the covariates are used to estimate continuous speed profiles along entire routes, and not only average speed levels on road segments seen separate and independent. Through this, the new model results in more realistic speed estimations than the previous models. The paper presents the result from applying the tool on a sample of bicycle routes in Gothenburg and compares the results with analyses from previous models and with empirical data of bicycling along the same routes.
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| 34. |
- Marcus, Lars, 1962-, et al.
(author)
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Developing the spatial capital at the Stockholm Central Station
- 2012
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In: The Future of Cities and Regions. - : Springer Science+Business Media B.V.. - 9789400725188 ; , s. 297-322
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Book chapter (peer-reviewed)abstract
- This project concerns the most centrally located and spatially complex area in central Stockholm. It is located directly to the west of the internationally well-known Stockholm City area developed in the 1950s and 1960s. Presently significant reconstruction of the central station and its track areas is under way which will also open up a large new development area in one of the most attractive locations in Stockholm. For this project Spacescape, an architectural office specializing in analysis of urban space and urban development projects in relation to urban life qualities such as, attractiveness, public safety and retail support formed an integrated consultancy group together with architects and landscape architects, delivering evaluation and design support to the project. This concerned both an analysis of the current status of the area, including the spatially complex interior of the central station, as well as support and evaluation of the different stages in the proposal. The themes analysed included spatial capital (accessibility to the rest of the city, especially for people working and living in the city), pedestrian flows, wayfinding, recreational qualities and public safety. Through continuous analyses during the design process Spacescape were able to support the project in a direction providing greater benefits in these areas and telling images show how the new proposal could create a much better outcome than the current one.
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| 49. |
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| 50. |
- Nordström, Tobias
(author)
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Predicting prostate cancer : on the use of biomarkers in prostate cancer diagnostics
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Aims: The aims of this thesis work were to answer the following questions. Paper I: How prevalent is testing and retesting with prostate-specific antigen (PSA)?; Paper II: Is a genetic score based on single-nucleotide polymorphisms (SNPs) informative regarding the risk of prostate cancer (PCa) in men with low PSA?; Paper III: Are the commercially available tests Prostate Health Index (PHI) and the four-kallikrein panel comparable in aiding biopsy decisions?; Paper IV: Do commonly used medications affect PSA and the risk of PCa? Methods: In Paper I and Paper IV, the population-based PSA cohort STHLM0 was used together with registry-based data. Paper I described limited-duration point prevalence of testing and survival analysis describing retesting with PSA. Paper IV determined differences in PCa risk and PSA level among men using aspirin, statin, metformin or no medication. Paper II included 172 men with PSA at 1‒3ng/ml. Participants were invited according to their genetic score and underwent prostate biopsy. Risk of prostate cancer was assessed using logistic regression. Paper III included 531 men who had undergone a first prostate biopsy. Predictive models were compared using receiver-operating characteristics (ROC/AUC) and calculation of biopsies that could be avoided. Results: Paper I. During a 9-year study period, 46%, 68%, and 77% of men without previous PCa and aged 50–59 years, 60–69 years, and 70–79 years, respectively, had a PSA test. The probability of retesting with PSA was PSA- and age-dependent, with a 26-month cumulative incidence of 0.34 if the first PSA value was < 1 ng/ml. Paper II. PCa was diagnosed in 47 of 172 men with PSA levels of 1‒3ng/ml (27%), with Gleason sum of ≥ 7 in 10 of them (5.8%). There was an increase in the odds ratio of 1.60 with increasing genetic risk score. The absolute difference in risk of positive biopsy was 19 percentage points, comparing the high and low genetic risk groups (37% vs. 18%). Paper III. The four-kallikrein panel showed AUCs of 69.0 when predicting PCa of any grade and 71.8 when predicting high-grade cancer (Gleason score ≥ 7). Similar values were found for PHI (70.4 and 71.1, respectively). Both models had higher AUCs than a base model with PSA value and age. Using a 10% predicted risk of high-grade PCa by the four-kallikrein panel or PHI = 39 as cutoff for biopsy saved 29% of the biopsies performed, at a cost of delayed diagnosis for 10% of the men with highgrade cancer. Paper IV. There were no significant associations between aspirin or any antidiabetic medication and the risk of PCa. Men using any statin had an increased risk of both high-grade PCa and PCa overall (OR = 1.25; OR = 1.16). Compared to men without the medication, the level of the first PSA was lower in men using aspirin, statin, metformin, or insulin. Conclusions: Although screening for PCa is not recommended in Sweden, PSA testing in Stockholm County was high in men aged over 50 years. A risk score based on SNPs predicts biopsy outcome in previously unbiopsied men with PSA levels of 1–3 ng/ml. Furthermore, we found that two blood tests, the PHI and the four-kallikrein panel, performed similarly in predicting prostate biopsy outcome. Introduction of such risk stratification tools could increase the proportion of men being classified in line with their true risk of PCa. We found no protective effect of aspirin, statins, or antidiabetics in terms of overall risk of prostate cancer or high-grade cancer.
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