| 1. |
- Bergström, Göran, et al.
(author)
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Self-report tool for identification of individuals with coronary atherosclerosis : the Swedish cardiopulmonary bioimage study
- 2024
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In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:14
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Journal article (peer-reviewed)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly.CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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| 2. |
- Bergström, Göran, et al.
(author)
-
Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis : The Swedish CardioPulmonary BioImage Study
- 2024
-
In: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 13:14
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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| 3. |
- de Man Lapidoth, Julia, et al.
(author)
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Trends in renal function in Northern Sweden 1986-2014 : data from the seven cross-sectional surveys within the Northern Sweden MONICA study
- 2023
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:8
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Journal article (peer-reviewed)abstract
- Objective: The prevalence of chronic kidney disease (CKD) is increasing globally, and CKD is closely related to cardiovascular disease (CVD). CKD and CVD share several risk factors (RF), such as diabetes, hypertension, obesity and smoking, and the prevalence of these RF has changed during the last decades, and we aimed to study the effect on renal function over time.Design: Repeated cross-sectional population-based studies.Setting: The two Northern counties (Norr- and Vasterbotten) in Sweden.Participants: Within the MONitoring Trends and Determinants of CArdiovascular Disease (MONICA) study, seven surveys were performed between 1986 and 2014, including participants aged 25-64 years (n=10 185).Interventions: None.Measures: Information on anthropometry, blood pressure and cardiovascular risk factors was collected. Creatinine and cystatin C were analysed in stored blood samples and the estimated glomerular filtration rate (eGFR) calculated using the creatinine-based Lund-Malmo revised and Chronic Kidney Disease Epidemiology Collaboration (eGFR(crea)) equations as well as the cystatin C-based Caucasian, Asian, Paediatric and Adult cohort (CAPA) equation (eGFR(cysC)). Renal function over time was analysed using univariable and multivariable linear regression models.Results: Renal function, both eGFR(crea) and eGFR(cysC), decreased over time (both p<0.001) and differed between counties and sexes. In a multivariable analysis, study year remained inversely associated with both eGFR(crea) and eGFR(cysC) (both p<0.001) after adjustment for classical cardiovascular RF.Conclusion: Renal function has deteriorated in Northern Sweden between 1986 and 2014.
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| 4. |
- Khorsandi, Bahare M., et al.
(author)
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6G E2E Architecture Framework with Sustainability and Security Considerations
- 2022
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In: 2022 IEEE GLOBECOM Workshops, GC Wkshps 2022 - Proceedings. ; , s. 832-837
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Conference paper (peer-reviewed)abstract
- The research on 6G in the EU-funded flagship project Hexa-X started with the investigation of the most important technology enablers and the evaluation of relevant 6G use cases. The next step is to integrate these enablers in a 6G E2E architecture that fulfills all use case-based Key Performance (KPI) and Key Value Indicators (KVI) and that follows the guidelines of general architectural principles. In addition, the main focus of an E2E 6G architecture must be on security and sustainability which both will have increased importance for future communication networks and society.
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| 5. |
- Selva, Esteban, et al.
(author)
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Towards a 6G Embedding Sustainability
- 2023
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In: 2023 IEEE International Conference on Communications Workshops: Sustainable Communications for Renaissance, ICC Workshops 2023. ; , s. 1588-1593
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Conference paper (peer-reviewed)abstract
- From its conception, 6G is being designed with a particular focus on sustainability. The general philosophy of the H2020 Hexa-X project work on sustainability in 6G is based on two principles: to reduce direct negative life cycle impacts of 6G systems as much as possible (Sustainable 6G) and to analyze use cases that maximize positive environmental, social, and economic effects in other sectors of society (6G for Sustainability or its enablement effect). To apply this philosophy, Hexa-X is designing 6G with three sustainability objectives in mind: to enable the reduction of emissions in 6G-powered sectors of society, to reduce the total cost of ownership and to improve energy efficiency. This paper describes these objectives, their associated KPIs and quantitative targets, and the levers to reach them. Furthermore, to maximize the positive effects of 6G through the enablement effect, a link between 6G and the United Nations' Sustainable Development Goals (UN SDGs) framework is proposed and illustrated by Hexa-X use case families.
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| 6. |
- Svensson, Maria K., et al.
(author)
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A retrospective nationwide analysis of evolocumab use in Sweden and its effect on low-density lipoprotein cholesterol levels.
- 2024
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In: Upsala journal of medical sciences. - : Upsala Medical Society. - 2000-1967 .- 0300-9734. ; 129
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Journal article (peer-reviewed)abstract
- Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduces low-density lipoprotein cholesterol (LDL-C) levels and decreases the incidence of major ischaemic events in clinical trials. However, less is known about the efficacy of PCSK9 inhibition in clinical practice. This study aimed to describe the change in LDL-C levels over time and LDL-C goal achievement in patients with/without atherosclerotic cardiovascular disease (ASCVD), who were prescribed evolocumab in clinical practice, and to describe adherence to and persistence with treatment.Patients in Sweden with at least one evolocumab prescription filled between July 2015 and May 2020 were included. Medical history and lipid-lowering therapy (LLT) were sourced from national registries. LDL-C levels before and after treatment initiation were assessed using medical records. Persistence with and adherence to evolocumab and oral LLT were assessed up to 12 months after treatment initiation using the refill-gap method and proportion of days covered, respectively.Of the 2,360 patients with at least one prescription for evolocumab, 2,341 were included; 1,858 had ASCVD. Persistence with (76%) and adherence to (86%) evolocumab were high throughout the 12 months following initiation. Mean LDL-C levels decreased by 53% (95% confidence interval [CI]: 51-55%) in patients adherent to evolocumab (n = 567) and 59% (95% CI: 55-63%) in patients adherent to evolocumab and oral LLT (n = 186). Similar reductions in LDL-C were observed in patients with/without ASCVD. Reduced LDL-C levels remained stable during follow-up. Amongst patients adherent to evolocumab and those adherent to evolocumab and oral LLT, 23 and 55% achieved the LDL-C goal of <1.4 mmol/L, respectively.The evolocumab LDL-C-lowering effect observed in clinical trials was confirmed in clinical practice in Sweden, particularly in patients also treated with oral LLT. During follow-up, adherence to and persistence with evolocumab were high, with stable reduced levels of LDL-C during observation.
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| 7. |
- Tyler, Torbjörn, et al.
(author)
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Utsådda blommor räddar inte insekterna
- 2021
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In: Svenska Dagbladet. - 1101-2412.
-
Journal article (pop. science, debate, etc.)abstract
- Om vi vill rädda hotade insektsarter är det miljöer med traditionella ängsväxter som vi behöver mer av, inte fröblandningar av oklart ursprung från handeln. Det skriver flera debattörer.
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| 8. |
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| 9. |
- Akerblom, H., et al.
(author)
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Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study
- 2021
-
In: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 139:2, s. 200-205
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Journal article (peer-reviewed)abstract
- IMPORTANCE Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. OBJECTIVE To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. DESIGN, SETTING, AND PARTICIPANTS Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. EXPOSURE Gastric bypass surgery. MAIN OUTCOMES AND MEASURES Incidence of new DR and other diabetic ocular complications. RESULTS The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6%(1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5%(1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P <.001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. CONCLUSIONS AND RELEVANCE This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment. (c) 2021 American Medical Association. All rights reserved.
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| 10. |
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| 11. |
- Andersson Ersman, Peter, et al.
(author)
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Integration of Screen Printed Piezoelectric Sensors for Force Impact Sensing in Smart Multifunctional Glass Applications
- 2022
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In: Advanced Engineering Materials. - : John Wiley & Sons, Ltd. - 1438-1656 .- 1527-2648. ; 24:11
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Journal article (peer-reviewed)abstract
- Screen printed piezoelectric polyvinylidene fluoride?trifluoro ethylene (PVDF?TrFE)-based sensors laminated between glass panes in the temperature range 80?110?°C are presented. No degradation of the piezoelectric signals is observed for the sensors laminated at 110?°C, despite approaching the Curie temperature of the piezoelectric material. The piezoelectric sensors, here monitoring force impact in smart glass applications, are characterized by using a calibrated impact hammer system and standardized impact situations. Stand-alone piezoelectric sensors and piezoelectric sensors integrated on poly(methyl methacrylate) are also evaluated. The piezoelectric constants obtained from the measurements of the nonintegrated piezoelectric sensors are in good agreement with the literature. The piezoelectric sensor response is measured by using either physical electrical contacts between the piezoelectric sensors and the readout electronics, or wirelessly via both noncontact capacitive coupling and Bluetooth low-energy radio link. The developed sensor concept is finally demonstrated in smart window prototypes, in which integrated piezoelectric sensors are used to detect break-in attempts. Additionally, each prototype includes an electrochromic film to control the light transmittance of the window, a screen printed electrochromic display for status indications and wireless communication with an external server, and a holistic approach of hybrid printed electronic systems targeting smart multifunctional glass applications.
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| 12. |
- Andersson, M. L.E., et al.
(author)
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Pain in rheumatoid arthritis: a seven-year follow-up study of pain distribution and factors associated with transition from and to chronic widespread pain
- 2022
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; :51, s. 345-354
-
Journal article (peer-reviewed)abstract
- Objective: To study transitions from and to chronic widespread pain (CWP) over 7 years in patients with rheumatoid arthritis (RA). Method: Two postal questionnaires were sent to patients included in the BARFOT (Better Anti-Rheumatic Pharmacotherapy) study, the first in 2010 and the second in 2017. The questionnaires assessed pain, number of tender and swollen joints, functional disability, health-related quality of life (HRQoL), pharmacological treatment, lifestyle factors, and patient-reported body mass index (BMI). The responders to both questionnaires were divided into three groups according to the reported pain duration and distribution: patients having no chronic pain (NCP), chronic regional pain (CRP), and CWP. Results: In all, 953 patients answered the questionnaires at both time-points. One-third (324) of the patients reported CWP in 2010, and 140 (43%) of the patients had transition to NCP or CRP in 2017. In multivariate logistic regression models, adjusting for age, gender, and disease duration, transition from CWP was associated with normal BMI, fewer tender joints, less pain, less fatigue, fewer pain regions, less disability, better HRQoL, and biologic treatment. In 2010, 628 patients reported NCP or CRP, whereas 114 of them reported CWP in 2017. Transition to CWP was associated with female gender, obesity, more tender and swollen joints, higher pain-related variables, worse disability, and worse HRQoL. Conclusion: There are modifiable factors associated with transitions from and to CWP that could be identified. Paying attention to these factors could improve pain treatment in the management of RA.
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| 13. |
- Andersson, Stefan, FK, bibliotekarie, 1959-, et al.
(author)
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DiVA : 20 år av unikt samarbete
- 2021
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In: Uppsala universitetsbibliotek 1621–2021. - Uppsala : Acta Universitatis Upsaliensis. ; , s. 59-66
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Book chapter (pop. science, debate, etc.)
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| 14. |
- Andric, Stefan, et al.
(author)
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Performance, Analysis, and Modeling of III-V Vertical Nanowire MOSFETs on Si at Higher Voltages
- 2022
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In: IEEE Transactions on Electron Devices. - 0018-9383. ; 69:6, s. 3055-3055
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Journal article (peer-reviewed)abstract
- Heterostructure engineering in III-V vertical nanowire (VNW) MOSFETs enables tuning of transconductance and breakdown voltage. In this work, an InxGa 1−x As channel with a Ga-composition grading ( x= 1–0.4) in the channel and drain region, combined with field plate engineering, enables breakdown voltage above 2.5 V, while maintaining transconductance of about 1 mS/ μm , in VNW MOSFETs. The field plate consists of a vertically integrated SiO2 layer and a gate contact, which screens the electric field in the drain region, extending the device operating voltage. By scaling the field plate, a transconductance of 2 mS/ μm , alongside the breakdown voltage of 1.5 V, is obtained, demonstrating the benefit of field engineering in the drain. The scalability of the field plate and the gate is measured, showing an ON-resistance increase by 23 Ω⋅μm , and transconductance decrease by 5 μS/μm , per nm field plate length. This behavior is captured in a new and modified virtual source model, where device transmission and drain resistance are altered to capture the field plate scaling effect. The modeling is applied to nanowire (NW) devices with field plate lengths ranging from 5 to 115 nm, capturing accurately essential device performance parameters. Finally, a modified band-to-band (BTB) tunneling approach is used to accurately describe the device behavior above 1.5 V.
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| 15. |
- Attia, Zachi I., et al.
(author)
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Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram
- 2021
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In: Mayo Clinic proceedings. - : ELSEVIER SCIENCE INC. - 0025-6196 .- 1942-5546. ; 96:8, s. 2081-2094
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Journal article (peer-reviewed)abstract
- Objective: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG). Methods: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site. Results: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%. Conclusion: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control. (C) 2021 Mayo Foundation Medical Education and Research
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| 16. |
- Bergman, Filip, 1992-, et al.
(author)
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A Critical Review of the Sustainability of Multi-Utility Tunnels for Colocation of Subsurface Infrastructure
- 2022
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In: Frontiers in Sustainable Cities. - : Frontiers Media S.A.. - 2624-9634. ; 4
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Research review (peer-reviewed)abstract
- Multi-utility tunnel (MUT) have received increasing attention as an alternative method for installing subsurface infrastructure for the distribution of electricity, telecommunications, water, sewage and district heating. MUTs are described as a potentially more sustainable technology than conventional open-cut excavation (OCE), especially if the entire life cycle of these cable and pipe networks is taken into account. Based on an extensive review of the academic literature, this article aims to identify and critically examine claims made about the pros and cons of using MUT for the placement of subsurface infrastructure. Identified claims are mapped, and their validity and applicability assessed. These claims are then analyzed from a sustainability perspective, based on the three sustainability dimensions and a life cycle perspective. The results show that a variety of advantages and disadvantages of using MUTs for subsurface infrastructure are highlighted by the articles, but several of these are without any empirical support. When some form of empirical support is presented, it usually comes from case-specific analyses of MUTs, and the applicability in other MUT projects is seldom discussed. Economic performance is the sustainability dimension that has received the most attention, while environmental performance has not been analyzed in the reviewed literature, which is a major limitation of the current knowledge. In summary, the knowledge about the sustainability performance of using MUTs for subsurface infrastructure is still limited and incoherent. In order to increase the knowledge, this article points out the importance of new case studies, in which the sustainability consequences of using MUTs for subsurface infrastructure are mapped and evaluated by combining both quantitative and qualitative assessment methods.
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| 17. |
- Bergman, Filip, 1992-
(author)
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Sustainability performance of multi-utility tunnels : Sustainability assessments for furthering knowledge and understanding
- 2022
-
Licentiate thesis (other academic/artistic)abstract
- The multi-utility tunnel has received increased attention as an alternative method for the installation of subsurface infrastructure for the distribution of electricity, water, sewage and district heating. In previous research, the multi-utility tunnel (MUT) has been described as a more sustainable technology compared to the conventionally used technique where the cables and pipes are placed with open-cut excavation (OCE), especially when the entire life cycle is taken into account. This thesis aims to contribute to an improved understanding of MUT's sustainability performance in relation to conventional installation using open-cut excavation. This is done by using literature study, interview study and quantitative sustainability assessments to gain an understanding of the current state of knowledge. Furthermore, this thesis also focuses on how knowledge can be deepened with the help of quantitative sustainability assessments and the challenges of conducting this type of assessment. This thesis shows that the state of knowledge regarding MUT's sustainability performance is low and scattered, with a lack of a holistic approach. Direct economic performance has gained the most attention, followed by indirect and social impact, and the environmental impact has so far barely been assessed. The sustainability performance depends to a large extent on the conditions of the specific case, and these should be considered when assessing the technology. Quantitative assessments have the potential to help deepen the knowledge of the sustainability implications of using MUT. The characteristics of MUT have some similarities with other types of physical infrastructure. Similarities are that the systems are long-lived, have project conditions that affect sustainability performance, and impact a broad spectrum of actors. One difference to typical infrastructure systems is that the owner and management structure of MUT is, by design, more complex as several types of utility systems are in use. The characteristics of MUT give some practical considerations that need to be addressed: data availability, including practitioners; detailed data; transparency; and flexibility. This thesis highlights the complexity of assessing MUT´s sustainability performance and advocates that future studies should have a learning-oriented approach so that the knowledge level can collectively and gradually improve over time rather than focusing on decision-oriented studies.
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| 18. |
- Bjornsdottir, H. H., et al.
(author)
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A national observation study of cancer incidence and mortality risks in type 2 diabetes compared to the background population over time
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- We examined changing patterns in cancer incidence and deaths in diabetes compared to the background population. A total of 457,473 patients with type 2 diabetes, included between 1998 and 2014, were matched on age, sex, and county to five controls from the population. Incidence, trends in incidence and post-cancer mortality for cancer were estimated with Cox regression and standardised incidence rates. Causes of death were estimated using logistic regression. Relative importance of risk factors was estimated using Heller's relative importance model. Type 2 diabetes had a higher risk for all cancer, HR 1.10 (95% CI 1.09-1.12), with highest HRs for liver (3.31), pancreas (2.19) and uterine cancer (1.78). There were lesser increases in risk for breast (1.05) and colorectal cancers (1.20). Type 2 diabetes patients experienced a higher HR 1.23 (1.21-1.25) of overall post-cancer mortality and mortality from prostate, breast, and colorectal cancers. By the year 2030 cancer could become the most common cause of death in type 2 diabetes. Persons with type 2 diabetes are at greater risk of developing cancer and lower chance of surviving it. Notably, hazards for specific cancers (e.g. liver, pancreas) in type 2 patients cannot be explained by obesity alone.
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| 19. |
- 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-
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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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| 20. |
- Bosch-Sijtsema, Petra, 1971, et al.
(author)
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Kvalitet & Digitala Modeller: Integrerad kvalitetssäkring & automatiserade kvalitetskontroller i komplexa projekt
- 2022
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Reports (other academic/artistic)abstract
- Det finns stora effekter att vinna med digitalisering och BIM kopplat till projekterings- och byggprocessen. Att enkelt kunna identifiera och kontrollera att krav är uppfyllda är av stor vikt i multidisciplinära bygg- och anläggningsprojekt som ofta är komplexa och har många osäkerheter. Här anses BIM vara användbart för att bland annat förbättra kvaliteten genom att eliminera konflikter och minska omarbetningen. En styrd, kvalitetssäkrad och effektiv hantering av information om anläggningen kan rätt hanterat bland annat lämna ett ökat utrymme för innovation. Detta projekt presenterar en kartläggning över hur kvalitetssäkringsprocessen och kvalitetskontrollen genomförs idag och testar möjliga kvalitetskontroller. Genom att få en tydlig bild av hur kvalitetskontroller genomförs ges en inblick i de öar av kvalitetssäkringsprocessen som är generiska och vilka moment som kan automatiseras, vilket underlättar för alla aktörer och frigör tid för teknisk lösningsorienterade arbetsuppgifter och utveckling. Syftet med forskningsprojektet har varit att utveckla och testa kvalitetskontroller för kravuppfyllnad och kvalitetssäkring samt beslutsfattande kopplat till användande av digitala modeller. Projektet har genomförs baserat på ett Design Science angreppssätt vilket tar sin utgångspunkt i att både tekniska och mänskliga aspekter kopplas till det problem som ska lösas. Projektet uppdelades i 7 arbetspaket och är ett samarbete mellan Trafikverket, Chalmers, Trimble, Norconsult och Sweco. Del 1 i rapporten är en kartläggning av nuvarande process för leveranser, kvalitetssäkring och kravhantering inom projekteringsfasen, både hos Trafikverket och leverantör. Kartläggningen ger insyn i möjliga förbättringar och effektiviseringsvinster inom kvalitetssäkringsprocessen. Sammanfattningsvis visar kartläggningen att det behövs ett större fokus på de olika aktiviteterna som ingår i kvalitetsarbetet inom projekt. Del 2 i rapporten lyfter upp flera goda exempel och best-practices när det gäller automatiska kvalitetskontroller inom husbyggnad och menar att samma koncept för automatiska kvalitetskontroller går att använda inom anläggningsbranschen. Det finns extremt stor potential med automatiserade kvalitetskontroller (visuella, regelbaserade, automatiska och maskinläsbara) inom anläggningsprojekt och detta projekt har visat att det faktiskt fungerar och att det går att börja implementera vissa kontroller för digitala anläggningsmodeller redan nu. Dessa kontroller sparar tid och möjliggör att kontrollerna verkligen blir utförda. Dessutom kan dessa automatiska kvalitetskontroller frigöra tid som istället kan användas för att ta fram bättre tekniska lösningar och utformningar för projektet. Del 3 i rapporten tar upp en diskussion om kvalitetssäkring och digitala och/eller automatiserade kontroller. Utifrån innehåll i rapporten samlas här också ett antal rekommendationer relaterade till organisation, process och teknik/produkt. Rapporten tar upp att man för automatiserad kontroll av kravuppfyllnad vid leverander behövs ett modellorienterat integrerat arbetssätt för kontroll av lösning, en implementerad process för kvalitetssäkring av produktleveranser, ett modellbaserat gränssnitt för hantering av synpunkter och ändringar och en succeessiv uppföljning av projekt med en tillgänglig realtidsuppdaterad digital modell.
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| 21. |
- Brehm, Stefan, et al.
(author)
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Environmental governance with Chinese characteristics : are environmental model cities a good example for other municipalities?
- 2020
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In: Asia-Pacific Journal of Regional Science. - : Springer Science and Business Media LLC. - 2509-7946 .- 2509-7954. ; 4, s. 111-134
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Journal article (peer-reviewed)abstract
- Model programs such as the ‘environmental protection model city’ have become an inherent part of China’s urban environmental governance. The role of these incentive schemes for promoting best practice, however, has been neglected so far. In this study, we show that model city programs raise the bar in terms of environmental standards. What is more, model cities have a positive impact on regional economic development. We deploy a spatial Durbin model to measure best practice diffusion among 126 key environmental protection cities between 2009 and 2012. The results suggest that environmental model cities are better performers on average. We also find evidence for a positive spillover effect. Diffusion patterns are multi-layered where economic proximity is the most important dimension, followed by physical colocation and administrative hierarchy.
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| 22. |
- Broberg, Karin, et al.
(author)
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Evaluation of 92 cardiovascular proteins in dried blood spots collected under field-conditions : Off-the-shelf affinity-based multiplexed assays work well, allowing for simplified sample collection
- 2021
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In: BioEssays. - : Wiley. - 0265-9247 .- 1521-1878. ; 43:9
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Journal article (peer-reviewed)abstract
- Workplace-collected blood spots deposited on filter paper were analysed with multiplexed affinity-based protein assays and found to be suitable for proteomics analysis. The protein extension assay (PEA) was used to characterize 92 proteins using 1.2 mm punches in repeated samples collected from 20 workers. Overall, 97.8% of the samples and 91.3% of the analysed proteins passed quality control. Both within and between spot correlations using six replicates from the same individual were above 0.99, suggesting that comparable levels are obtained from multiple punches from the same spot and from consecutive spots. Protein levels from dried blood and wet serum from the same individuals were compared and the majority of the analysed proteins were found to be significantly correlated. These results open up for simplified sample collection of blood in field conditions for proteomic analysis, but also highlight that not all proteins can be robustly measured from dried whole blood.
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| 23. |
- Cadrin-Tourigny, Julia, et al.
(author)
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A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
- 2022
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 43:32, s. 1-9
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Journal article (peer-reviewed)abstract
- Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods and results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: Age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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| 24. |
- Cadrin-Tourigny, Julia, et al.
(author)
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Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy : A Multinational Collaboration
- 2021
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In: Circulation: Arrhythmia and Electrophysiology. - : Lippincott Williams & Wilkins. - 1941-3149 .- 1941-3084. ; 14:1
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Journal article (peer-reviewed)abstract
- Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.
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| 25. |
- Carlsson, Anna K, 1966, et al.
(author)
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Dynamic Responses of Female Volunteers in Rear Impact Sled Tests at Two Head Restraint Distances
- 2021
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In: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 9
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Journal article (peer-reviewed)abstract
- The objective of this study was to assess the biomechanical and kinematic responses of female volunteers with two different head restraint (HR) configurations when exposed to a low-speed rear loading environment. A series of rear impact sled tests comprising eight belted, near 50th percentile female volunteers, seated on a simplified laboratory seat, was performed with a mean sled acceleration of 2.1 g and a velocity change of 6.8 km/h. Each volunteer underwent two tests; the first test configuration, HR10, was performed at the initial HR distance ∼10 cm and the second test configuration, HR15, was performed at ∼15 cm. Time histories, peak values and their timing were derived from accelerometer data and video analysis, and response corridors were also generated. The results were separated into three different categories, HR10C (N = 8), HR15C (N = 6), and HR15NC (N= 2), based on: (1) the targeted initial HR distance [10 cm or 15 cm] and (2) whether the volunteers’ head had made contact with the HR [Contact (C) or No Contact (NC)] during the test event. The results in the three categories deviated significantly. The greatest differences were found for the average peak head angular displacements, ranging from 10° to 64°. Furthermore, the average neck injury criteria (NIC) value was 22% lower in HR10C (3.9 m2/s2), and 49% greater in HR15NC (7.4 m2/s2) in comparison to HR15C (5.0 m2/s2). This study supplies new data suitable for validation of mechanical or mathematical models of a 50th percentile female. A model of a 50th percentile female remains to be developed and is urgently required to complement the average male models to enhance equality in safety assessments. Hence, it is important that future protection systems are developed and evaluated with female properties taken into consideration too. It is likely that the HR15 test configuration is close to the limit for avoiding HR contact for this specific seat setup. Using both datasets (HR15C and HR15NC), each with its corresponding HR contact condition, will be possible in future dummy or model evaluation.
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