| 1. |
- Barros, Guilherme, 1992-
(author)
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Estimation of hazard ratios from observational data with applications related to stroke
- 2024
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Doctoral thesis (other academic/artistic)abstract
- The objective of this thesis is to examine some challenges that may emerge when conducting time-to-event studies based on observational data. Time-to-event (also called survival) is a setting that involves analyzing how different factors may influence the length of time until an individual experiences the event of interest. This type of analysis is commonly applied in fields such as medical research and epidemiology. In this thesis, which focuses on stroke, we are interested in the time to a recurrent stroke or the death of a patient who survived a first stroke.Hazard ratios are one of the main parameters estimated in time-to-event studies. Hazard ratios involve comparing the risk of experiencing the event between two groups, usually a treated group and an untreated group. They can also involve other factors, such as different age groups. Hazard ratios can be estimated from the data by using the Cox regression model.Observational data, in contrast to experimental data, involves data collected without any intervention or random assignment of treatment to the individuals. Confounders, that is, variables that distort or obscure the true relationship between treatment and outcome, are always present and need to be controlled for in observational studies.National registers are an important source of observational data. A national registry is a centralized database or system that collects, stores, and maintains information about a specific population or group of individuals within a country. Sweden is known for its detailed and complete national registers. In this thesis, data from the Swedish Stroke Register (Riksstroke) is used to study factors related to stroke.In time-to-event studies involving observational data, several challenges may arise for the researcher during data analysis. Some individuals may not experience the event during the observation period and thus the information about their time until the event is incomplete. These individuals are considered as censored. Some individuals may experience another event rather than the one of interest, a competing risk. Additionally, models must be properly constructed, with researchers selecting variables and determining the suitable functional form.Four papers are included in the thesis. Paper I demonstrates how to handle competing risks in survival analysis. The study involves comparing individuals with and without standard modifiable risk factors and their risks of a recurrent stroke or death using data from the Swedish Stroke Register.The estimation of marginal hazard ratios is a common theme in the other three papers. All involve simulation studies in order to extend methods and explore best practices when estimating marginal hazard ratios.Paper II explores non-parametric methods that can be used as alternatives to more traditional parametric methods when balancing datasets in order to estimate a marginal hazard ratio. A case study was also conducted using data from the Swedish Stroke Register involving the prescription of anticoagulants at hospital discharge after a stroke.Paper III is about how censoring affects marginal hazard ratio estimation, even with perfect balancing of the dataset. We study this issue, taking into consideration varying effect sizes and censoring rates. A procedure to attenuate the problem is also studied.Paper IV concerns covariate selection in the case of high-dimensional data. High-dimensional data involves cases in which the number of covariates in the study is comparable to the number of individuals, and therefore covariate selection methods are needed. In the paper, we explore some of these methods and suggest a best-performing procedure. As Paper II, Paper IV involves a case study of anticoagulant prescription using data from the Swedish Stroke Register.
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| 2. |
- Boström, Petrus, et al.
(author)
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Oncological Impact of High Vascular Tie After Surgery for Rectal Cancer : A Nationwide Cohort Study
- 2021
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In: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 274:3, s. e236-e244
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Journal article (peer-reviewed)abstract
- Objective: The purpose of this study was to investigate the impact of tie level on oncological outcomes in rectal cancer surgery.Summary background data: Theoretically, a high tie of the inferior mesenteric artery could facilitate removal of apical node metastases and improve tumor staging accuracy. However, no appropriately sized randomized controlled trial exists and results from observational studies are not consistent.Methods: All stage I–III rectal cancer patients who underwent abdominal surgery with curative intention in 2007 to 2014 were identified and followed, using the Swedish Colorectal Cancer Registry. Primary outcome was cancer-specific survival, whereas overall and relative survival, locoregional and distant recurrence, and lymph node harvest were secondary outcomes, with high tie as exposure. We used propensity score matching to emulate a randomized controlled trial, and then performed Cox regression analyses to estimate hazard ratios (HRs) with confidence intervals (CIs).Results: Some 8287 patients remained for analysis, of which 37% had high tie surgery. After propensity score matching, the 5-year cancer-specific survival rate was overall 86% and we found no association between the level of tie and cancer-specific (HR 0.92, 95% CI 0.79–1.07) or overall (HR 0.98, 95% CI 0.89–1.08) survival, nor to locoregional (HR 0.85, 95% CI 0.59–1.23) or distant (HR 1.01, 95% CI 0.88–1.15) recurrence, nor to relative survival (HR 1.05, 95% CI 0.85–1.28). Stratification and sensitivity analyses were similarly insignificant, after adjustment for confounding. Total lymph node harvest was, however, increased after high tie surgery (P < 0.01), but no differences were seen regarding positive nodes (P = 0.72).Conclusion: In this nationwide cohort study, the level of tie did not influence any patient-oriented oncological outcome, neither overall nor in node-positive patients. This would allow the patient's anatomical configuration and the surgeon's preferences to determine the level of tie.
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| 3. |
- Castro, Daniele Oliveira, et al.
(author)
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The use of a pilot-scale continuous paper process for fire retardant cellulose-kaolinite nanocomposites
- 2018
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In: Composites Science And Technology. - : Elsevier Ltd. - 0266-3538 .- 1879-1050. ; 162, s. 215-224
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Journal article (peer-reviewed)abstract
- Nanostructured materials are difficult to prepare rapidly and at large scale. Melt-processed polymer-clay nanocomposites are an exception, but the clay content is typically below 5 wt%. An approach for manufacturing of microfibrillated cellulose (MFC)/kaolinite nanocomposites is here demonstrated in pilot-scale by continuous production of hybrid nanopaper structures with thickness of around 100 μm. The colloidal nature of MFC suspensions disintegrated from chemical wood fiber pulp offers the possibility to add kaolinite clay platelet particles of nanoscale thickness. For initial lab scale optimization purposes, nanocomposite processing (dewatering, small particle retention etc) and characterization (mechanical properties, density etc) were investigated using a sheet former (Rapid Köthen). This was followed by a continuous fabrication of composite paper structures using a pilot-scale web former. Nanocomposite morphology was assessed by scanning electron microscopy (SEM). Mechanical properties were measured in uniaxial tension. The fire retardancy was evaluated by cone calorimetry. Inorganic hybrid composites with high content of in-plane oriented nanocellulose, nanoclay and wood fibers were successfully produced at pilot scale. Potential applications include fire retardant paperboard for semi structural applications and as reinforcement mats in molded thermoset biocomposites.
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| 4. |
- Cedervall, Johan, et al.
(author)
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Influence of cobalt substitution on the magnetic properties of Fe5PB2
- 2018
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In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 57:2, s. 777-784
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Journal article (peer-reviewed)abstract
- In this study the effects of cobalt substitutions in Fe5PB2 have been studied. An increased cobalt content reduces the magnetic exchange interactions. This has been concluded from a large, linear decrease in both the Curie temperature as well as the saturated magnetic moment. At high cobalt concentrations, cobalt prefers to order at the M(2) position in the crystal structure. A tunable Curie transition like this shows some prerequisites for magnetic cooling applications.The substitutional effects of cobalt in (Fe1–xCox)5PB2 have been studied with respect to crystalline structure and chemical order with X-ray diffraction and Mössbauer spectroscopy. The magnetic properties have been determined from magnetic measurements, and density functional theory calculations have been performed for the magnetic properties of both the end compounds, as well as the chemically disordered intermediate compounds. The crystal structure of (Fe1–xCox)5PB2 is tetragonal (space group I4/mcm) with two different metal sites, with a preference for cobalt atoms in the M(2) position (4c) at higher cobalt contents. The substitution also affects the magnetic properties with a decrease of the Curie temperature (TC) with increasing cobalt content, from 622 to 152 K for Fe5PB2 and (Fe0.3Co0.7)5PB2, respectively. Thus, the Curie temperature is dependent on composition, and it is possible to tune TC to a temperature near room temperature, which is one prerequisite for magnetic cooling materials.
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| 5. |
- Christakoudi, Sofia, et al.
(author)
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Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition
- 2020
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:10, s. 2680-2693
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Journal article (peer-reviewed)abstract
- Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.
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| 6. |
- Gardner, Chris J., et al.
(author)
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GH deficiency after traumatic brain injury : improvement in quality of life with GH therapy: analysis of the KIMS database
- 2015
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 172:4, s. 371-381
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Journal article (peer-reviewed)abstract
- Objective: Prevalence of GH deficiency (GHD) caused by traumatic brain injury (TBI) is highly variable. Short-term studies show improvement in quality of life (QoL) during GH replacement (GHR), but long-term data are lacking. The aim of this study was to analyse the clinical characteristics of post-traumatic hypopituitarism and the QoL effects of long-term GHR. Design/methods: Pfizer International Metabolic Database patients with GHD caused by TBI and by non-functioning pituitary adenoma (NFPA) were compared regarding: clinical characteristics at baseline and 1-year of GHR, and QoL response up to 8-years of GHR (QoL-AGHDA total scores and dimensions) in relationship with country-specific norms. Results: TBI patients compared with NFPA patients were younger, diagnosed with GHD 2.4 years later after primary disease onset (P<0.0001), had a higher incidence of isolated GHD, higher GH peak, a more favourable metabolic profile and worse QoL, were shorter by 0.9 cm (1.8 cm when corrected for age and gender; P=0.004) and received higher GH dose (mean difference: 0.04 mg/day P=0.006). In TBI patients, 1-year improvement in QoL was greater than in NFPA (change in QoL-AGHDA score 5.0 vs 3.5, respectively, P=0.04) and was sustained over 8 years. In TBI patients, socialisation normalised after 1 year of GHR, self-confidence and tenseness after 6 years and no normalisation of tiredness and memory was observed. Conclusion: Compared with NFPA, TBI patients presented biochemically with less severe hypopituitarism and worse QoL scores. GHR achieved clinically relevant, long-term benefit in QoL.
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| 7. |
- Häggström, Daniel, et al.
(author)
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A Verified and Validated Model for Simulation-Driven Design of Heavy Duty Truck Synchronizers
- 2015
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In: ASME Proceedings | ASME 2015 Power Transmission and Gearing Conference. - : ASME Press. - 9780791857205
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Conference paper (peer-reviewed)abstract
- The strong market trend toward lower fuel consumption for heavy road transports requires more frequent gear shifting and increased gear shift performance, i.e. shorter shift time. Increased shift performance means higher loads for the synchronizer which brings component and shifting process optimization more into focus.Traditionally, synchronizer development has relied on physical testing of complete synchronizers in general gearbox test rigs or in specialized synchronization test rigs leaving much of the causes of the observed effects unclear. This paper presents a generalized FE-based thermomechanical simulation model to be used for model-based synchronizer analysis and design. The model is targeted for studies of how different external loads and the values of different synchronizer design parameters affect the temperature transient in the friction lining. Recommendations of how major modeling complications should be treated are presented. The developed simulation model is verified and validated with a combination of analytical means and transient temperature measurements of bulk and surface temperatures. The applicability of the presented model, as well as its limitations, are discussed and exemplified with different design cases.
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| 8. |
- Häggström, Daniel, et al.
(author)
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Evaluation of synchronizer loading parameters and their ability to predict failure
- 2018
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In: Proceedings of the Institution of mechanical engineers. Part J, journal of engineering tribology. - : Sage Publications. - 1350-6501 .- 2041-305X. ; 232:9, s. 1093-1104
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Journal article (peer-reviewed)abstract
- Molybdenum coated gearbox synchronizers are tested in a mu-comp test rig under varying loading conditions until failure. Four different parameters used to describe the thermomechanical load are evaluated just before failure to compare their ability to predict failure. The parameters evaluated are the synchronized kinetic energy, the synchronization power, and the focal as well as the average surface temperature increase. The focal surface temperature increase as well as the average surface temperature increase is found to predict failure with relatively good accuracy. It is shown that there exists a threshold which divides the synchronizer into either a very long or a very short service life. Additionally, a method to determine the average surface temperature in the gearbox management system is proposed.
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| 9. |
- Häggström, Daniel
(author)
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On synchronization of heavy truck transmissions
- 2016
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Licentiate thesis (other academic/artistic)abstract
- Gear shifts are becoming more and more important as engines are adapted to low speed high torque working conditions. Synchronizers are key components for successful gear shifts. To adapt the synchronizers to new working conditions due to adaptations to new engines, improved development tools are needed. The presented thesis describes the development of two types of numerical models for the synchronization process, namely fluid-structure interaction to simulate the pre-synchronization phase and thermomechanical FE models to simulate the main synchronization phase. A methodology for developing friction models based on a combination of physical testing and numerical simulations is presented. Additionally, a comprehensive gear shift and synchronizer frame of reference section is presented.In paper A, two numerical fluid-structure interaction simulation models for assessing the pre-synchronization phase are presented. Simulations show that the synchronizer functionality is highly dependent on the gear shift maneuvering system, and that grooves in the synchronizer surface have a positive effect on the oil evacuation during the pre-synchronization phase.Paper B describes the development of a numerical thermomechanical model for simulating the main synchronization phase. Two parameter studies were performed, one based on external loads and one based on synchronizer geometry. The effect on the temperature increase from differences in thermal properties between molybdenum and carbon friction linings are presented.In paper C, a verification and validation methodology for highly transient thermomechanical processes was presented. Numerical verification, bulk temperature measurement, surface temperature measurement and qualitative visual inspection were combined to verify and validate the simulation model presented in paper B.In paper D, a methodology combining physical testing with an thermomechanical simulation model to develop a friction model was exemplified by a molybdenum coated synchronizer. A simplified thermal model was developed to remove the dependence of full finite element thermal models. The friction models shows good agreement with measured data.
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| 10. |
- Häggström, Daniel, et al.
(author)
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Optimization of synchronizer cone angle with regard to manufacturing tolerances of cone roundness and cone angle
- 2020
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In: Proceedings of the Institution of mechanical engineers. Part D, journal of automobile engineering. - : SAGE PUBLICATIONS LTD. - 0954-4070 .- 2041-2991. ; 234:2-3, s. 681-688
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Journal article (peer-reviewed)abstract
- The effects of manufacturing tolerances on the maximum focal temperature has been investigated by transient thermomechanical simulations. Both relative cone angle and cone out-of-roundness for molybdenum and carbon fibre reinforced polymer synchronizers were evaluated. It was shown that cone out-of-roundness significantly increases the focal contact temperature for that specific cone but has little impact on the opposing cone. Two populations of measured synchronizers were evaluated, and it was shown that the maximum focal surface temperature can be decreased in almost all tolerance cases by introducing a relative angle between the cones.
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