| 1. |
|
|
| 2. |
- Simonsson, Christian, et al.
(author)
-
A unified framework for prediction of liver steatosis dynamics in response to different diet and drug interventions
- 2024
-
In: Clinical Nutrition. - : CHURCHILL LIVINGSTONE. - 0261-5614 .- 1532-1983. ; 43:6, s. 1532-1543
-
Journal article (peer-reviewed)abstract
- Background & aims: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder, characterized by the accumulation of excess fat in the liver, and is a driving factor for various severe liver diseases. These multi -factorial and multi-timescale changes are observed in different clinical studies, but these studies have not been integrated into a uni fied framework. In this study, we aim to present such a uni fied framework in the form of a dynamic mathematical model. Methods: For model training and validation, we collected data for dietary or drug -induced interventions aimed at reducing or increasing liver fat. The model was formulated using ordinary differential equations (ODEs) and the mathematical analysis, model simulation, model formulation and the model parameter estimation were all performed in MATLAB. Results: Our mathematical model describes accumulation of fat in the liver and predicts changes in lipid fluxes induced by both dietary and drug interventions. The model is validated using data from a wide range of drug and dietary intervention studies and can predict both short-term (days) and long-term (weeks) changes in liver fat. Importantly, the model computes the contribution of each individual lipid flux to the total liver fat dynamics. Furthermore, the model can be combined with an established bodyweight model, to simulate even longer scenarios (years), also including the effects of insulin resistance and body weight. To help prepare for corresponding eHealth applications, we also present a way to visualize the simulated changes, using dynamically changing lipid droplets, seen in images of liver biopsies. Conclusion: In conclusion, we believe that the minimal model presented herein might be a useful tool for future applications, and to further integrate and understand data regarding changes in dietary and drug induced changes in ectopic TAG in the liver. With further development and validation, the minimal model could be used as a disease progression model for steatosis. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
|
| 3. |
- Dömstedt, Peter, et al.
(author)
-
Corrosion studies of a low alloyed Fe-10Cr-4Al steel exposed in liquid Pb at very high temperatures
- 2020
-
In: Journal of Nuclear Materials. - : ELSEVIER. - 0022-3115 .- 1873-4820. ; 531
-
Journal article (peer-reviewed)abstract
- The aim of the work has been to study the corrosion resistance of a new low alloyed experimental FeCrAl steel, with the potential use as corrosion barrier in high temperature lead based energy applications. The exposures were conducted in liquid lead at 800 degrees C and 900 degrees C, with controlled oxygen environment, for up to 1760 h. The results demonstrate that the new experimental alloy had formed a protective oxide in both exposures, with no indications of lead penetration. The alloy showed better corrosion properties than that of the reference materials: Kanthal APMT, Kanthal APMTT and AISI 316L. This indicates that the ductile Fe-10Cr-4Al-RE steel can be used as a corrosion barrier in liquid lead based clean energy applications, operating at very high temperatures.
|
|
| 4. |
- Dömstedt, Peter
(author)
-
Development of Alumina Forming Alloys for High-Temperature Energy Applications
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Liquid lead as heat transfer fluid presents attractive features for future power technologies, such as next-generation nuclear reactors, thermal solar power, and thermal storage. Liquid lead has excellent heat transfer properties well suited for operating at high temperatures. While today's water-cooled reactors operate at a temperature of approximately 300°C, the next-generation lead-cooled nuclear power could operate up to 600°C, significantly increasing the energy conversion efficiency. However, it is well known that liquid lead is a corrosive medium for stainless steels, especially at temperatures above 500°C.To address the corrosion issues, aluminium oxide-forming ferritic steels have been thoroughly studied in liquid lead environments and have shown good oxidation properties. Traditionally, these steels are alloyed with 3-6 wt% aluminium and 12-24 wt% chromium, and iron as balance, hence the denotation FeCrAl steel. However, the high addition of aluminium and chromium results in poor weldability and renders them susceptible to embrittlement in the desired temperature range. Therefore, to address the welding and embrittlement issues, a new group of FeCrAl materials was developed in recent years with only 10 wt% chromium and 4 wt% aluminium, which in this work is referred to as Fe-10Cr-4Al. These alloys have shown good ductility and good corrosion properties in liquid lead up to 550°C.In this work, the Fe-10Cr-4Al steels have been further optimised and exposed to liquid lead at temperatures up to 900°C. In addition, detailed studies of the oxidation properties and structure formed on the steel surfaces were conducted using various analytical techniques. The findings showed that the most promising Fe-10Cr-4Al steel, so far, has suitable corrosion properties up to 800°C. However, although these steels have improved mechanical and welding properties, they do not meet the requirements set for the desired high-temperature energy applications.Therefore, another new family of alloys was developed, namely alumina-forming martensitic steels. This development aimed to combine the superior corrosion resistance of the aluminium oxide with the mechanical properties inherent in the martensitic structure. The development was done using thermodynamic modelling, empirical corrosion studies and detailed analytical methods. The results showed that these martensitic steels have a corrosion resistance exceeding even the best1optimised Fe-10Cr4-Al steel in liquid lead at temperatures up to at least 550°C.In parallel, alumina-forming austenitic steels were also developed. The aim was to find a suitable composition for these materials that not only provide good corrosion protection in liquid lead, but also good weldability, good phase stability, and good formability. These austenitic materials have shown, in general, good corrosion properties in liquid lead up to 600°C. However, the combination of elevated Ni, Al and Mn levels resulted in embrittlement after ageing at 600°C. In addition, a series of austenitic alumina-forming welding materials were also developed within this work. The aim was to produce a material that does not suffer from the embrittlement commonly observed in ferritic welds. Bend testing of this welding material has, so far, indicated ductile behaviour with good formability.
|
|
| 5. |
- Herrgårdh, Tilda, et al.
(author)
-
A multi-scale digital twin for adiposity-driven insulin resistance in humans : diet and drug effects
- 2023
-
In: Diabetology & Metabolic Syndrome. - : BioMed Central (BMC). - 1758-5996. ; 15:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The increased prevalence of insulin resistance is one of the major health risks in society today. Insulin resistance involves both short-term dynamics, such as altered meal responses, and long-term dynamics, such as the development of type 2 diabetes. Insulin resistance also occurs on different physiological levels, ranging from disease phenotypes to organ-organ communication and intracellular signaling. To better understand the progression of insulin resistance, an analysis method is needed that can combine different timescales and physiological levels. One such method is digital twins, consisting of combined mechanistic mathematical models. We have previously developed a model for short-term glucose homeostasis and intracellular insulin signaling, and there exist long-term weight regulation models. Herein, we combine these models into a first interconnected digital twin for the progression of insulin resistance in humans.METHODS: The model is based on ordinary differential equations representing biochemical and physiological processes, in which unknown parameters were fitted to data using a MATLAB toolbox. RESULTS: The interconnected twin correctly predicts independent data from a weight increase study, both for weight-changes, fasting plasma insulin and glucose levels, and intracellular insulin signaling. Similarly, the model can predict independent weight-change data in a weight loss study with the weight loss drug topiramate. The model can also predict non-measured variables.CONCLUSIONS: The model presented herein constitutes the basis for a new digital twin technology, which in the future could be used to aid medical pedagogy and increase motivation and compliance and thus aid in the prevention and treatment of insulin resistance.
|
|
| 6. |
- Lundberg, Mathias, et al.
(author)
-
Challenges and opportunities in the diagnosis and treatment of early-onset psychosis : a case series from the youth affective disorders clinic in Stockholm, Sweden
- 2024
-
In: Schizophrenia. - : Springer Nature. - 2754-6993. ; 10:1
-
Journal article (peer-reviewed)abstract
- Early-onset psychosis is linked to adverse long-term outcomes, recurrent disease course, and prolonged periods of untreated illness; thus highlighting the urgency of improving early identification and intervention. This paper discusses three cases where initial emphasis on psychosocial treatments led to diagnostic and therapeutic delays: (1) a 15-year-old misdiagnosed with emotionally unstable personality disorder and autism, who improved on bipolar medication and antipsychotics; (2) another 15-year-old misdiagnosed with autism, who stabilized on lithium and antipsychotics, subsequently allowing for gender dysphoria evaluation; (3) a 9-year-old autistic boy incorrectly treated for ADHD, who recovered with appropriate antipsychotic treatment. These cases illuminate the vital importance of adhering to a diagnostic hierarchy, prioritizing diagnostic utility, and conducting longitudinal evaluations to facilitate early targeted treatment of psychotic symptoms in early-onset psychosis. Adherence to such strategies can minimize delays in managing early-onset psychosis and improve long-term prognoses.
|
|
| 7. |
- Silfvergren, Oscar, et al.
(author)
-
Digital twin predicting diet response before and after long-term fasting
- 2022
-
In: PloS Computational Biology. - : Public Library of Science. - 1553-734X .- 1553-7358. ; 18:9
-
Journal article (peer-reviewed)abstract
- Today, there is great interest in diets proposing new combinations of macronutrient compositions and fasting schedules. Unfortunately, there is little consensus regarding the impact of these different diets, since available studies measure different sets of variables in different populations, thus only providing partial, non-connected insights. We lack an approach for integrating all such partial insights into a useful and interconnected big picture. Herein, we present such an integrating tool. The tool uses a novel mathematical model that describes mechanisms regulating diet response and fasting metabolic fluxes, both for organ-organ crosstalk, and inside the liver. The tool can mechanistically explain and integrate data from several clinical studies, and correctly predict new independent data, including data from a new study. Using this model, we can predict non-measured variables, e.g. hepatic glycogen and gluconeogenesis, in response to fasting and different diets. Furthermore, we exemplify how such metabolic responses can be successfully adapted to a specific individuals sex, weight, height, as well as to the individuals historical data on metabolite dynamics. This tool enables an offline digital twin technology.
|
|
| 8. |
- Simonsson, Christian, 1992-
(author)
-
Mathematical Modelling of MASLD ‐ Towards Digital Twins in Liver Disease
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- Unhealthy dieting and a sedentary lifestyle are causing an increased prevalence of obesity related complications. One such complication is metabolic dysfunction-associated steatotic liver disease (MASLD) the manifestation of metabolic dysregulation and insulin resistance in the liver. Today, MASLD effect a third of the world’s population. One of the main characteristics of MASLD is accumulation of ectopic lipids in the liver, also denoted steatosis. Steatosis is not inherently dangerous but is an indication of metabolic dysregulation, and long-term MASLD can progress into severe conditions such as chronic hepatic inflammation denoted metabolic dysfunction-associated steatohepatitis (MASH), liver scarring (cirrhosis), and primary liver cancer (hepatocellular carcinoma, HCC). Moreover, these conditions can be further aggravated by alcohol consumption. The increase in potential patients with MASLD will have an enormous burden on future healthcare. Thus, future healthcare has a need for innovative solutions to lessen this burden. Such solutions should be capable of personalized and preventive measures, cost-effective high throughput screening methods, and frameworks integrating all available patient data, for all stages of MASLD. Today, some of these methodologies already exist, however there is still a need for ways to integrate different liver biomarkers into a user-friendly framework, with strong personalization and predictive capabilities. For this purpose, data-driven mathematical modelling is of use. Data-driven mathematical models has proven useful for such integration in other disease areas such as stroke. In this thesis, I have created and explored several mathematical models aimed at exploring different aspects of MASLD, as well as developed several models using data from example: our own collected magnetic resonance imaging (MRI) data from patients suffering from chronic liver disease or HCC, and pre-clinical mouse data of insulin resistance progression. The studies presented in this thesis investigate diet-driven insulin resistance development, steatosis development and screening, as well as lifestyle interventions for alcohol and dietary habits, and liver function evaluation at late-stage liver disease. Thus, this thesis presents a possible fundament to create a so-called digital twin of MASLD – a highly personalized model capable of making predictions based on lifestyle.
|
|
| 9. |
- Tapper, Sofie, 1989-, et al.
(author)
-
A pilot study of essential tremor: cerebellar GABA+/Glx ratio is correlated with tremor severity
- 2020
-
In: Cerebellum & ataxias. - : BioMed Central. - 2053-8871. ; 7
-
Journal article (peer-reviewed)abstract
- Essential tremor is a common movement disorder with an unclear origin. Emerging evidence suggests the role of the cerebellum and the thalamus in tremor pathophysiology. We examined the two main neurotransmitters acting inhibitory (GABA+) and excitatory (Glx) respectively, in the thalamus and cerebellum, in patients diagnosed with severe essential tremor. Furthermore, we also investigated the relationship between determined neurotransmitter concentrations and tremor severity in the essential tremor patients.
|
|
| 10. |
|
|
