| 1. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 2. |
- Gustafsson, Anna, et al.
(författare)
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Subject-specific FE models of the human femur predict fracture path and bone strength under single-leg-stance loading
- 2021
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 113
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Tidskriftsartikel (refereegranskat)abstract
- Hip fractures are a major health problem with high socio-economic costs. Subject-specific finite element (FE) models have been suggested to improve the fracture risk assessment, as compared to clinical tools based on areal bone mineral density, by adding an estimate of bone strength. Typically, such FE models are limited to estimate bone strength and possibly the fracture onset, but do not model the fracture process itself. The aim of this study was to use a discrete damage approach to simulate the full fracture process in subject-specific femur models under stance loading conditions. A framework based on the partition of unity finite element method (PUFEM), also known as XFEM, was used. An existing PUFEM framework previously used on a homogeneous generic femur model was extended to include a heterogeneous material description together with a strain-based criterion for crack initiation. The model was tested on two femurs, previously mechanically tested in vitro. Our results illustrate the importance of implementing a subject-specific material distribution to capture the experimental fracture pattern under stance loading. Our models accurately predicted the fracture pattern and bone strength (1% and 5% error) in both investigated femurs. This is the first study to simulate complete fracture paths in subject-specific FE femur models and it demonstrated how discrete damage models can provide a more complete picture of fracture risk by considering both bone strength and fracture toughness in a subject-specific fashion.
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| 3. |
- Harbst, Katja, et al.
(författare)
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Multiregion whole-exome sequencing uncovers the genetic evolution and mutational heterogeneity of early-stage metastatic melanoma
- 2016
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Ingår i: Cancer Research. - 0008-5472. ; 76:16, s. 4765-4774
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Tidskriftsartikel (refereegranskat)abstract
- Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma biopsies from eight individual tumors. This approach revealed heterogeneous somatic mutations in the range of 3%-38% in individual tumors. Known mutations in melanoma drivers BRAF and NRAS were always ubiquitous events. Using RNA sequencing, we found that the majority of mutations were not expressed or were expressed at very low levels, and preferential expression of a particular mutated allele did not occur frequently. In addition, we found that the proportion of ultraviolet B (UVB) radiation-induced C>T transitions differed significantly (P <0.001) between early and late mutation acquisition, suggesting that different mutational processes operate during the evolution of metastatic melanoma. Finally, clinical history reports revealed that patients harboring a high degree of mutational heterogeneity were associated with more aggressive disease progression. In conclusion, our multiregion tumor-sequencing approach highlights the genetic evolution and non-UVB mutational signatures associated with melanoma development and progression, and may provide a more comprehensive perspective of patient outcome.
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| 4. |
- Heikkilä, Mia, et al.
(författare)
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Differentiations in visibility - male advantages and female disadvantages in gender-segregated programmes
- 2020
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Ingår i: Frontiers in Sociology. - Lausanne : Frontiers Media S.A.. - 2297-7775. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- This article stresses the importance of understanding that women and men in gender-segregated programmes experience their gender minority positions very differently. It stems from an interest in the kind of interventions that academia should address in order to reduce gender segregation and provide women and men with the same educational opportunities and personal development. In relation to the obvious and continuing gender differences along a horizontal dimension, previous research seems to have had a limited impact in breaking gender stereotypes and promoting women and men to more atypical fields. The empirical data consists of 25 semi-structured, individual interviews from underrepresented students' gender-related experiences/thoughts about their programmes. By using the concepts of “visibility,” “sense of belonging,” and “negotiating otherness” to analyze how negotiation and belonging are part of students' everyday university lives this study's most important contributions are its findings regarding the differentiations in visibility. A continuum of visibility experiences is explored, from men who receive positive attention to women who are being considered as less knowledgeable. Our visibility scale indicates, as does previous research, that there are differences between how female and male students become visible, but the differences can also appear within both groups of students. This knowledge is crucial when designing interventions so as to provide positive study environments for both women and men. Also—in a broader perspective—it is important in order to recruit and ensure that gender minority students remain in the programs. © 2020 Heikkilä, Isaksson and Stranne.
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| 5. |
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| 6. |
- Isaksson, Frida, et al.
(författare)
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Evaluating the Use of Alternative Normalization Approaches on SARS-CoV-2 Concentrations in Wastewater: Experiences from Two Catchments in Northern Sweden
- 2022
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Ingår i: Environments. - : MDPI. - 2076-3298. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- The detection of SARS-CoV-2 RNA fragments in feces has paved the way for wastewater-based epidemiology to contribute to COVID-19 mitigation measures, with its use in a public health context still under development. As a way to facilitate data comparison, this paper explores the impact of using alternative normalization approaches (wastewater treatment plant (WWTP) flow, population size estimates (derived using total nitrogen (TN), total phosphorus (TP) and census data) and pepper mild mottle virus (PMMoV)) on the relationship between viral wastewater data and clinical case numbers. Influent wastewater samples were collected at two WWTPs in Luleå, northern Sweden, between January and March 2021. TN and TP were determined upon sample collection, with RNA analysis undertaken on samples after one freeze–thaw cycle. The strength of the correlation between normalization approaches and clinical cases differed between WWTPs (r ≤ 0.73 or r ≥ 0.78 at the larger WWTP and r ≤ 0.23 or r ≥ 0.43 at the smaller WWTP), indicating that the use of wastewater as an epidemiological tool is context-dependent. Depending on the normalization approach utilized, time-shifted analyses imply that wastewater data on SARS-CoV-2 RNA pre-dated a rise in clinical cases by 0–2 and 5–8 days, for the lager and smaller WWTPs, respectively. SARS-CoV-2 viral loads normalized to the population or PMMoV better reflect the number of clinical cases when comparing wastewater data between sewer catchments.
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| 7. |
- Isaksson, Frida, et al.
(författare)
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Greywater reuse for different purposes in Sweden : A literature review
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Globally, water demands are increasing as a result of e.g., population growth and a warmer climate; at the same time freshwater supplies are becoming scarcer. Also in parts of Sweden where water shortage historically has not been a concern, the availability of freshwater for potable water use is declining, especially in the summer. As a result, alternative water management strategies are receiving increased attention in an effort to reduce the pressure on potable water sources. One strategy is the treatment, recirculation and re-use of greywater, a type of water that can be collected in source-separating wastewater systems. Hence, the aim of this literature review was to provide knowledge necessary to understand how greywater can be treated, recycled and re-used in the society, with an emphasis on reuse in Sweden. The review covers different aspects including greywater characteristics, greywater treatment processes, legal frameworks and guidelines on greywater re-use, global examples as well as summary of findings from sustainability analyses conducted on greywater re-use systems.Greywater makes up 75–90% of the total domestic wastewater volume and thereby represents an important source for water reuse in systems with source-separating wastewater systems. Data of the quantity of greywater produced in households globally and in Sweden vary. According to Swedish studies, one person may produce between 66 to 150 l/d. Additionally, research indicates that greywater contains less pathogens and nutrients compared to mix wastewater due to the separation of greywater from blackwater, which in turn contains the human excreta. However, the concentrations of measured parameters vary significantly between different areas. Therefore, in order to ensure the quality of greywater, site-specific measures are necessary.Studies have been conducted on different greywater treatment methods for non-potable re-use, with biological and filtration techniques receiving the most attention. However, it is challenging to make generalizations about the optimal treatment techniques based on the end-usage, due to the variation in greywater characteristics between sites. In addition, this review shows that there is a lack of legal guidance for greywater reuse, which makes it more challenging for practitioners to understand what levels of treatment that are required before the reclaimed water can be reused in used in society. The review also shows that further sustainability analyses should be conducted on greywater reuse systems, in order to understand their benefits more comprehensively.
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| 8. |
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| 9. |
- Sanna, Adriana, et al.
(författare)
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DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype
- 2022
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 7:19
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Tidskriftsartikel (refereegranskat)abstract
- Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, MITF and SOX10, important in melanoma development and progression have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF methylated cultures were subdivided in two distinct subtypes. Examining mRNA levels of neural crest associated genes we found that one subtype had lost the expression of several lineage genes including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF methylated melanoma cells using CRISPR/Cas9 confirmed these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
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| 10. |
- Sanna, Adriana, et al.
(författare)
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DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype.
- 2022
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Ingår i: JCI insight. - : The American Society for Clinical Investigation. - 2379-3708. ; 7:19
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Tidskriftsartikel (refereegranskat)abstract
- Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug-tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte-specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, microphthalmia-associated transcription factor (MITF) and SRY-box transcription factor 10 (SOX10), important in melanoma development and progression, have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation, and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF-methylated cultures were subdivided in 2 distinct subtypes. Examining mRNA levels of neural crest-associated genes, we found that 1 subtype had lost the expression of several lineage genes, including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF-methylated melanoma cells using CRISPR/Cas9 supported these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
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