| 1. |
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| 2. |
- Aqvist, Johan, et al.
(författare)
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Bridging the gap between ribosome structure and biochemistry by mechanistic computations
- 2012
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Ingår i: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 22:6, s. 815-823
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Tidskriftsartikel (refereegranskat)abstract
- The wealth of structural and biochemical data now available for protein synthesis on the ribosome presents major new challenges for computational biochemistry. Apart from technical difficulties in modeling ribosome systems, the complexity of the overall translation cycle with a multitude of different kinetic steps presents a formidable problem for computational efforts where we have only seen the beginning. However, a range of methodologies including molecular dynamics simulations, free energy calculations, molecular docking and quantum chemical approaches have already been put to work with promising results. In particular, the combined efforts of structural biology, biochemistry, kinetics and computational modeling can lead towards a quantitative structure-based description of translation.
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| 3. |
- Herrmann, Björn, et al.
(författare)
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Comparison of a duplex quantitative real-time PCR assay and the COBAS Amplicor CMV Monitor test for detection of cytomegalovirus
- 2004
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 42:5, s. 1909-14
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Tidskriftsartikel (refereegranskat)abstract
- A duplex quantitative real-time PCR (qPCR) assay was designed to detect both the polymerase gene (pol) and the glycoprotein gene (gB) of cytomegalovirus (CMV). The detection limit of the qPCR was determined to be 1 to 3 copies/reaction and the linear measure interval was 10(3) to 10(8) copies/ml. The qPCR system was compared to the COBAS Amplicor CMV Monitor test (COBAS) by an analysis of 138 plasma samples. Both systems detected CMV in 71 cases and had negative results for 33 samples. In addition, 34 samples were positive by qPCR and negative by the COBAS assay, but in no case was the COBAS result positive and the qPCR result negative. Thus, qPCR detected 48% more positive cases than the COBAS method. For samples with > or = 10(5) copies/ml by qPCR, a saturation effect was seen in the COBAS assay and quantification required dilution. Copy numbers for pol and gB by qPCR generally agreed. However, the reproducibility of qPCR assays and the need for an international standard are discussed. Discrepant copy numbers for pol and gB by qPCR were found for samples from two patients, and sequence analysis revealed that the corresponding CMV strains were mismatched at four nucleotide positions compared with the gB fragment primer sequences. In conclusion, a duplex qPCR assay in a real-time format facilitates quantitative measurements and minimizes the risk of false-negative results.
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| 4. |
- Lind, Christoffer, et al.
(författare)
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Codon-reading specificities of mitochondrial release factors and translation termination at non-standard stop codons
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- A key feature of mitochondrial translation is the reduced number of transfer RNAs and reassignment of codons. For human mitochondria, a major unresolved problem is how the set of stop codons are decoded by the release factors mtRF1a and mtRF1. Here we present three-dimensional structural models of human mtRF1a and mtRF1 based on their homology to bacterial RF1 in the codon recognition domain, and the strong conservation between mitochondrial and bacterial ribosomal RNA in the decoding region. Sequence changes in the less homologous mtRF1 appear to be correlated with specific features of the mitochondrial rRNA. Extensive computer simulations of the complexes with the ribosomal decoding site show that both mitochondrial factors have similar specificities and that neither reads the putative vertebrate stop codons AGA and AGG. Instead, we present a structural model for a mechanism by which the ICT1 protein causes termination by sensing the presence of these codons in the A-site of stalled ribosomes.
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| 5. |
- Mishra, Sushil Kumar, et al.
(författare)
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Computational prediction of monosaccharide binding free energies to lectins with linear interaction energy models
- 2012
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Ingår i: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 33:29, s. 2340-2350
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Tidskriftsartikel (refereegranskat)abstract
- The linear interaction energy (LIE) method to compute binding free energies is applied to lectin-monosaccharide complexes. Here, we calculate the binding free energies of monosaccharides to the Ralstonia solanacearum lectin (RSL) and the Pseudomonas aeruginosa lectin-II (PA-IIL). The standard LIE model performs very well for RSL, whereas the PA-IIL system, where ligand binding involves two calcium ions, presents a major challenge. To overcome this, we explore a new variant of the LIE model, where ligandmetal ion interactions are scaled separately. This model also predicts the saccharide binding preference of PA-IIL on mutation of the receptor, which may be useful for protein engineering of lectins.
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| 6. |
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| 7. |
- Satpati, Priyadarshi, et al.
(författare)
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Structure-Based Energetics of mRNA Decoding on the Ribosome
- 2014
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 53:10, s. 1714-1722
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Tidskriftsartikel (refereegranskat)abstract
- The origin of high fidelity in bacterial protein synthesis on the ribosome remains a fundamental unsolved problem despite available three-dimensional structures of different stages of the translation process. However, these structures open up the possibility of directly computing the energetics of tRNA selection that is required for an authentic understanding of fidelity in decoding. Here, we report extensive computer simulations that allow us to quantitatively calculate tRNA discrimination and uncover the energetics underlying accuracy in code translation. We show that the tRNA-mRNA interaction energetics varies drastically along the path from initial selection to peptide bond formation. While the selection process is obviously controlled by kinetics, the underlying thermodynamics explains the origin of the high degree of accuracy. The existence of both low- and high-selectivity states provides an efficient mechanism for initial selection and proofreading that does not require codon-dependent long-range structural signaling within the ribosome. It is instead the distinctly unequal population of the high-selectivity states for cognate and noncognate substrates that is the key discriminatory factor. The simulations reveal the essential roles played both by the 30S subunit conformational switch and by the common tRNA modification at position 37 in amplifying the accuracy.
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| 8. |
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| 9. |
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| 10. |
- Sund, Johan, et al.
(författare)
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Binding Site Preorganization and Ligand Discrimination in the Purine Riboswitch
- 2015
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 119:3, s. 773-782
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Tidskriftsartikel (refereegranskat)abstract
- The progress of RNA research has suggested a wide variety of RNA molecules as possible targets for pharmaceutical drug molecules. Structure-based computational methods for predicting binding modes and affinities are now important tools in drug discovery, but these methods have mainly been focused on protein targets. Here we employ molecular dynamics free-energy perturbation calculations and the linear interaction energy method to analyze the energetics of ligand binding to purine riboswitches. Calculations are carried out for 14 different purine complexes with the guanine and adenine riboswitches in order to examine their ligand recognition principles. The simulations yield binding affinities in good agreement with experimental data and rationalize the selectivity of the riboswitches for different ligands. In particular, it is found that these receptors have an unusually high degree of electrostatic preorganization for their cognate ligands, and this effect is further quantified by explicit free-energy calculations, which show that the standard electrostatic linear interaction energy parametrization is suboptimal in this case. The adenine riboswitch specifically uses the electrostatic preorganization to discriminate against guanine by preventing the formation of a G-U wobble base pair.
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| 11. |
- Sund, Johan, 1980-
(författare)
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From Structure to Function with Binding Free Energy Calculations for Codon Reading, Riboswitches and Lectins
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Molecular association is part of many important processes in living cells. Computational methods for calculating binding free energies allows for a quantitative examination of biomolecular structures and hypotheses drawn from biochemical experiments. Here, binding free energy calculations for tRNAs and release factors binding to mRNA codons on the ribosome, sugars binding to lectins and purine analogs binding to the purine riboswitch are presented.The relative affinities between cognate and non-cognate tRNAs for different states involved in codon reading on the ribosome were determined. The calculations show that tRNA discrimination varies between different conformations of the 30S subunit, where the existence of both low and high selectivity states provides an efficient common mechanism for initial selection and proofreading. The simulations reveal a desolvation mechanism for the 30S conformational switch with which the accuracy of peptide bond formation can be amplified.When an mRNA stop codon (UAA, UAG or UGA) is located in the ribosomal A-site release factors bind to the ribosome and the synthesized protein is released. RF1 is specific for UAA and UAG whereas RF2 is specific for UAA and UGA. The free energy calculations and an analysis of the performed simulations show the mechanisms for how RF1 and RF2 are able to read the stop codons with different specificities. Also mitochondrial release factors were investigated. Vertebrate mitochondria have four stop codons, UAA, UAG, AGA and AGG and two release factors mtRF1 and mtRF1a. The calculations show how the specificities of both mtRF1 and mtRF1a agree with RF1 and that none of them are likely to read the non-standard stop codons AGA and AGG.The linear interaction energy method has also been examined for the RSL and PA-IIL lectins and for the purine riboswitch. The standard parameterization of the method works well for RSL, but fails for PA-IIL and the purine riboswitch due to compositions of the active sites in these systems. The development of new parameterizations to overcome these problems leads to a better understanding of both the method and the binding mechanisms in these systems.
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| 12. |
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| 13. |
- Sund, Johan, et al.
(författare)
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Principles of stop-codon reading on the ribosome
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 465:7300, s. 947-U12
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Tidskriftsartikel (refereegranskat)abstract
- In termination of protein synthesis, the bacterial release factors RF1 and RF2 bind to the ribosome through specific recognition of messenger RNA stop codons and trigger hydrolysis of the bond between the nascent polypeptide and the transfer RNA at the peptidyl-tRNA site, thereby releasing the newly synthesized protein. The release factors are highly specific for a U in the first stop-codon position 1 and recognize different combinations of purines in the second and third positions, with RF1 reading UAA and UAG and RF2 reading UAA and UGA. With recently determined crystal structures of termination complexes(2-4), it has become possible to decipher the energetics of stop-codon reading by computational analysis and to clarify the origin of the high release-factor binding accuracy. Here we report molecular dynamics free-energy calculations on different cognate and non-cognate termination complexes. The simulations quantitatively explain the basic principles of decoding in all three codon positions and reveal the key elements responsible for specificity of the release factors. The overall reading mechanism involves hitherto unidentified interactions and recognition switches that cannot be described in terms of a tripeptide anticodon model. Further simulations of complexes with tRNA(Trp), the tRNA recognizing the triplet codon for Trp, explain the observation of a 'leaky' stop codon 5 and highlight the fundamentally different third position reading by RF2, which leads to a high stop-codon specificity with strong discrimination against the Trp codon. The simulations clearly illustrate the versatility of codon reading by protein, which goes far beyond tRNA mimicry.
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| 14. |
- Agudo, Antonio, et al.
(författare)
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Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 34:6, s. 1244-1250
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.
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| 15. |
- Andersson, Magnus N., et al.
(författare)
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Prophylactic mastectomy – Correlation between skin flap thickness and residual glandular tissue evaluated postoperatively by imaging
- 2022
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Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier. - 1748-6815 .- 1878-0539. ; 75:6, s. 1813-1819
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women with an increased hereditary risk of breast cancer can undergo risk-reducing prophylactic mastectomy. However, there is a balance between how much subcutaneous tissue should be resected to achieve maximal reduction of glandular tissue, while leaving viable skin flaps.Methods: Forty-five women previously operated with prophylactic mastectomy underwent magnetic resonance tomography (MRT) and ultrasound (US) to investigate the correlation between skin flap thickness and residual glandular tissue. Residual glandular tissue was documented as being present or not present, but not quantified, as the amount of residual glandular tissue in many cases was considered too small to make reliable volume quantifications with available tools. Since a mastectomy skin flap thickness of 5 mm is discussed as an oncologically safe thickness in the literature, this was used as a cut-off.Results: Following prophylactic mastectomy, residual glandular tissue was detected in 39.3% of all breasts and 27.9% of all the breast quadrants examined by MRT, and 44.1% of all breasts and 21.7% of all the breast quadrants examined by US. Residual glandular tissue was detected in 6.9% of the quadrants in skin flaps ≤ 5 mm and in 37.5% of the quadrants in skin flaps > 5 mm (OR 3.07; CI = 1.41–6.67; p = 0.005). Furthermore, residual glandular tissue increased significantly already when the skin flap thickness exceeded 7 mm.Conclusions: This study highlights that complete removal of glandular breast tissue during a mastectomy is difficult and suggests that this is an unattainable goal. We demonstrate that residual glandular tissue is significantly higher in skin flaps > 5 mm in comparison to skin flaps ≤ 5 mm, and that residual glandular tissue increases significantly already when the flap thickness exceeds 7 mm.
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| 16. |
- Appelgren, M., et al.
(författare)
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Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial
- 2022
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Ingår i: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 63, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQC30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.
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| 17. |
- Eriksson, Johan, et al.
(författare)
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Productivity in relation to organization of a surgical department : a retrospective observational study
- 2022
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Ingår i: BMC Surgery. - : BioMed Central (BMC). - 1471-2482. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Responsible and efficient resource utilization are important factors in healthcare. The aim of this study was to investigate how total case time differs between two differently organized surgical departments. Methods: This is a retrospective observational study of a cohort of patients undergoing elective surgery for breast cancer or malignant melanoma in a university hospital setting in Sweden. All patients were operated on by the same set of surgeons but in two different surgical departments: a general surgery (GS) and a cardiothoracic (CT) surgery department. Patients were selected to the two departments from a waiting list in the order of referral for surgery. The effect of being operated on at the CT department compared to the GS department was estimated by linear regression. Results: The final study cohort comprised 349 patients in the GS department and 177 patients in the CT department. Both groups were similar regarding surgical procedures, American Society of Anesthesiologists' score, body mass index, age, sex, and the skill level of the operating surgeon. These covariates were included in the linear regression model. The total case time, defined by the Procedural Time Glossary as room set-up start to room clean-up finish, was significantly shorter for the patients who underwent a surgical procedure at the CT department compared to the GS department, even after adjusting for the background characteristics of the patients and surgeon. After adjusting for the selected covariates, the average difference in total case time between the two departments was − 30.67 min (p = 0.001). Conclusions: A significantly shorter total case time was measured for operations in the CT department. Plausible explanations may be more beneficial organizational factors, such as staffing ratio, skill mix in the operating room team, and working behavioral aspects regarding resource utilization.
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| 18. |
- Fedirko, V., et al.
(författare)
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Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study
- 2014
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 60:4, s. 1222-1230
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Tidskriftsartikel (refereegranskat)abstract
- The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. © 2014 by the American Association for the Study of Liver Diseases.
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| 19. |
- Gari, Hala, et al.
(författare)
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Amperometric In Vitro Monitoring of Penetration through Skin Membrane
- 2015
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Ingår i: Electroanalysis. - : Wiley. - 1040-0397 .- 1521-4109. ; 27:1, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to demonstrate that penetration of quercetin, hydrogen peroxide and ascorbic acid through skin membranes can be monitored amperometrically. Skin membrane was fixed on the top of chemically modified electrodes and penetration of the appropriate compound was registered as electrode current. The methodology allows the study of penetration from solution as well as from pharmaceutical creams. From real-time measurements of electrode current, fluxes and diffusion coefficients of mentioned compounds in skin membranes have been estimated.
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| 20. |
- Gedeborg, Rolf, et al.
(författare)
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An Aggregated Comorbidity Measure Based on History of Filled Drug Prescriptions : Development and Evaluation in Two Separate Cohorts
- 2021
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Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 32:4, s. 607-615
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ability to account for comorbidity when estimating survival in a population diagnosed with cancer could be improved by using a drug comorbidity index based on filled drug prescriptions.Methods: We created a drug comorbidity index from age-stratified univariable associations between filled drug prescriptions and time to death in 326,450 control males randomly selected from the general population to men with prostate cancer. We also evaluated the index in 272,214 control females randomly selected from the general population to women with breast cancer.Results: The new drug comorbidity index predicted survival better than the Charlson Comorbidity Index (CCI) and a previously published prescription index during 11 years of follow-up. The concordance (C)-index for the new index was 0.73 in male and 0.76 in the female population, as compared with a C-index of 0.67 in men and 0.69 in women for the CCI. In men of age 75-84 years with CCI = 0, the median survival time was 7.1 years (95% confidence interval [CI] = 7.0, 7.3) in the highest index quartile. Comparing the highest to the lowest drug comorbidity index quartile resulted in a hazard ratio (HR) of 2.2 among men (95% CI = 2.1, 2.3) and 2.4 among women (95% CI = 2.3, 2.6).Conclusions: A new drug comorbidity index based on filled drug prescriptions improved prediction of survival beyond age and the CCI alone. The index will allow a more accurate baseline estimation of expected survival for comparing treatment outcomes and evaluating treatment guidelines in populations of people with cancer.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Holsti, Mari, 1963-, et al.
(författare)
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Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 56:1, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. Methods: This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta <= 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA >= 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Results: Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Conclusion: Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall.
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| 25. |
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| 26. |
- Jacobson, Sara, et al.
(författare)
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Hyperglycemia as a risk factor in pancreatic cancer : A nested case-control study using prediagnostic blood glucose levels
- 2021
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:6, s. 1112-1118
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples.METHODS: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test.RESULTS: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival.CONCLUSIONS: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.
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| 27. |
- Jansson, Malin, et al.
(författare)
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Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
- 2022
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is the most common cause of cancer death among women worldwide. Localized breast cancer can be cured by surgery and adjuvant therapy, but mortality remains high for tumors that metastasize early. Type IV collagen is a basement membrane protein, and breach of this extracellular matrix structure is the first step of cancer invasion. Type IV collagen is found in the stroma of many cancers, but its role in tumor biology is unclear. Here, expression of type IV collagen in the stroma of small breast cancers was analyzed, correlated to clinically used prognostic biomarkers and patient survival. The findings were further validated in an independent gene expression data cohort. Tissue samples from 1,379 women with in situ and small invasive breast cancers (<= 15 mm) diagnosed in 1986-2004 were included. Primary tumor tissue was collected into tissue microarrays. Type IV collagen expression in tissues was visualized using immunohistochemistry. Gene expression data was extracted from the Cancer Genome Atlas database. Out of 1,379 women, 856 had an invasive breast cancer and type IV collagen staining was available for 714 patients. In Kaplan-Meier analysis high type IV collagen expression was significantly associated (p = 0.026) with poorer breast cancer specific survival. There was no correlation of type IV collagen expression to clinically used prognostic biomarkers. High type IV collagen expression was clearly associated to distant metastasis (p = 0.002). In an external validation cohort (n = 1,104), high type IV collagen mRNA expression was significantly (p = 0.041) associated with poorer overall survival, with overexpression of type IV collagen mRNA in metastatic tissue. Stromal type IV collagen expression in the primary tumor correlates to poor breast cancer specific survival most likely due to a higher risk of developing distant metastasis. This ECM protein may function as biomarker to predict the risk of future metastatic disease in patients with breast cancers.
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| 28. |
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| 29. |
- Jansson, Malin, 1978-, et al.
(författare)
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Stromal type I collagen in breast cancer : correlation to prognostic biomarkers and prediction of chemotherapy response
- 2024
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Ingår i: Clinical Breast Cancer. - : Elsevier. - 1526-8209 .- 1938-0666.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fibrillar collagens accumulate in the breast cancer stroma and appear as poorly defined spiculated masses in mammography imaging. The prognostic value of tissue type I collagen remains elusive in treatment-naïve and chemotherapy-treated breast cancer patients. Here, type I collagen mRNA and protein expression were analysed in 2 large independent breast cancer cohorts. Levels were related to clinicopathological parameters, prognostic biomarkers, and outcome.Method: COL1A1 mRNA expression was analysed in 2509 patients with breast cancer obtained from the cBioPortal database. Type I collagen protein expression was studied by immunohistochemistry in 1395 women diagnosed with early invasive breast cancer.Results: Low COL1A1 mRNA and protein levels correlated with poor prognosis features, such as hormone receptor negativity, high histological grade, triple-negative subtype, node positivity, and tumour size. In unadjusted analysis, high stromal type I collagen protein expression was associated with improved overall survival (OS) (HR = 0.78, 95% CI = 0.61-0.99, p = .043) and trended towards improved breast cancer–specific survival (BCSS) (HR = 0.65, 95% CI = 0.42-1.01, P = 0.053), although these findings were lost after adjustment for other clinical variables. In unadjusted analysis, high expression of type I collagen was associated with better OS (HR = 0.70, 95% CI = 0.55-0.90, P = .006) and BCSS (HR = 0.55, 95% CI = 0.34-0.88, P = .014) among patients not receiving chemotherapy. Strikingly, the opposite was observed among patients receiving chemotherapy. There, high expression of type I collagen was instead associated with worse OS (HR = 1.83, 95% CI = 0.65-5.14, P = .25) and BCSS (HR = 1.72, 95% CI = 0.54-5.50, P = .357).Conclusion: Low stromal type I collagen mRNA and protein expression are associated with unfavourable tumour characteristics in breast cancer. Stromal type I collagen might predict chemotherapy response.
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| 30. |
- Lidström, Anna-Karin, et al.
(författare)
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Work at inpatient care units is associated with an increased risk of SARS-CoV-2 infection; a cross-sectional study of 8679 healthcare workers in Sweden.
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:4, s. 305-310
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: During the Covid-19 pandemic, the protection of healthcare workers has been in focus throughout the world, but the availability and quality of personal protective equipment has at times and in some settings been suboptimal.MATERIALS AND METHODS: A total of 8679 healthcare workers and healthcare support staff in the county of Uppsala, north of Stockholm, were included in this cross-sectional study. All subjects were analysed for IgG anti-SARS-CoV-2, and predictors for positive serostatus were analysed in a logistic regression model including demographic parameters and self-reported employment characteristics.RESULTS: Overall, 577 (6.6%) were classified as seropositive, with no statistically significant differences between healthcare workers and support staff. Among healthcare workers, age (OR 0.987 per year, 95% CI 0.980-0.995), time to sampling (OR 1.019 per day, 95% CI 1.004-1.035), and employment at an outpatient care unit (OR 0.620, 95% CI 0.487-0.788) were statistically significantly associated with risk of infection. Covid-19 specific units were not at particular risk, compared to other units with comparable characteristics and staff demography.CONCLUSION: Our findings indicate that SARS-CoV-2 transmission is related to inpatient healthcare work, and illustrate the need for a high standard of basic hygiene routines in all inpatient care settings.
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| 31. |
- Micke, Patrick, et al.
(författare)
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The prognostic impact of the tumour stroma fraction : A machine learning-based analysis in 16 human solid tumour types
- 2021
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns.Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR (95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59 (1.49-8.62)) associations of the tumour stroma fraction with survival.Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance.
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| 32. |
- Rask, Gunilla, et al.
(författare)
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Immune cell infiltrate in ductal carcinoma in situ and the risk of dying from breast cancer : case-control study
- 2024
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 111:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies identifying risk factors for death from breast cancer after ductal carcinoma in situ (DCIS) are rare. In this retrospective nested case-control study, clinicopathological factors in women treated for DCIS and who died from breast cancer were compared with those of patients with DCIS who were free from metastatic disease.Methods: The study included patients registered with DCIS without invasive carcinoma in Sweden between 1992 and 2012. This cohort was linked to the National Cause of Death Registry. Of 6964 women with DCIS, 96 were registered with breast cancer as cause of death (cases). For each case, up to four controls (318; women with DCIS, alive and without metastatic breast cancer at the time of death of the corresponding case) were selected randomly by incidence density sampling. Whole slides of tumour tissue were evaluated for DCIS grade, comedo necrosis, and intensity of periductal lymphocytic infiltrate. Composition of the immune cell infiltrate, expression of oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and proliferation marker Ki-67 were scored on tissue microarrays. Clinical information was obtained from medical records. Information on date, site, and histological characteristics of local and distant recurrences was obtained from medical records for both cases and controls.Results: Tumour tissue was analysed from 65 cases and 195 controls. Intense periductal lymphocytic infiltrate around DCIS was associated with an increased risk of later dying from breast cancer (OR 2.21. 95% c.i. 1.01 to 4.84). Tumours with more intense lymphocytic infiltrate had a lower T cell/B cell ratio. None of the other biomarkers correlated with increased risk of breast cancer death.Conclusion: The immune response to DCIS may influence the risk of dying from breast cancer.
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| 33. |
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| 34. |
- Sund, Johan, et al.
(författare)
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Continuous online fibre analysis enables improved pulp quality estimation and control
- 2022
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Ingår i: Proceedings of the International Mechanical Pulping Conference. ; , s. 99-106
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this work, high-rate fibre analysis has been used for direct feedback control of pulp quality by application of a new control strategy for a two-stage refining process in the Holmen Hallsta mill, Sweden. The application is based on control of pulp freeness, estimated from the continuous fibre analysis results from a BTG Single Point Morphology ana-lyzer. The goal was to create a robust and simple control strategy. The new strategy includes control of plate gap, con-sistency and the hydraulic force difference between the stages. Expressed as standard deviation, the freeness and av-erage fibre length variations were reduced by 50% and 25% respectively. The small size of the pulp chest in this process also benefits stronger feedback control. Long-term operation suggest that high-rate fibre analysis can be used to reduce faster quality variation.
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| 35. |
- Sund, Johan, et al.
(författare)
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The effect of process design on refiner pulp quality control performance
- 2021
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Ingår i: Nordic Pulp & Paper Research Journal. - : Walter de Gruyter GmbH. - 0283-2631 .- 2000-0669. ; 36:4, s. 594-607
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the effect of process- and online analyser configuration on pulp quality control is explored. The following parameters were included: analyser sampling interval, time delay, measurement error magnitude, and latency chest residence time. Using different values of parameters in a process model, a range of configurations were constructed. For each configuration, the achievable control performance was evaluated using an optimization approach. PI controller settings were chosen based on minimization of the integrated absolute error (IAE) in pulp quality after an input step disturbance. The results show that reducing the sampling interval improves performance also when the interval is smaller than the chest residence time or the analyser delay. Moreover, reducing the chest residence time can reduce the IAE by up to 40 %. However, reducing the residence time to lower than 1/3 of the sampling interval does not improve performance. Further improvement is possible if the analyser delay is reduced. The compromise between reducing the IAE and avoiding creating variation by acting on measurement error has a strong influence on the results. In conclusion, pulp quality control performance can be improved significantly by making changes to the studied configuration parameters.
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| 36. |
- Sund, Louise, 1970-, et al.
(författare)
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A transactional model of moral learning : How to challenge unsustainable denials
- 2023
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Ingår i: Environmental Education Research. - : Routledge. - 1350-4622 .- 1469-5871. ; 29:10, s. 1402-1416
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Tidskriftsartikel (refereegranskat)abstract
- This article draws on a philosophical critique of the problems of denial in the face of the climate crisis and the call for an education that deals with the root causes of social and environmental injustice in depth. To respond to this radical critique in concrete educational practice, there is a need for an understanding of moral learning that also considers the problems of denial and the role of the teacher in these learning processes. We therefore propose a transactional model grounded in Dewey’s pragmatic philosophy that explains how denial hinders the process of moral learning but also describes how teachers can offer moments of resistance that interrupt denial and challenges and transform moral habits. Finally, we discuss the implications of a transactional perspective and the need for making moral progress by reflectively revising our moral habits in the face of overlapping environmental and social injustice crises.
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| 37. |
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| 38. |
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| 39. |
- Sund, Louise, 1970-, et al.
(författare)
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Ethical reflections
- 2017
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Ingår i: Paper presented at the symposium: A Transactional Approach on ESD Research (Part 1)..
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Konferensbidrag (refereegranskat)abstract
- This contribution builds on an analytical approach using Dewey’s thoughts on morals and ethics to address how we acquire our morals, how we can reflect on moral situations, and how ethical reflections are visible in practice. In the study (Sund and Öhman, 2014) we investigate the variety of ethical reflections that emerge when a group of Swedish teachers participate in a study visit to Central America. Following Dewey, we investigated how a teacher, in interaction with others, finds a way to morally reason and co-ordinate with her or his surroundings. In this social co-construction things are literally made common—we socially construct the meaning of right and wrong and what works better in our lives, given the current problematic or situation.The study illustrates important possibilities for using Dewey’s perspective on morals and ethics in empirical studies. Firstly, ethical reflections are not hidden within humans’ minds but are available for empirical investigations of actions. Secondly, morality arises in relation to others and therefore needs to be investigated in relation to concrete and lived experiences. Thirdly, it demonstrates how ethical reflections can be investigated as processes of continuity and change. Lastly, the result underlines Dewey’s point that we need to move away from normative ethical theories and instead deepen the understanding of how humans try to co-ordinate their everyday actions with other people.
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| 40. |
- Sund, Louise, 1970-, et al.
(författare)
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Ethical Reflections on Intercultural interchanges
- 2016
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Ingår i: Paper presented at the symposium: A transactional perspective on meaning-making. Part 1. Ethical participation and ethical reflections..
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Konferensbidrag (refereegranskat)abstract
- The purpose of this symposium is to present a range of studies which use Dewey’s transactional perspective on meaning-making and practical epistemologies of education. In his influential work Democracy and Education (1916) John Dewey states that the basic role of education is to introduce the new generation to the knowledge and customs of previous members of a society. But a society consists of many practices and since different practices are based on different purposes, values and interests, the ideas that are held as true and good and the justified ways of making meaning differ between practices (Rorty 1991). To be a competent member of a society thus means being able to understand and make meanings in relation to a number of different practical epistemologies but also being capable of being critical of such epistemologies. The research group SMED (Studies of Meaning-making in Educational Discourses) has been engaged in the development of a methodology for analysing meaning-making processes where people are introduced to different practical epistemologies in educational settings. The methodology builds on John Dewey’s pragmatic philosophy and especially his concept of transaction (Dewey & Bentley 1949/1991). This perspective overcomes the methodological problems connected with the dualistic tendencies that trouble many other approaches to learning and classroom interactions. Within this approach meaning is not treated as something that exists within things themselves or in the minds of human beings, but is seen as the relations to the environment that is created in the processes of doing and undergoing the consequences of action. Such coordination is not restricted to knowledge but also involves ethical and aesthetical relations to the environment. Learning can thus be investigated in terms of actions, within a set of different practical epistemologies.
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| 41. |
- Sund, Louise, 1970-, et al.
(författare)
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Moral dilemmas in intercultural encounters – implications forESD
- 2012
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Konferensbidrag (refereegranskat)abstract
- Investing in cultural diversity and an intercultural dialogue is today regarded as one of the guiding principles within education for sustainable development (ESD) (Unesco 2009). A popular way of increasing intercultural understanding in order to deal with cultural diversity is by meeting – at eye-level – with people coming from other cultural backgrounds. We have studied teachers taking part in a Sida-funded in-service training programme called the Global Journey where the aim of the program is to foster intercultural dialogue and education in global issues for sustainable development in preschools, schools and adult education. Global Journeys provide opportunities for groups of Swedish teachers and educational professionals to spend an intense period of time in a developing country. The visits are part of a structured process of learning, planned a year in advance and evaluated four months after each journey.We believe that this aim to strengthen the linkage between culture and ESD can be seen as a turn to ethics in so far as it involves thinking about the ways in which we respond to otherness. Ethical issues arise in relation to others, between bodies – and there we also face our moral dilemmas. The aim of this paper is to study teachers’ moral meaning-making in a lived cultural encounter that involves moral and ethical judgements. We also would like to discuss the educational implications of cultural encounters such as Global Journeys and the educational value of traveling to meet the other.
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| 42. |
- Sund, Louise, 1970-
(författare)
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Om global etik i miljö- och hållbarhetsutbildningens policy och praktik
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis takes its point of departure in the change of emphasis in the field of environmental and sustainability education (ESE) towards the inclusion of social and human development issues. The theoretical frames of the thesis are poststructural and postcolonial theories, from which different writings, central concepts and approaches are drawn. The thesis also builds on a pragmatist and anti-essentialist approach which argues that we socially construct the meaning of right and wrong and what works better in our lives on the current problematic or situation. The results are presented in four studies and the thesis has three purposes. The first purpose is to describe and investigate theoretical perspectives that take a critical stand on and offer alternatives to universal and consensus-oriented approaches. This purpose is the central focus in the first and second studies. The first study examines the re-emergence of classical cosmopolitanism and contemporary views of the perspective with the intent of discussing its potential for the development of education for sustainable development (ESD). The second study aims to clarify the philosophical problem of addressing universally sustainable responsibilities and values in environmental and sustainability education. The second purpose is to investigate teachers’ ethical reflections in a first-hand intercultural experience. This purpose is dealt with in the third study, where seven Swedish upper secondary school teachers facing particular conflicts of interest and moral situations during a study visit to Central America are interviewed. The third purpose is to investigate how teachers deal with the complex issues of intragenerational equity or social justice in their teaching. This is dealt with in the fourth study, which explores how teachers integrate issues of social justice into their teaching of global sustainability. My hope is that this thesis will contribute to the discussion about how teachers can develop a conscious and critically informed approach to the teaching of environmental and sustainability issues and also contribute to theoretical and philosophical discussions about universalism, normativity and global ethics within environmental and sustainability education research.
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| 43. |
- Sund, Louise, 1970-, et al.
(författare)
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On the need to repoliticise environmental and sustainability education : rethinking the post-political consensus
- 2014
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Ingår i: Environmental Education Research. - : Routledge. - 1350-4622 .- 1469-5871. ; 20:5, s. 639-659
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Tidskriftsartikel (refereegranskat)abstract
- This article draws attention to the possibilities of the ongoing philosophical discussion about cosmopolitan universal values in relation to the normative challenges in environmental and sustainability education (ESE). The purpose of this paper is to clarify the philosophical problems of addressing universally sustainable responsibilities and values in ESE. Our arguments draw inspiration from the work of three poststructuralist scholars: we explore how Butler develops her claim that universal assertion requires a cultural translation, how Mouffe exposes the political in universal claim and how Todd argues that education needs to introduce students to a political language that enables them to critically reflect on their own and other groups’ values and actions. In the concluding part, we suggest the following guidelines for rethinking ESE: unmasking the political dimension, re-politicising education, seeing beyond the relativist and objectivist divide and using passion as a moving force.
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| 44. |
- Sund, Louise, 1970-, et al.
(författare)
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Poststructural criticism of cosmopolitanism : implications for education for sustainable development
- 2012
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Konferensbidrag (refereegranskat)abstract
- This paper draws attention to the possibilities of the qualified philosophical discussion about a cosmopolitan dilemma in the development of ESD. We argue that one challenge facing the development of ESD is the finding of balanced ways to deal with the normativity dilemma that take both the search for universal claims and particular contexts seriously.Taking the perspective of educational philosopher Sharon Todd, we explore how postmodernist thinking and a poststructural perspective balance between the cultivation of universal values and individuals’ autonomous thinking, and relate these approaches to ESD. Our claim is that ESD is in need of a critical discussion and exploration of ESD as a political project with dissonant voices that takes the particular human encounter into consideration.
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| 45. |
- Sund, Louise, 1970-, et al.
(författare)
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Swedish teachers’ ethical reflections on a study visit to Central America
- 2014
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Ingår i: Journal of Moral Education. - : Taylor & Francis Group. - 0305-7240 .- 1465-3877. ; 43:3, s. 316-331
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Tidskriftsartikel (refereegranskat)abstract
- In this article we argue that culturally variable values and morals have a key role in educational initiatives that address a global dimension. The article suggests that looking at values and morals in relation to a teaching practice is a way of adding knowledge to this field. Our study inquires into how an intercultural experience can evoke ethical reflections on environmental and sustainability issues. The article is based on a qualitative empirical study of teachers’ experiences of a teacher development programme, where we analyse the variety of ethical reflections that emerge during a study visit to a Central American country. We build on a pragmatic analytical approach that takes John Dewey’s ethical thoughts on moral situations as a point of departure and deals with teachers’ ethical reflections in a way that takes the contextual and situated nature of morals into account.
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| 46. |
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| 47. |
- Sund, Maria, 1983-, et al.
(författare)
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Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients : A population-based cohort study
- 2021
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Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 59, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors.METHODS: Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni- and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy.RESULTS: In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006-2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32-4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01-2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40-3.25 for arrhythmia; HR 2.03; 95% CI: 1.15-3.58 for ischemic heart disease).CONCLUSION: Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy.
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| 48. |
- Sund, Maria, 1983-, et al.
(författare)
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Estrogen therapy after breast cancer diagnosis and breast cancer mortality risk
- 2023
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 198:2, s. 361-368
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case-control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment.METHODS: In a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls.RESULTS: No statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use.CONCLUSIONS: The study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen.
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| 49. |
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| 50. |
- Tryggvason, Ásgeir, 1983-, et al.
(författare)
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Schooling and ESE : revisiting Stevenson’s gap from a pragmatist perspective
- 2022
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Ingår i: Environmental Education Research. - : Routledge. - 1350-4622 .- 1469-5871. ; 28:8, s. 1237-1250
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Tidskriftsartikel (refereegranskat)abstract
- Environmental and sustainability education (ESE) consists of topical existentialand ethical issues. At the same time, these issues are taught ina school setting that is shaped by assignments, grades, and school tasks.The relationships between structures of formal education in a schoolenvironment and the characteristics of ESE has been described in dichotomousterms as a contradiction, known in the ESE research field as“Stevenson’s gap”, after Robert B. Stevenson. The aim of this article is toovercome this dichotomous understanding of the relation betweenschooling and ESE by providing a pragmatist perspective. Drawing onJohn Dewey’s notion of habit, two learning habits are outlined by whichstudents encounter environmental and sustainability issues in the classroom:the habit of schooling and the habit of inquiry. Empirical data fromSwedish upper secondary schools is used to illustrate their meaning inclassroom practice. Our pragmatist conceptualisation highlights howthese habits are simultaneously present in the same classroom. A conclusionis that teaching and learning in ESE should not be reduced toeither habit but that both can be valuable for a robust and vital ESE.
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