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| 4. |
- Sten, S., et al.
(författare)
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Erik den heliges skelett
- 2016
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Ingår i: Fornvännen. - 0015-7813. ; 111:1, s. 27-40
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Tidskriftsartikel (refereegranskat)abstract
- No contemporary sources mention Erik Jedvardsson, Sweden's king saint. The only account of his life is the saint's legend, in its preserved form written in the late 13th century, and legends are notoriously untrustworthy. It says that in 1160, in the tenth year of Erik's reign, he was killed by a throne claimant. His remains have rested in a reliquary in Uppsala Cathedral since 1257 at the latest and survived the Reformation. A thorough investigation was made in 1946, and the development of new methods motivated a new investigation in 2014. 23 bones remain that apparently belong to the same individual. (They are accompanied in the reliquary by an unrelated shinbone.) Radiocarbon values are consistent with a death in 1160. The bones belong to a man, 35-40 years old, about 171 cm tall, without any discernible medical conditions. Bone density indicates a life of good nourishment and abundant exercise. The skull has one or two healed wounds that may have been due to weapons. Isotope analysis points to a diet rich in freshwater fish. Stable isotopes also imply that he did not spend his last decade in the expected Uppsala area but rather in Västergötland further south. Insufficient reference materials however make this a very preliminary conclusion. Samples for DNA analysis were collected, but the results are not expected for another year. The saint's legend says that in the king's final battle, the enemy swarmed him, and when he fell to the ground they gave him wound after wound until he lay half dead. They then taunted him and finally cut off his head. The remaining bones have at least nine cuts inflicted in connection with death, seven of them on the legs. No wounds have been found on the ribs or the remaining arm bone, which probably means that the king wore a hauberk but had less protected legs. Both shin bones have cuts inflicted from the direction of the feet, indicating that the victim lay on his front. A neck vertebra has been cut through, which could not have been done without removing the hau berk, i.e. not during battle. This confirms that there was an interlude, as described by the taunting in the legend, between battle and decapitation. At no point do the documented wounds gainsay the account of the fight given by the much later legend.
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| 5. |
- Van Den Berg, F. D., et al.
(författare)
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Product uniformity control - A research collaboration of european steel industries to non-destructive evaluation of microstructure and mechanical properties
- 2018
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Ingår i: Stud. Appl. Electromagn. Mech.. - : IOS Press. - 9781614998358 ; 43, s. 120-129
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Konferensbidrag (refereegranskat)abstract
- In steel manufacturing, the conventional method to determine the mechanical properties and microstructure is by offline, destructive (lab-)characterisation of sample material that is typically taken from the head or the tail of the coil. Since coils can be up to 7 km long, the samples are not always representative for the main coil body. Also, the time delay (typically a few days) between the actual production and the availability of the characterisation results implies that these results cannot be exploited for real-time adaptation of the process settings. Information about the microstructure and material properties can also be obtained from electromagnetic (EM) and ultrasonic (US) parameters, which can be measured in real-time, non-destructively, and over the full length of the steel strip product. With the aim to improve the consistency in product quality by use of inline EM and US measurements, a European project called "Product Uniformity Control" (PUC) has been set up as a broad collaboration between 4 major European Steel Manufacturers and 10 Universities / Research institutes. Using both numerical simulations and experimental characterisations, we study the inline measured EM and US parameters in regard of the microstructural and mechanical properties. In this way, we aim to establish an improved understanding of their mutual relationships, and to apply this knowledge in existing and new nondestructive evaluation techniques. In this paper, the concerted approach of modelling and experimental validation will be addressed, and results of this work will be shown in combination with inline measured data.
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| 6. |
- Wulaningsih, W., et al.
(författare)
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A competing risks analysis of the association between prediagnostic serum glucose and lipids and breast cancer survival
- 2016
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Ingår i: Cancer Research. - Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London WC2R 2LS, England. Kings Coll London, Inst Math & Mol Biomed, London WC2R 2LS, England. Uppsala Univ, Uppsala, Sweden. Reg Canc Ctr, Uppsala, Sweden. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Karolinska Inst, S-10401 Stockholm, Sweden. AstraZeneca R&D, Mlndal, Switzerland. CALAB Res, Madrid, Spain.. - 0008-5472 .- 1538-7445. ; 76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Berg, Frenk van den, et al.
(författare)
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Results of the European collaborative project "Product Uniformity Control" to improve the inline sensing of mechanical properties and microstructure of automotive steels
- 2018
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Ingår i: e-Journal of Nondestructive Testing (eJNDT). - 1435-4934. ; 23:8
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Tidskriftsartikel (refereegranskat)abstract
- A European consortium consisting of four major steel manufacturers and ten academic technology institutes has conducted a research and development project, called “Product Uniformity Control“ (PUC) in the period 2013 to 2017. This project aimed to develop and improve non-destructive (inline) measurement techniques to characterise the (uniformity of the) microstructure of steel strip products. In this project, a multitude of strip steel samples from various stages of production have been collected from the four participating steel manufacturers. The samples have been characterised in various ways, namely on their (1) non-destructive measurement parameters using different techniques suited for inline evaluation, (2) fundamental ultrasonic and electromagnetic properties (wave speed, ultrasonic attenuation, magnetisation loops, coercive field), (3) tensile properties (stress-strain curves) and (4) microstructure (by optical micrographs and EBSD images). The correlations between these different characterisations will be addressed. Besides the experimental characterisation, a strong accent has been on modelling activities: during the project, fundamental models have been developed to describe, starting from 2D and 3D microstructures, the ultrasonic and magnetic properties, which are next used as input to sensor models that predict the output of the inline measurement systems. This contribution presents the recent results of experimental work, which underlines the importance of associated modelling studies for the interpretation of the measurement data for the benefit of inline characterisation of the mechanical properties complementary to traditional destructive tensile testing.
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| 8. |
- Dyrskjot, L., et al.
(författare)
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Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
- 2012
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 107:8, s. 1392-1398
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio = 7.4 (95% confidence interval: 3.4-15.9), P < 0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.
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| 11. |
- Malmström, Erik, et al.
(författare)
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Targeted mass spectrometry analysis of neutrophil-derived proteins released during sepsis progression.
- 2014
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 112:6, s. 1230-1243
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Tidskriftsartikel (refereegranskat)abstract
- Early diagnosis of severe infectious diseases is essential for timely implementation of lifesaving therapies. In a search for novel biomarkers in sepsis diagnosis we focused on polymorphonuclear neutrophils (PMNs). Notably, PMNs have their protein cargo readily stored in granules and following systemic stimulation an immediate increase of neutrophil-borne proteins can be observed into the circulation of sepsis patients. We applied a combination of mass spectrometry (MS) based approaches, LC-MS/MS and selected reaction monitoring (SRM), to characterise and quantify the neutrophil proteome in healthy or disease conditions. With this approach we identified a neutrophil-derived protein abundance pattern in blood plasma consisting of 20 proteins that can be used as a protein signature for severe infectious diseases. Our results also show that SRM is highly sensitive, specific, and reproducible and, thus, a promising technology to study a complex, dynamic and multifactorial disease such as sepsis.
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| 12. |
- Nadafi, Reza, et al.
(författare)
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Dendritic cell migration to skin-draining lymph nodes is controlled by dermatan sulfate and determines adaptive immunity magnitude
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:FEB
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Tidskriftsartikel (refereegranskat)abstract
- For full activation of naïve adaptive lymphocytes in skin-draining lymph nodes (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived dendritic cells (DCs) that encountered antigens (Ags) is an absolute prerequisite. To get to the nearest draining LN upon intradermal immunization, DCs need to migrate from the infection site to the afferent lymphatics, which can only be reached by traversing a collagen-dense network located in the dermis of the skin through the activity of proteolytic enzymes. Here, we show that mice with altered collagen fibrillogenesis resulting in thicker collagen fibers in the skin display a reduced DC migration to the draining LN upon immune challenge. Consequently, the initiation of the cellular and humoral immune response was diminished. Ag-specific CD8+ and CD4+ T cells as well as Ag-specific germinal center B cells and serum immunoglobulin levels were significantly decreased. Hence, we postulate that alterations to the production of extracellular matrix, as seen in various connective tissue disorders, may in the end affect the qualitative outcome of adaptive immunity.
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| 14. |
- van Thuijl, Hinke F., et al.
(författare)
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Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment
- 2015
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Ingår i: Acta Neuropathologica. - : Springer Verlag (Germany). - 0001-6322 .- 1432-0533. ; 129:4, s. 597-607
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Tidskriftsartikel (refereegranskat)abstract
- Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O (6) -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-na less than ve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.
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| 15. |
- Bonnefoi, H., et al.
(författare)
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Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 25:6, s. 1128-1136
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Tidskriftsartikel (refereegranskat)abstract
- Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis.
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| 16. |
- Darby, S, et al.
(författare)
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Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death : meta-analysis of individual patient data for 10,801 women in 17 randomised trials
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9804, s. 16-1707
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk.METHODS: We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease.FINDINGS: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7-17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6-6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2-17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8-5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (≥20%), intermediate (10-19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1-12·5), 1·1% (-2·0 to 4·2), and 0·1% (-7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5-27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8-15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease.INTERPRETATION: After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made.FUNDING: Cancer Research UK, British Heart Foundation, and UK Medical Research Council.
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| 17. |
- Davies, C, et al.
(författare)
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Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen : patient-level meta-analysis of randomised trials
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9793, s. 771-784
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen. METHODS: We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21,457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment. FINDINGS: In oestrogen receptor (ER)-positive disease (n=10,645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0-4 and RR 0·68 [0·06] during years 5-9 [both 2p<0·00001]; but RR 0·97 [0·10] during years 10-14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10-19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0·71 [0·05] during years 0-4, 0·66 [0·05] during years 5-9, and 0·68 [0·08] during years 10-14; p<0·0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality. INTERPRETATION: 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the only recorded factor importantly predictive of the proportional reductions. Hence, the absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamoxifen. FUNDING: Cancer Research UK, British Heart Foundation, and Medical Research Council.
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| 20. |
- Green, Henrik, et al.
(författare)
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Pegylated liposomal doxorubicin as first-line monotherapy in elderly women with locally advanced or metastatic breast cancer : Novel treatment predictive factors identified
- 2011
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 313:2, s. 145-153
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the efficacy and safety of single-agent pegylated liposomal doxorubicin (PLD) as first-line treatment for elderly women with advanced breast cancer and evaluated predictive markers for response and toxicity. Twenty-five women >= 65 years received 40 mg/m(2) PLD every 28 days. Time to treatment failure (TTF), response rate, time to progression (TTP) and overall survival (OS) was calculated. The ABCB1 single nucleotide polymorphisms (SNP), tumor MRN complex, and TOPOII alpha were analyzed. A mean of 7.4 cycles PLD were administered and TIT was 5.5 months and OS 20.6 months. ABCB1 SNPs were found to correlate to both efficacy and toxicity, while tumor expression of the MRN complex and TOPOII alpha correlated to TTP. PLD is a safe and effective treatment for elderly breast cancer patients. Also potential predictive markers were identified.
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| 21. |
- Hatton, Fiona L., et al.
(författare)
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Xyloglucan-Functional Latex Particles via RAFT-Mediated Emulsion Polymerization for the Biomimetic Modification of Cellulose
- 2016
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 17:4, s. 1414-1424
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we report a novel class of latex particles composed of a hemicellulose, xyloglucan (XG), and poly(methyl methacrylate) (PMMA), specially designed to enable a biomimetic modification of cellulose. The formation of the latex particles was achieved utilizing reversible addition-fragmentation chain transfer (RAFT) mediated surfactant-free emulsion polymerization employing XG as a hydrophilic macromolecular RAFT agent (macroRAFT). In an initial step, XG was functionalized at the reducing chain end to bear a dithioester. This XG macroRAFT was subsequently utilized in water and chain extended with methyl methacrylate (MMA) as hydrophobic monomer, inspired by a polymerization-induced self-assembly (PISA) process. This yielded latex nanoparticles with a hydrophobic PMMA core stabilized by the hydrophilic XG chains at the corona. The molar mass of PMMA targeted was varied, resulting in a series of stable latex particles with hydrophobic PMMA content between 22 and 68 wt % of the total solids content (5-10%). The XG-PMMA nanoparticles were subsequently adsorbed to a neutral cellulose substrate (filter paper), and the modified surfaces were analyzed by FT-IR and SEM analyses. The adsorption of the latex particles was also investigated by quartz crystal microbalance with dissipation monitoring (QCM-D), where the nanoparticles were adsorbed to negatively charged model cellulose surfaces. The surfaces were analyzed by atomic force microscopy (AFM) and contact angle (CA) measurements. QCM-D experiments showed that more mass was adsorbed to the surfaces with increasing molar mass of the PMMA present. AFM of the surfaces after adsorption showed discrete particles, which were no longer present after annealing (160 °C, 1 h) and the roughness (Rq) of the surfaces had also decreased by at least half. Interestingly, after annealing, the surfaces did not all become more hydrophobic, as monitored by CA measurements, indicating that the surface roughness was an important factor to consider when evaluating the surface properties following particle adsorption. This novel class of latex nanoparticles provides an excellent platform for cellulose modification via physical adsorption. The utilization of XG as the anchoring molecule to cellulose provides a versatile methodology, as it does not rely on electrostatic interactions for the physical adsorption, enabling a wide range of cellulose substrates to be modified, including neutral sources such as cotton and bacterial nanocellulose, leading to new and advanced materials.
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| 22. |
- Hedegaard, Jakob, et al.
(författare)
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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
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Tidskriftsartikel (refereegranskat)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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| 23. |
- Kamat, Ashish M, et al.
(författare)
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Bladder cancer
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10061, s. 2796-2810
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Forskningsöversikt (refereegranskat)abstract
- Bladder cancer is a complex disease associated with high morbidity and mortality rates if not treated optimally. Awareness of haematuria as the major presenting symptom is paramount, and early diagnosis with individualised treatment and follow-up is the key to a successful outcome. For non-muscle-invasive bladder cancer, the mainstay of treatment is complete resection of the tumour followed by induction and maintenance immunotherapy with intravesical BCG vaccine or intravesical chemotherapy. For muscle-invasive bladder cancer, multimodal treatment involving radical cystectomy with neoadjuvant chemotherapy offers the best chance for cure. Selected patients with muscle-invasive tumours can be offered bladder-sparing trimodality treatment consisting of transurethral resection with chemoradiation. Advanced disease is best treated with systemic cisplatin-based chemotherapy; immunotherapy is emerging as a viable salvage treatment for patients in whom first-line chemotherapy cannot control the disease. Developments in the past 2 years have shed light on genetic subtypes of bladder cancer that might differ from one another in response to various treatments.
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| 25. |
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| 26. |
- Lund, M, et al.
(författare)
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Nitric oxide and endothelin-1 release after one-lung ventilation during thoracoabdominal esophagectomy.
- 2013
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Ingår i: Diseases of the esophagus. - : Oxford University Press (OUP). - 1120-8694. ; 26:8, s. 853-858
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Tidskriftsartikel (refereegranskat)abstract
- One-lung ventilation (OLV) is applied during esophagectomy to improve exposure during the thoracic part of the operation. Collapse of lung tissue, shunting of pulmonary blood flow, and changes in alveolar oxygenation during and after OLV may possibly induce an ischemia-reperfusion response in the lung, which may affect the pulmonary endothelium. Such a reaction might thereby contribute to the frequently occurring respiratory complications among these patients. In this small trial, 30 patients were randomized to either OLV (n= 16) or two-lung ventilation (TLV, n= 14) during esophagectomy. Central venous and arterial plasma samples were taken before and after OLV/TLV for analysis of nitrite and a metabolite of nitric oxide (NO), and also during the 1st, 2nd, 3rd, and 10th postoperative day for analysis of endothelin, another endothelium-derived vasoactive mediator. Lung biopsies were taken before and after OLV or TLV, and analyzed regarding immunofluorescence for isoform of NO synthase, a protein upregulated during inflammatory response and also vascular congestion. No changes in lung isoform of NO synthase immunofluorescence or vascular congestion were registered after neither OLV nor TLV. Plasma nitrite and endothelin levels were similar in the two study groups. We conclude that OLV does not seem to have any influence on key regulators of pulmonary vascular tone and inflammation, i.e. NO and endothelin. From this perspective, OLV seems to be a safe method, which defends its clinical position to facilitate surgical exposure during thoracoabdominal esophagectomy.
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| 27. |
- Lødrup Carlsen, K C, et al.
(författare)
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Assessment of problematic severe asthma in children.
- 2011
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 37:2, s. 432-40
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of problematic severe asthma in children should be performed in a step-wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients.
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| 31. |
- Raghavan, Maanasa, et al.
(författare)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
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Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 34. |
- Valdiosera, Cristina, et al.
(författare)
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Four millennia of Iberian biomolecular prehistory illustrate the impact of prehistoric migrations at the far end of Eurasia
- 2018
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:13, s. 3428-3433
-
Tidskriftsartikel (refereegranskat)abstract
- Population genomic studies of ancient human remains have shown how modern-day European population structure has been shaped by a number of prehistoric migrations. The Neolithization of Europe has been associated with large-scale migrations from Anatolia, which was followed by migrations of herders from the Pontic steppe at the onset of the Bronze Age. Southwestern Europe was one of the last parts of the continent reached by these migrations, and modern-day populations from this region show intriguing similarities to the initial Neolithic migrants. Partly due to climatic conditions that are unfavorable for DNA preservation, regional studies on the Mediterranean remain challenging. Here, we present genome-wide sequence data from 13 individuals combined with stable isotope analysis from the north and south of Iberia covering a four-millennial temporal transect (7,500-3,500 BP). Early Iberian farmers and Early Central European farmers exhibit significant genetic differences, suggesting two independent fronts of the Neolithic expansion. The first Neolithic migrants that arrived in Iberia had low levels of genetic diversity, potentially reflecting a small number of individuals; this diversity gradually increased over time from mixing with local hunter-gatherers and potential population expansion. The impact of post-Neolithic migrations on Iberia was much smaller than for the rest of the continent, showing little external influence from the Neolithic to the Bronze Age. Paleodietary reconstruction shows that these populations have a remarkable degree of dietary homogeneity across space and time, suggesting a strong reliance on terrestrial food resources despite changing culture and genetic make-up.
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| 35. |
- Allemani, Claudia, et al.
(författare)
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Breast cancer survival in the US and Europe: a CONCORD high-resolution study
- 2013
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 132:5, s. 1170-1181
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardized survival. The aim of this study is to explain these survival differences. Population-based data on stage at diagnosis, diagnostic procedures, treatment and follow-up were collected for about 20,000 women diagnosed with breast cancer aged 15-99 years during 1996-98 in 7 US states and 12 European countries. Age-standardized net survival and the excess hazard of death up to 5 years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node-negative tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5-6%). Net survival in Northern, Western and Southern Europe (81-84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70-99 years, and mainly confined to women with locally advanced or metastatic tumors. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment.
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| 36. |
- Bartolini, Barbara, et al.
(författare)
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Iduronic Acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
-
Tidskriftsartikel (refereegranskat)abstract
- Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK) and phospho-FAK (pFAK) was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis.
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| 37. |
- Bergenudd, Helena, 1978-
(författare)
-
Understanding the mechanisms behind atom transfer radical polymerization : exploring the limit of control
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atom transfer radical polymerization (ATRP) is one of the most commonly employed techniques for controlled radical polymerization. ATRP has great potential for the development of new materials due to the ability to control molecular weight and polymer architecture. To fully utilize the potential of ATRP as polymerization technique, the mechanism and the dynamics of the ATRP equilibrium must be well understood. In this thesis, various aspects of the ATRP process are explored through both laboratory experiments and computer modeling. Solvent effects, the limit of control and the use of iron as the mediator have been investigated. It was shown for copper mediated ATRP that the redox properties of the mediator and the polymerization properties were significantly affected by the solvent. As expected, the apparent rate constant (kpapp) increased with increasing activity of the mediator, but an upper limit was reached, where after kpapp was practically independent of the mediator potential. The degree of control deteriorated as the limit was approached. In the simulations, which were based on the thermodynamic properties of the ATRP equilibrium, the same trend of increasing kpapp with increasing mediator activity was seen and a maximum was also reached. The simulation results could be used to describe the limit of control. The maximum equilibrium constant for controlled ATRP was correlated to the propagation rate constant, which enables the design of controlled ATRP systems. Using iron compounds instead of copper compounds as mediators in ATRP is attractive from environmental aspects. Two systems with iron were investigated. Firstly, iron/EDTA was investigated as mediator as its redox properties are within a suitable range for controlled ATRP. The polymerization of styrene was heterogeneous, where the rate limiting step is the adsorption of the dormant species to the mediator surface. The polymerizations were not controlled and it is possible that they had some cationic character. In the second iron system, the intention was to investigate how different ligands affect the properties of an ATRP system with iron. Due to competitive coordination of the solvent, DMF, the redox and polymerization properties were not significantly affected by the ligands. The differences between normal and reverse ATRP of MMA, such as the degree of control, were the result of different FeIII speciation in the two systems.
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| 38. |
- Blomkvist, Marita, 1959, et al.
(författare)
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Accounting knowledge in innovative firms – direct contacts with external auditors for strategic actions.
- 2016
-
Ingår i: International Journal of Managerial and Financial Accounting. - 1753-6715 .- 1753-6723. ; 8:3/4, s. 209-229
-
Tidskriftsartikel (refereegranskat)abstract
- Managers' use of auditors in decision processes is well known in the accounting literature, but little is known about owner-managers in innovative firms and their acquisition of accounting knowledge through direct contacts with external auditors. We conducted a multiple embedded study of exploratory character based on 21 interviews with owner-managers and external auditors connected to six innovative firms. We show that owner-managers in innovative firms apply informal management control in early phases of the innovation process and thus also rely heavily on external auditors for such purposes. However, management's acquisition of accounting knowledge may contribute over time to the development of a more formalised control system as their competence increases. This study suggests that a competence-based view may be useful for understanding the role of accounting and external auditors in innovative firms' management control systems. Managers' use of auditors in decision processes is well known in the accounting literature, but little is known about owner-managers in innovative firms and their acquisition of accounting knowledge through direct contacts with external auditors. We conducted a multiple embedded study of exploratory character based on 21 interviews with owner-managers and external auditors connected to six innovative firms. We show that owner-managers in innovative firms apply informal management control in early phases of the innovation process and thus also rely heavily on external auditors for such purposes. However, management's acquisition of accounting knowledge may contribute over time to the development of a more formalised control system as their competence increases. This study suggests that a competence-based view may be useful for understanding the role of accounting and external auditors in innovative firms' management control systems. Managers' use of auditors in decision processes is well known in the accounting literature, but little is known about owner-managers in innovative firms and their acquisition of accounting knowledge through direct contacts with external auditors. We conducted a multiple embedded study of exploratory character based on 21 interviews with owner-managers and external auditors connected to six innovative firms. We show that owner-managers in innovative firms apply informal management control in early phases of the innovation process and thus also rely heavily on external auditors for such purposes. However, management's acquisition of accounting knowledge may contribute over time to the development of a more formalised control system as their competence increases. This study suggests that a competence-based view may be useful for understanding the role of accounting and external auditors in innovative firms' management control systems.
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| 39. |
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| 40. |
- Carlsson, Linn, et al.
(författare)
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Modification of cellulose model surfaces by cationic polymer latexes prepared by RAFT-mediated surfactant-free emulsion polymerization
- 2014
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Ingår i: Polymer Chemistry. - : Royal Society of Chemistry. - 1759-9954 .- 1759-9962. ; 5:20, s. 6076-6086
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the successful surface modification of a model cellulose substrate by the preparation and subsequent physical adsorption of cationic polymer latexes. The first part of the work introduces novel charged polymer nanoparticles constituted of amphiphilic block copolymers based on cationic poly(N,N-dimethylaminoethyl methacrylate-co-methacrylic acid) (P(DMAEMA-co-MAA)) as the hydrophilic segment, and poly(methyl methacrylate) (PMMA) as the hydrophobic segment. First, RAFT polymerization of N,N-dimethylaminoethyl methacrylate (DMAEMA) in water was performed at pH 7, below its pKa. The simultaneous hydrolysis of DMAEMA led to the formation of a statistical copolymer incorporating mainly protonated DMAEMA units and some deprotonated methacrylic acid units at pH 7. The following step was the RAFT-mediated surfactant-free emulsion polymerization of methyl methacrylate (MMA) using P(DMAEMA-co-MAA) as a hydrophilic macromolecular RAFT agent. During the synthesis, the formed amphiphilic block copolymers self-assembled into cationic latex nanoparticles by polymerization-induced self-assembly (PISA). The nanoparticles were found to increase in size with increasing molar mass of the hydrophobic block. The cationic latexes were subsequently adsorbed to cellulose model surfaces in a quartz crystal microbalance equipment with dissipation (QCM-D). The adsorbed amount, in mg m-2, increased with increasing size of the nanoparticles. This approach allows for physical surface modification of cellulose, utilizing a water suspension of particles for which both the surface chemistry and the surface structure can be altered in a well-defined way.
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| 41. |
- Carlsson, Linn, 1985-
(författare)
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Surface Modification of Cellulose by Covalent Grafting and Physical Adsorption
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interest in new environmentally friendly cellulose‐based productshas increased tremendously over the last years. At the same time theSwedish forest industry faces new challenges in its strive to increase the utilization of cellulose fibers in high‐value end‐products. The aim of this study was to expand the toolbox for surface modification of cellulose byemploying covalent surface‐initiated (SI) polymerizations or by physicaladsorption of polymers. SI‐ring‐opening polymerization (ROP) of ε‐caprolactone (ε‐CL) was performed from filter paper (FP) and high surface area nanopaper (NP).Larger amounts of polycaprolactone (PCL) were grafted from NP, compared to FP, owing to the higher amount of available initiating hydroxyl groups. Furthermore, the mechanical properties of PCL were improved by the grafting of FP and NP, as compared to pure PCL.It is challenging to characterize a polymer grafted from a surface. Hence, quartz crystal microbalance with dissipation (QCM‐D) was employed to investigate SI‐ROP in real time from a cellulose model surface. Furthermore, it was shown by colloidal probe AFM that increased lengthof grafted PCL, from cellulose microspheres, improved the interfacialadhesion to a pure PCL surface, suggesting that chain entanglements havea significant impact on the interfacial properties. Increased temperatureand time in contact also improved the adhesion.In order to investigate the degree of substitution (DS) and the degree of polymerization (DP), PCL‐grafted hydrolyzed cellulose cotton linters (HCCL) were studied by solid state NMR. It was found that despite a DS of only a few percent, the surface character changed considerably; furthermore, the DS was virtually independent of the DP. To increase theamount of grafted polymer, ring‐opening metathesis polymerization (ROMP) of norbornene was performed from FP. Short polymerizationtimes and low temperatures resulted in highly grafted surfaces. Alternatively, physical adsorption by electrostatic interactions was employed to modify a cellulose model surface in the QCM‐D. Cationic latex nanoparticles of poly(dimetylaminoethyl methacrylate‐co‐methacrylicacid)‐block‐poly(methyl methacrylate) were produced by reversible addition‐fragmentation chain‐transfer (RAFT)‐mediated surfactant‐freeemulsion polymerization by polymerization‐induced self‐assembly (PISA).This strategy does not require any organic solvents and could potentiallybe introduced in industrial processes.
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| 42. |
- Cars, Thomas, et al.
(författare)
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Effectiveness of Drugs in Routine Care : A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example
- 2018
-
Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 103:3, s. 493-501
-
Tidskriftsartikel (refereegranskat)abstract
- Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different fromthose treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases froma well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.
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| 43. |
- Chan, Owen T. M., et al.
(författare)
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Association of MMP-2, RB and PAI-1 with decreased recurrence-free survival and overall survival in bladder cancer patients
- 2017
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:59, s. 99707-99721
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We previously reported an accurate urine-based bladder cancer (BCa)-associated diagnostic signature that can be used to non-invasively detect BCa. In this study, we investigated whether a component of this signature could risk stratify patients with BCa. Methods: Utilizing immunohistochemistry, we investigated angiogenin, MMP-2, p53, RB and PAI-1 expression from 939 patients with BCa. The expression levels were scored by assigning a proportion score and an intensity score to yield a total staining score for each protein. The expressions of each protein individually and as an aggregate were then correlated with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Results: Differential expressions of these markers were noted in BCa. With multivariate analysis in non-muscle invasive bladder cancer (NMIBC) age, tumor grade portended a worse PFS, while age, tumor grade, nodal status, MMP2, RB and PAI-1 expression portended a worse OS. As for multivariate analysis in muscle invasive bladder cancer (MIBC), age MMP-2 and RB were associated with a worse PFS, while age, nodal status, MMP-2, RB and PAI-1 were associated with a worse OS. Using Kaplan-Meier survival analysis, we noted a significant reduction in OS as more of the five biomarkers were expressed in a tumor. Thus, overall, high expressions of MMP-2, RB and/or PAI-1 in bladder tumors were markers of poor prognosis. Conclusion: Individually, MMP-2, RB and PAI-1, as well as in aggregate correlated with poor survival in patients with BCa. Thus, patients whose bladder tumors express these biomarkers may benefit from early radical treatment and/or neoadjuvant or adjuvant therapies.
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| 44. |
- Chen, Kenneth, et al.
(författare)
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Recommendations for Core Outcome Domain Set for Whiplash Associated Disorders (CATWAD)
- 2019
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Ingår i: Clinical Journal of Pain. - : Lippincott Williams & Wilkins. - 0749-8047 .- 1536-5409. ; 35:9, s. 727-736
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Inconsistent reporting of outcomes in clinical trials of treatments for Whiplash Associated Disorders (WAD) hinders effective data pooling and conclusions that can be drawn about the effectiveness of tested treatments. The aim of this study was to provide recommendations for core outcome domains that should be included in clinical trials of WAD. Methods: A three-step process was used. 1) A list of potential core outcome domains were identified from the published literature; 2) Researchers, health care providers, patients and insurance personnel participated and rated the importance of each domain via a three round Delphi survey. A priori criteria for consensus were established; 3) Experts comprising researchers, health care providers and a consumer representative participated in a multidisciplinary consensus meeting that made final decisions on the recommended core outcome domains. Results: The literature search identified 63 potential core domains. 223 participants were invited to partake in the Delphi surveys with 41.7% completing Round 1, 45.3% Round 2 and 51.4% Round 3. Eleven core domains met the criteria for inclusion across the entire sample. After the expert consensus meeting, six core domains were recommended: Physical Functioning, Perceived Recovery, Work and Social Functioning, Psychological Functioning, Quality of Life and Pain. Discussion: A 3-step process was used to recommend core outcome domains for clinical trials in WAD. Six core domains were recommended: Physical Functioning, Perceived Recovery, Work and Social Functioning, Psychological Functioning, Quality of Life and Pain. The next step is to determine the outcome measurement instruments for each of these domains.
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| 45. |
- Chen, Yen Hsi, et al.
(författare)
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The GAGOme : a cell-based library of displayed glycosaminoglycans
- 2018
-
Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 15:11, s. 881-888
-
Tidskriftsartikel (refereegranskat)abstract
- Glycosaminoglycans (GAGs) are essential polysaccharides in normal physiology and disease. However, understanding of the contribution of specific GAG structures to specific biological functions is limited, largely because of the great structural heterogeneity among GAGs themselves, as well as technical limitations in the structural characterization and chemical synthesis of GAGs. Here we describe a cell-based method to produce and display distinct GAGs with a broad repertoire of modifications, a library we refer to as the GAGOme. By using precise gene editing, we engineered a large panel of Chinese hamster ovary cells with knockout or knock-in of the genes encoding most of the enzymes involved in GAG biosynthesis, to generate a library of isogenic cell lines that differentially display distinct GAG features. We show that this library can be used for cell-based binding assays, recombinant expression of proteoglycans with distinct GAG structures, and production of distinct GAG chains on metabolic primers that may be used for the assembly of GAG glycan microarrays.
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| 46. |
- Dahlrot, R. H., et al.
(författare)
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Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis
- 2018
-
Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 44:2, s. 172-184
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Tidskriftsartikel (refereegranskat)abstract
- Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status.Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population‐based Region of Southern Denmark (RSD)‐cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM‐patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules.Results: When divided at the median, patients with low expression of MGMT protein (AF‐low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS‐cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF‐low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF‐low had the best outcome; median OS 23.1 and 20.0 months, respectively.Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour‐specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.
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| 47. |
- Engström, Joakim, et al.
(författare)
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Soft and rigid core latex nanoparticles prepared by RAFT-mediated surfactant-free emulsion polymerization for cellulose modification-a comparative study
- 2017
-
Ingår i: Polymer Chemistry. - : Royal Society of Chemistry. - 1759-9954 .- 1759-9962. ; 8:6, s. 1061-1073
-
Tidskriftsartikel (refereegranskat)abstract
- Latex nanoparticles comprising cationically charged coronas and hydrophobic cores with different glass transition temperatures (Tg) have been prepared by surfactant-free, RAFT-mediated emulsion polymerization, where the particles form through a polymerization-induced self-assembly (PISA) type mechanism. Poly(2-dimethylaminoethyl methacrylate-co-methacrylic acid) (P(DMAEMA-co-MAA)) was utilized as a hydrophilic macroRAFT agent for the polymerization of methyl methacrylate (MMA) or n-butyl methacrylate (nBMA), respectively, resulting in two different latexes, with either a core of high (PMMA) or low (PnBMA) Tg polymer. By varying the molar mass of the hydrophobic block, latexes of different sizes were obtained (DHca. 40-120 nm). The adsorption of the latexes to cellulose model surfaces and cellulose nanofibrils (CNF) was studied using quartz crystal microbalance with dissipation monitoring (QCM-D). The surfaces with adsorbed PnBMA latexes yielded hydrophobic surfaces both before and after annealing, whereas surfaces with adsorbed PMMA latex became hydrophobic only after annealing, clearly showing the influence of the Tg of the core. The latexes were also used to modify macroscopic cellulose in the form of filter papers. Similar to the CNF surfaces, no annealing was required to achieve hydrophobic surfaces with PnBMA latexes. Finally, nanocomposites of CNF and the polymer nanoparticles were prepared through a one-pot mixing procedure. It was found that the largest synthesized PMMA latex (120 nm) facilitated a more strainable CNF network at 50% relative humidity, with a nearly 200% increase in strain at break compared to the neat CNF reference film as well as to the composite films with PnBMA latexes or to the smaller sized PMMA latexes. This difference was attributed to the spherical shape and rigidity of the large PMMA latex nanoparticles during composite formation. This highly interesting result should indeed be considered in the future design of novel biocomposites.
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| 48. |
- Eriksson, Magnus G., et al.
(författare)
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One-pot enzymatic polycondensation to telechelic methacrylate-functional oligoesters used for film formation
- 2011
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Ingår i: POLYM CHEM. - Cambridge : ROYAL SOC CHEMISTRY. - 1759-9954 .- 1759-9962. ; 2:3, s. 714-719
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Tidskriftsartikel (refereegranskat)abstract
- Based on largely renewable monomers, an enzymatic one-pot polycondensation route towards functional oligomers with targeted molecular weights and end-groups was developed. This one-pot synthesis was performed by combining Candida antarctica lipase B (CALB), 2-hydroxyethyl methacrylate (HEMA), ethylene glycol, and divinyl adipate under reduced pressure (72 mbar) at 60 degrees C. The polymerization went to completion (>95% conversion for all monomers) within 24 h and the fraction of methacrylate end-groups was >90%. Three targeted dimethacrylate functional oligomers with molecular weights of 920, 1700 and 2500 g mol(-1) (degrees of polymerization 4, 8, and 13 respectively) were synthesized. The oligomer products were characterized by NMR, MALDI-TOF MS and SEC. The dimethacrylate functional oligomers were further UV homopolymerized or combined with a tetrathiol crosslinker to demonstrate the potential to produce novel networks with tunable thermal properties dependent on chain length of the telechelic building blocks. This research is the first to demonstrate methacrylate functionalization and condensation polymerization in a one step process, which expands the growing toolbox for polymer/material chemists towards an increased throughput in available macromonomers used in material design.
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| 49. |
- Furst, Camilla Melin, et al.
(författare)
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Quantitative mass spectrometry to study inflammatory cartilage degradation and resulting interactions with the complement system
- 2016
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 197:8, s. 3415-3424
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Tidskriftsartikel (refereegranskat)abstract
- Joint diseases are often characterized by inflammatory processes that result in pathological changes in joint tissues, including cartilage degradation and release of components into the synovial fluid. The complement system plays a central role in promoting the inflammation. Because several cartilage proteins are known to interact with complement, causing either activation or inhibition of the system, we aimed to investigate these interactions comprehensively. Bovine cartilage explants were cultured with IL-1α to induce cartilage degradation, followed by incubation with human serum. Label-free selected reaction monitoring mass spectrometry was used to specifically quantify complement proteins interacting with the cartilage explant. In parallel, the time-dependent degradation of cartilage was detected using mass spectrometry analysis (liquid chromatography-tandem mass spectrometry). Complement proteins resulting from activation of the classical, alternative, and terminal pathways were detected on IL-1α-stimulated cartilage at time points when clear alterations in extracellular matrix composition had occurred. Increased levels of the complement activation product C4d, as detected by ELISA in serum after incubation with IL-1α-stimulated cartilage, confirmed the selected reaction monitoring results indicating complement activation. Further, typical activated (cleaved) C3 fragments were detected by Western blotting in extracts of IL-1α-stimulated cartilage. No complement activation was triggered by cartilage cultured in the absence of IL-1α. Components released from IL-1α-stimulated cartilage during culture had an inhibitory effect on complement activation. These were released after a longer incubation period with IL-1α and may represent a feedback reaction to cartilage-triggered complement activation observed after a shorter incubation period.
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| 50. |
- Günther, Torsten, et al.
(författare)
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Ancient genomes link early farmers from Atapuerca in Spain to modern-day Basques
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:38, s. 11917-11922
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Tidskriftsartikel (refereegranskat)abstract
- The consequences of the Neolithic transition in Europe-one of the most important cultural changes in human prehistory-is a subject of great interest. However, its effect on prehistoric and modern-day people in Iberia, the westernmost frontier of the European continent, remains unresolved. We present, to our knowledge, the first genome-wide sequence data from eight human remains, dated to between 5,500 and 3,500 years before present, excavated in the El Portalon cave at Sierra de Atapuerca, Spain. We show that these individuals emerged from the same ancestral gene pool as early farmers in other parts of Europe, suggesting that migration was the dominant mode of transferring farming practices throughout western Eurasia. In contrast to central and northern early European farmers, the Chalcolithic El Portalon individuals additionally mixed with local southwestern hunter-gatherers. The proportion of hunter-gatherer-related admixture into early farmers also increased over the course of two millennia. The Chalcolithic El Portalon individuals showed greatest genetic affinity to modern-day Basques, who have long been considered linguistic and genetic isolates linked to the Mesolithic whereas all other European early farmers show greater genetic similarity to modern-day Sardinians. These genetic links suggest that Basques and their language may be linked with the spread of agriculture during the Neolithic. Furthermore, all modern-day Iberian groups except the Basques display distinct admixture with Caucasus/Central Asian and North African groups, possibly related to historical migration events. The El Portalon genomes uncover important pieces of the demographic history of Iberia and Europe and reveal how prehistoric groups relate to modern-day people.
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