| 1. |
- Fransson, Per, et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC) : patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial.METHODS: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321.FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41).INTERPRETATION: Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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| 2. |
- Liljegren, Lars, 1966-
(författare)
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The Taming of a Viking : August Strindberg, Translation and Post-Victorian Censorship
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation studies August Strindberg’s two-volume collection of short stories, Giftas (1884, 1886) and its first English translation, Ellie Schleussner’s Married (1913). The purpose is to demonstrate that Married deviates from the original in many ways, primarily on the very aspects that were generally associated with the work. The study also analyses and discusses possible influences on the translation outcome and its reception.The dissertation makes clear how the traditional image of Strindberg as a provocative author and a persuasive debater has almost disappeared in Married due to culturally motivated translational choices and the need to avoid state censorship, which could also explain the weak reception of Married. The hypothesis is that British readers were disappointed as Strindberg did not live up to the image they had expected to find. As there was state censorship of “obscene” publications in both Britain and the USA at the time Married was published, other Strindberg works saw similar changes in English translation. The conclusion is that a combination of these phenomena may help explain Strindberg’s relatively belated entry into the Anglo-American canon.The dissertation is carried out within the frames of translation studies, which is characterized by being multidisciplinary. The theoretical frame is based on descriptive translation studies (Gideon Toury) and polysystem theory (Itamar Even-Zohar), but it also incorporates perspectives from reception theory, the notion of multiple translatorship and imagology. Thus, it has both a source- and target-oriented focus. Of special relevance to the thesis are also the concepts of habitus, borrowed from the sociologist Pierre Bourdieu, and the panopticon effect, as described by Michel Foucault.Through some key concepts and perspectives borrowed from actor-network theory, the study shows how a prerequisite for a successful transfer of Scandinavian works at this time was easy access for the authors or literary agents of the source culture to a network of cultural agents such as translators, publishers, theatre directors and critics. The study analyses how Strindberg’s access to such networks in France and Germany and his lack of a similar network in Britain and the USA may explain the divergent reception in these countries. In addition, the dissertation portrays the conditions for how European literature in general could migrate within Europe at the turn of the 20th century, and how the social norms in Britain and the USA in particular have affected the translation of Strindberg’s works.
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| 3. |
- Nyqvist, Johanna, et al.
(författare)
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Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up
- 2016
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 118:2, s. 335-341
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. Material and methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, NO glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.
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| 4. |
- Widmark, Anders, et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer : 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 394:10196, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RTPC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation.Methods: In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) or conventional fractionated radiotherapy (78.0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1.338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321.Findings: Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5.0 years (IQR 3.1-7.0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1.002 (95% CI 0.758-1.325; log-rank p=0.99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0.057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0.0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1.00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0.14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity.Interpretation: Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 5. |
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| 6. |
- Zackrisson, Björn, et al.
(författare)
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Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN trial
- 2015
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 117:1, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: This report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal cancers. Material and methods: Patients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1-2, NO glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1 Gy + 2 Gy per day, 5 days/week for 4.5 weeks, total dose 68 Gy) and conventional fractionation (CF) (2 Gy per day, 5 days/week for 7 weeks, total dose 68 Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. Results: There was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p = 0.75). LRC at 5 years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms (p = 0.99). The estimated cancer specific survival (CSS) at 5 years was 62.2% (AF) and 63.3% (CF) (p = 0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16 tumours. Conclusion: This update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect.
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| 7. |
- Zackrisson, Björn, et al.
(författare)
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Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN study
- 2011
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Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 100:1, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Studies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF. Materials and methods: Patients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1-T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. RESULTS: The study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III-IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p=0.07) and for large tumours (T3-T4) (p=0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects. Conclusion: Overall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated.
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| 8. |
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| 9. |
- Andersson, Lars Gustaf, et al.
(författare)
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Litteratur och film
- 2021
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Ingår i: Natur & Kulturs Litteraturhistoria. - 9789127149403 ; , s. 658-668
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Bokkapitel (refereegranskat)abstract
- Brief account of the relationship between film and literature as art form, commodity, technology and cultural phenomenon.
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| 10. |
- Atteia, A., et al.
(författare)
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Structure, organization and expression of the genes encoding mitochondrial cytochrome c1 and the Rieske iron-sulfur protein in Chlamydomonas reinhardtii
- 2003
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Ingår i: Molecular Genetics and Genomics. - : Springer Verlag. - 1617-4615 .- 1617-4623. ; 268:5, s. 637-644
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Tidskriftsartikel (refereegranskat)abstract
- The sequence and organization of the Chlamydomonas reinhardtii genes encoding cytochrome c 1 ( Cyc1) and the Rieske-type iron-sulfur protein ( Isp), two key nucleus-encoded subunits of the mitochondrial cytochrome bc 1 complex, are presented. Southern hybridization analysis indicates that both Cyc1 and Isp are present as single-copy genes in C. reinhardtii. The Cyc1 gene spans 6404 bp and contains six introns, ranging from 178 to 1134 bp in size. The Isp gene spans 1238 bp and contains four smaller introns, ranging in length from 83 to 167 bp. In both genes, the intron/exon junctions follow the GT/AG rule. Internal conserved sequences were identified in only some of the introns in the Cyc1 gene. The levels of expression of Isp and Cyc1 genes are comparable in wild-type C. reinhardtii cells and in a mutant strain carrying a deletion in the mitochondrial gene for cytochrome b (dum-1). Nevertheless, no accumulation of the nucleus-encoded cytochrome c 1 or of core proteins I and II was observed in the membranes of the respiratory mutant. These data show that, in the green alga C. reinhardtii, the subunits of the cytochrome bc1 complex fail to assemble properly in the absence of cytochrome b.
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| 11. |
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| 12. |
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| 13. |
- Betzholtz, Per-Eric, et al.
(författare)
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With that diet, you will go far : trait-based analysis reveals a link between rapid range expansion and a nitrogen-favoured diet
- 2013
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 280:1750, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Recent global change has had a substantial influence on the distribution of organisms, and many species are currently expanding their ranges. To evaluate the underlying processes, long-term data with good geographic resolution are essential. One important but generally overlooked data source is offered by the taxon-specific national catalogues of first provincial records that are kept in many countries. Here, we use such data to quantify trait-based influences on range expansion in Swedish butterflies and moths between 1973 and 2010. Of 282 species meeting pre-defined quality criteria, 170 expanded their northern range margin, with a mean expansion rate of 2.7 km per year. The analyses demonstrate that habitat and diet generalists, forest species and species active during warm conditions have expanded their ranges more rapidly than other species. Notably, range expansion in diet specialists was positively related to a nitrogen-favoured larval diet, an effect not found among oligo- or polyphagous species. In contrast to the general view, this shows that specialist species can undergo rapid range expansion. We suggest that increased areas of nitrogen-rich habitat, and increased availability of a nitrogen-favoured diet, are among the most important drivers of range expansions, potentially having far-reaching consequences for a wide variety of organisms.
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| 14. |
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| 15. |
- Björk, Staffan, et al.
(författare)
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WEST: A Web Browser for Small Terminals
- 1999. - 1
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Konferensbidrag (refereegranskat)abstract
- We describe WEST, a WEb browser for Small Terminals, that aims to solve some of the problems associated with accessing web pages on hand-held devices. Through a novel combination of text reduction and focus+context visualization, users can access web pages from a very limited display environment, since the system will provide an overview of the contents of a web page even when it is too large to be displayed in its entirety. To make maximum use of the limited resources available on a typical hand-held terminal, much of the most demanding work is done by a proxy server, allowing the terminal to concentrate on the task of providing responsive user interaction. The system makes use of some interaction concepts reminiscent of those defined in the Wireless Application Protocol (WAP), making it possible to utilize the techniques described here for WAP-compliant devices and services that may become available in the near future.
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| 16. |
- Bohlin, Jan
(författare)
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Enzymes and electron transport in microbial chlorate respiration
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microbial chlorate respiration plays an important role in the turnover of oxochlorates in nature and industrial waste management. This thesis deals with the characterization of the molecular components of chlorate respiration in Ideonella dechloratans. Chlorate respiration utilizes two soluble periplasmic enzymes, chlorate reductase and chlorite dismutase, to convert chlorate to chloride and oxygen. The genes encoding the enzymes participating in the chlorate degradation have been sequenced, and are found in close proximity, forming a gene cluster for chlorate metabolism. This work also includes the successful recombinant expression of three genes from Ideonella dechloratans. Two of the gene products, chlorite dismutase and the C subunit of chlorate reductase, participate in the chlorate respiration. The third gene, which is found close to the gene cluster for chlorate metabolism, encodes a soluble c-type cytochrome. The localization of the gene suggests the corresponding protein as a candidate for a role as electron donor to chlorate reductase. Also, the role of soluble periplasmic c cytochromes of Ideonella dechloratans in chlorate respiration was studied. At least one of the soluble c cytochromes was found capable of serving as electron donor for chlorate reduction. This c cytochrome, and several others, can also donate electrons to a terminal oxidase for subsequent reduction of oxygen, as required for the branched electron flow during chlorate respiration.
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| 17. |
- Bonnier, Gaga, et al.
(författare)
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Kirunas Framtid - Kan man flytta en stad? : restaureringskonst på sin spets
- 2010
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Rapport (populärvet., debatt m.m.)abstract
- Ar 2004 konstaterade gruvbolaget LKAB att en på världsmarknaden ökad efterfrågan på järnmalm innebär att marken ovanför brytningsområdet i Kiruna spricker i takt med att malmen bryts. Detta deformationsområde kommer att omfatta större delen av den gamla staden inklusive kyrkan och stadshuset. Osäkerheten är stor om hur man skall gå till väga och de konkreta frågorna är ännu obesvarade. Diskussionen handlar om vart man skall flytta och den pendlar mellan ytterligheterna att helt avstå från det gamla och bygga helt nytt eller skapa ett nytt område med de gamla husen musealt återuppbyggda i ett landskapssammanhang som så långt möjligt påminner om det gamla. Den avgörande frågan är, menar vi, hur staden och dess invånare kan behålla sin identitet och sitt minne - framtiden för kulturmiljön i vidaste bemärkelse.Omvandlingen och den successiva flytten av Kirunas centrala delar är en av de riktigt stora samhällsbyggnads- och bevarandefrågorna i vår samtid, en samhällsförändring med global räckvidd - restaureringskonst på sin spets.
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| 18. |
- Borromei, Ana Maria, et al.
(författare)
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Multiproxy record of Holocene paleoenvironmental change, Tierra del Fuego, Argentina
- 2010
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - 0031-0182. ; 286:1-2, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- We interpret Holocene environmental conditions in a subantarctic high Andean valley from palynological and diatom analysis, peat stratigraphy, and local geomorphology. The multiproxy data from Las Cotorras mire (54° 41′ 13″ S; 68° 02′ 51″ W; 420 m a.s.l.) indicate the development of a soligenous mire, as a result of a fine grained tephra layer deposition over the mineral soils sometime prior to 8000 cal yr BP. The paleoecological conditions in the mire after 8000 cal yr BP show a rapid succession from a limnic to a telmatic stage as the mire is colonized by sedges (Cyperaceae) and herbaceous communities. The upland vegetation changed from cushion and shrub heaths to an expansion of Nothofagus forest at high altitudes after 6500 cal yr BP. The peat is interbedded with clastic sediment that originates from mass wasting events or floods. These depositional changes affected the mire ecosystem water-table level and nutrient status (oligotrophic and/or eutrophic conditions). Maxima in total pollen influx at about 2800, 1100 and 700 cal yr BP coincide with heightened mineral flux, and these changes are related to precipitation and slope processes. The major vegetational change registered in the pollen record is the decline of Nothofagus pollen after 1000 cal yr BP, which reaches a minimum between ca. 680 and 300 cal yr BP. This minimum was likely caused by cool, wet conditions that coincided with the Little Ice Age (LIA) in the Southern Hemisphere. Our results indicate the sensitivity of subantarctic Nothofagus forest and mire ecosystems to changes during the Holocene.
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| 19. |
- Brauner, Susanna, et al.
(författare)
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H1N1 vaccination in Sjogren's syndrome triggers polyclonal B cell activation and promotes autoantibody production
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:10, s. 1755-1763
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesVaccination of patients with rheumatic disease has been reported to result in lower antibody titres than in healthy individuals. However, studies primarily include patients on immunosuppressive therapy. Here, we investigated the immune response of treatment-naive patients diagnosed with primary Sjogren's syndrome (pSS) to an H1N1 influenza vaccine.Methods Patients with Sjogren's syndrome without immunomodulatory treatment and age-matched and gender-matched healthy controls were immunised with an H1N1 influenza vaccine and monitored for serological and cellular immune responses. Clinical symptoms were monitored with a standardised form. IgG class switch and plasma cell differentiation were induced in vitro in purified naive B cells of untreated and hydroxychloroquine-treated patients and healthy controls. Gene expression was assessed by NanoString technology.ResultsSurprisingly, treatment-naive patients with Sjogren's syndrome developed higher H1N1 IgG titres of greater avidity than healthy controls on vaccination. Notably, off-target B cells were also triggered resulting in increased anti-EBV and autoantibody titres. Endosomal toll-like receptor activation of naive B cells in vitro revealed a greater propensity of patient-derived cells to differentiate into plasmablasts and higher production of class switched IgG. The amplified plasma cell differentiation and class switch could be induced in cells from healthy donors by preincubation with type 1 interferon, but was abolished in hydroxychloroquine-treated patients and after in vitro exposure of naive B cells to chloroquine.ConclusionsThis comprehensive analysis of the immune response in autoimmune patients to exogenous stimulation identifies a mechanistic basis for the B cell hyperactivity in Sjogren's syndrome, and suggests that caution is warranted when considering vaccination in non-treated autoimmune patients.
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| 20. |
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| 21. |
- Brogren, Elisabeth, et al.
(författare)
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Striatal hand deformities in Parkinson's disease - hand surgical perspectives
- 2022
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Ingår i: Movement Disorders Clinical Practice. - : Wiley. - 2330-1619. ; 9:8, s. 1047-1054
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe knowledge about striatal hand deformities (SHD) in Parkinson’s disease (PD), has recently increased but need more attention due to their early impact on dexterity. The focus of clinical studies has been on the staging of SHD severity and neurological features. However, a hand surgical perspective has not been considered.ObjectivesOur purpose was to examine SHD in patients with PD using hand surgical assessmentmethods and the recommended staging of SHD.MethodsIn this observational study, a specialist in neurological physiotherapy examined 100 consecutive PD patients and identified 35 with suspected SHD, who were thenexamined by two hand surgeons. Their hands were clinically evaluated for severity of SHD, according to a previous proposed staging, focusing on metacarpophalangeal (MCP) joint flexion, presence of intrinsic and extrinsic tightness, as well as other hand deformities.ResultsThree kinds of deformities were identified among 35 included patients: surgicaldiagnoses unrelated to PD (n=5), SHD (n=23), and PD related hand deformities with increased extrinsic tightness (n=10); three of these 10 patients had also contralateral SHD, thus are included in SHD group. In addition to previously described MCP joint flexion, swan neck deformity and z-thumb deformity, we found in most hands finger “clefting”, abduction of the little finger and/or an increased intrinsic tightness, indicating pathology of intrinsic muscles of the hand involved in SHD.ConclusionsSHD diagnosed with a modified staging method, including features of intrinsic andextrinsic hand deformities, should be considered in PD to implement early and more accurate treatment
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| 22. |
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| 23. |
- Cardol, Pierre, et al.
(författare)
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Oxidative Phosphorylation : Building blocks and related components
- 2009
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Ingår i: The Chlamydomonas Sourcebook. - Oxford : Academic Press. - 0123708753 ; , s. 469-502
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter summarizes the knowledge of the oxidative phosphorylation (OXPHOS) constituents of Chlamydomonas and of the components involved in their biogenesis and addresses alternate dehydrogenases and oxidases which are particular to photosynthetic organisms, and several other mitochondrial components related to OXPHOS. Reference to the components of Polytomella sp., a colorless alga closely related to Chlamydomonas is clearly made. The main complexes involved in electron transport seem to share a similar number of subunits, and many of the algal polypeptides have plant homologues. Some differences are apparent, such as the presence of a fragmented COX2 subunit, which seems to be unique to chlorophyte algae. OXPHOS is defined as an electron transfer chain driven by substrate oxidation that is coupled to the synthesis of ATP through an electrochemical transmembrane gradient. The characterization of Arabidopsis mitochondrial components through proteomic approaches has advanced significantly. As a unicellular organism, Chlamydomonas offers the unique opportunity to study organelle-organelle interactions, particularly between mitochondria and chloroplasts. It has become evident that crosstalk between these organelles takes place, mainly through intracellular metabolite pools. © 2009 Elsevier Inc. All rights reserved.
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| 24. |
- Daşu, Alexandru, et al.
(författare)
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Secondary malignancies from prostate cancer radiation treatment : a risk analysis of the influence of target margins and fractionation patterns
- 2011
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 79:3, s. 738-746
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study explores the implications for cancer induction of treatment details such as fractionation, planning target volume (PTV) definition, and interpatient variations, which are relevant for the radiation treatment of prostate carcinomas.METHODS AND MATERIALS: Treatment planning data from 100 patients have been analyzed with a risk model based on the United Nations Scientific Committee on the Effects of Atomic Radiation competition model. The risk model can account for dose heterogeneity and fractionation effects characteristic for modern radiotherapy. Biologically relevant parameters from clinical and experimental data have been used with the model.RESULTS: The results suggested that changes in prescribed dose could lead to a modification of the risks for individual organs surrounding the clinical target volume (CTV) but that the total risk appears to be less affected by changes in the target dose. Larger differences are observed for modifications of the margins between the CTV and the PTV because these have direct impact onto the dose level and dose heterogeneity in the healthy tissues surrounding the CTV. Interpatient anatomic variations also have to be taken into consideration for studies of the risk for cancer induction from radiotherapy.CONCLUSIONS: The results have shown the complex interplay between the risk for secondary malignancies, the details of the treatment delivery, and the patient heterogeneity that may influence comparisons between the long-term effects of various treatment techniques. Nevertheless, absolute risk levels seem very small and comparable to mortality risks from surgical interventions, thus supporting the robustness of radiation therapy as a successful treatment modality for prostate carcinomas.
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| 25. |
- Dasu, Alexandru, et al.
(författare)
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The risk for secondary cancers in patients treated for prostate carcinoma – An analysis with the competition dose response model
- 2009
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Ingår i: IFMBE Proceedings. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1680-0737 .- 1433-9277. ; 25/III, s. 237-240
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Tidskriftsartikel (refereegranskat)abstract
- The risk for radiation-induced cancers has become increasingly important as patient survival following radiotherapy has increased due to the advent of new methods for early detection and advanced treatment. Attempts have been made to quantify the risk of cancer that may be associated with various treatment approaches, but the accuracy of predictions is rather low due to the influence of many confounding factors. It is the aim of this paper to investigate the impact of dose heterogeneity and inter-patient anatomical heterogeneity that may be encountered in a population of patients undergoing radiotherapy and are thought to influence risk predictions. Dose volume histograms from patients treated with radiation for the carcinoma of the prostate have been used to calculate the risk for secondary malignancies using a competition dose-response model previously developed. Biologically-relevant parameters derived from clinical and experimental data have been used for the model. The results suggested that dose heterogeneity plays an important role in predicting the risk for secondary cancer and that it should be taken into account through the use of dose volume histograms. Consequently, dose-response relationships derived for uniform relationships should be used with care to predict the risk for secondary malignancies in heterogeneously irradiated tissues. Inter-patient differences could lead to considerable uncertainties in the shape of the relationship between predicted risk and average tissue dose, as seen in epidemiological studies. They also lead to rather weak correlations between the risk for secondary malignancies and target volumes. The results stress the importance of taking into account the details of the clinical delivery of dose in radiotherapy for treatment plan evaluation or for retrospective analyses of the induction of secondary cancers. Nevertheless, the levels of risks are generally low and they could be regarded as the price of success for the advances in the radiotherapy of the prostate.
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