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| 10. |
- Holmberg, Carl Jacob, et al.
(författare)
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The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
- 2022
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Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
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- Liu, RN, et al.
(författare)
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HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 5093-
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Tidskriftsartikel (refereegranskat)abstract
- The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection withM. tuberculosisisn’t well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection withM. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant forM. tuberculosiscontrol.Vhl cKOmice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility toM. tuberculosisinfection and the impaired responses ofVhl-deficient T cells are HIF-1-dependent.
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- Borgenvik, Anna, 1987-, et al.
(författare)
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Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma
- 2022
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 82:24, s. 4586-4603
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Tidskriftsartikel (refereegranskat)abstract
- Relapse is the leading cause of death in patients with medulloblas-toma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.Significance: SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.
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| 18. |
- Fagher, K., et al.
(författare)
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Preparing for snow-sport events at the Paralympic Games in Beijing in 2022 : recommendations and remaining questions
- 2022
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Ingår i: BMJ Open Sport & Exercise Medicine. - : BMJ. - 2055-7647. ; 8:1
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Forskningsöversikt (refereegranskat)abstract
- During the 2022 Winter Paralympic Games in Beijing, the Para snow-sport events will be held at high altitudes and in possibly cold conditions while also requiring adjustment to several time zones. Furthermore, the ongoing COVID-19 pandemic may lead to suboptimal preparations. Another concern is the high rate of injuries that have been reported in the Para alpine and snowboard events. In addition to these challenges, Para athletes various impairments may affect both sports-specific demands and athlete health. However, the group of Para snow-sport athletes is an understudied population. Accordingly, this perspective paper summarises current knowledge to consider when preparing for the Paralympic Games in Beijing and point out important unanswered questions. We here focus specifically on how sport-specific demands and impairment-related considerations are influenced by altitude acclimatisation, cold conditions, travel fatigue and jetlag, complications due to the COVID-19 pandemic, and injury prevention and sports safety considerations. As Para athletes with spinal cord injury, limb deficiency, cerebral palsy and visual impairment account for the majority of the Para snow-sport athletes, the focus is mainly on these impairment groups. In brief, we highlight the extra caution required to ensure athlete health, performance and sports safety among Para athletes participating in the snow-sport events in the 2022 Beijing Paralympic Games. Although there is an urgent need for more high-quality research focusing on Para winter athletes, we hope these non-consensus recommendations will help prepare for the 2022 Beijing Paralympic Winter Games.
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| 19. |
- Hagberg, Johan, 1973, et al.
(författare)
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Konsumtionsrapporten 2023
- 2023
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Rapport (populärvet., debatt m.m.)abstract
- I Konsumtionsrapporten 2023 sammanfattas och analyseras konsumtionen i Sverige under 2022. I den första delen, ”Hushållens konsumtion” ges en översikt över den privata konsumtionen i Sverige och hur den förändrats. Här beskrivs även skillnader mellan olika hushållstyper och konsumentgrupper, hållbarhetsaspekter på konsumtionen samt hushållens framtidsförväntningar på den egna ekonomin. I andra delen, ”Detaljhandeln” beskrivs försäljning och utveckling inom detaljhandeln under 2022 med fokus på olika delbranscher, kanaler och platser, inom e-handeln respektive den butiksbaserade detaljhandeln. Den andra delen avslutas med handelns framtidsförväntningar. Årets Konsumtionsrapport innehåller två fördjupningsdelar som var en och analyserar aktuella teman inom konsumtion. I den första av fördjupningsdelarna analyserar Emma Björner digitalisering inom turism, besöksnäring och upplevelseekonomi. I den andra fördjupningsdelen analyserar och diskuterar Benjamin Hartmann olika exempel på nostalgisk konsumtion.
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| 22. |
- Larsen, Filip J, 1977-, et al.
(författare)
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Mitochondrial oxygen affinity increases after sprint interval training and is related to the improvement in peak oxygen uptake.
- 2020
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 229:3
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The body responds to exercise training by profound adaptations throughout the cardiorespiratory and muscular systems, which may result in improvements in maximal oxygen consumption (VO2 peak) and mitochondrial capacity. By convenience, mitochondrial respiration is often measured at supra-physiological oxygen levels, an approach that ignores any potential regulatory role of mitochondrial affinity for oxygen (p50mito ) at physiological oxygen levels.METHODS: In this study, we examined the p50mito of mitochondria isolated from the Vastus lateralis and Triceps brachii in 12 healthy volunteers before and after a training intervention with 7 sessions of sprint interval training using both leg cycling and arm cranking. The changes in p50mito were compared to changes in whole-body VO2 peak.RESULTS: We here show that p50mito is similar in isolated mitochondria from the Vastus (40 ± 3.8 Pa) compared to Triceps (39 ± 3.3) but decreases (mitochondrial oxygen affinity increases) after 7 sessions of sprint interval training (to 26 ± 2.2 Pa in Vastus and 22 ± 2.7 Pa in Triceps, both p<0.01). The change in VO2 peak modeled from changes in p50mito was correlated to actual measured changes in VO2 peak (R2 =0.41, p=0.002).CONCLUSION: Together with mitochondrial respiratory capacity, p50mito is a critical factor when measuring mitochondrial function, it can decrease with sprint interval training and should be considered in the integrative analysis of the oxygen cascade from lung to mitochondria.
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| 23. |
- Nilsson, Magnus, et al.
(författare)
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Characterization of Selective and Potent JAK1 Inhibitors Intended for the Inhaled Treatment of Asthma
- 2022
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Ingår i: Drug Design, Development and Therapy. - : Informa Healthcare. - 1177-8881. ; 16, s. 2901-2917
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Janus kinase 1 (JAK1) is implicated in multiple inflammatory pathways that are critical for the pathogenesis of asthma, including the interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin cytokine signaling pathways, which have previously been targeted to treat allergic asthma. Here, we describe the development of AZD0449 and AZD4604, two novel and highly selective JAK1 inhibitors with promising properties for inhalation.Methods: The effects of AZD0449 and AZD4604 in JAK1 signaling pathways were assessed by measuring phosphorylation of signal transducer and activator of transcription (STAT) proteins and chemokine release using immunoassays of whole blood from healthy human volunteers and rats. Pharmacokinetic studies performed on rats evaluated AZD0449 at a lung deposited dose of 52 mu g/kg and AZD4604 at 30 mu g/kg. The efficacy of AZD0449 and AZD4604 was assessed by evaluating lung inflammation (cell count and cytokine levels) and the late asthmatic response (average enhanced pause [Penh]).Results: Both compounds inhibited JAK1-dependent cytokine signaling pathways in a dose-dependent manner in human and rat leukocytes. After intratracheal administration in rats, both compounds exhibited low systemic exposures and medium-to-long terminal lung half-lives (AZD0449, 34 hours; AZD4604, 5 hours). Both compounds inhibited STAT3 and STAT5 phosphorylation in lung tissue from ovalbumin (OVA)-challenged rats. AZD0449 and AZD4604 also inhibited eosinophilia in the lung and reduced the late asthmatic response, measured as Penh in the OVA rat model.Conclusion: AZD0449 and AZD4604 show potential as inhibitors of signaling pathways involved in asthmatic immune responses, with target engagement demonstrated locally in the lung. These findings support the clinical development of AZD0449 and AZD4604 for the treatment of patients with asthma.
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| 24. |
- Sánchez-Cano, Beatriz, et al.
(författare)
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Mars’ plasma system. Scientific potential of coordinated multipoint missions : "The next generation"
- 2022
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Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 54, s. 641-676
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this White Paper, submitted to ESA’s Voyage 2050 call, is to get a more holistic knowledge of the dynamics of the Martian plasma system, from its surface up to the undisturbed solar wind outside of the induced magnetosphere. This can only be achieved with coordinated multi-point observations with high temporal resolution as they have the scientific potential to track the whole dynamics of the system (from small to large scales), and they constitute the next generation of the exploration of Mars analogous to what happened at Earth a few decades ago. This White Paper discusses the key science questions that are still open at Mars and how they could be addressed with coordinated multipoint missions. The main science questions are: (i) How does solar wind driving impact the dynamics of the magnetosphere and ionosphere? (ii) What is the structure and nature of the tail of Mars’ magnetosphere at all scales? (iii) How does the lower atmosphere couple to the upper atmosphere? (iv) Why should we have a permanent in-situ Space Weather monitor at Mars? Each science question is devoted to a specific plasma region, and includes several specific scientific objectives to study in the coming decades. In addition, two mission concepts are also proposed based on coordinated multi-point science from a constellation of orbiting and ground-based platforms, which focus on understanding and solving the current science gaps.
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| 25. |
- Stenmark Tullberg, Axel, et al.
(författare)
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Immune infiltrate in the primary tumor predicts effect of adjuvant radiotherapy in breast cancer; results from the randomized SweBCG91RT trial.
- 2021
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 27:3, s. 749-758
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-infiltrating immune cells play a key role in tumor progression. The purpose of this study was to analyze if the immune infiltrate predicts benefit from postoperative radiotherapy (RT) in a large randomized breast cancer RT trial.In the SweBCG91RT trial, patients with stage I and II breast cancer were randomized to breast conserving surgery (BCS) and postoperative RT or to BCS only and followed for a median time of 15.2 years. The primary tumor immune infiltrate was quantified through two independent methods; immunohistochemistry (IHC) and gene expression profiling. For IHC analyses, the absolute stromal area occupied by CD8+ T cells and FOXP3+ T cells, respectively, was used to define the immune infiltrate. For gene expression analyses, immune cells found to be prognostic in independent datasets were pooled into two groups consisting of antitumoral- and protumoral immune cells, respectively.An antitumoral immune response in the primary tumor was associated with a reduced risk of breast cancer recurrence and predicted less benefit from adjuvant RT. The interaction between RT and immune phenotype was significant for any recurrence in both the IHC and gene expression analyses (p=0.039 and p=0.035) and was also significant for IBTR in the gene expression analyses (p=0.025).Patients with an antitumoral immune infiltrate in the primary tumor have a reduced risk of any recurrence and may derive less benefit from adjuvant RT. These results may impact decisions regarding postoperative RT in early breast cancer.
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| 29. |
- Weishaupt, Holger, et al.
(författare)
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Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas
- 2023
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 25:1, s. 97-107
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Tidskriftsartikel (refereegranskat)abstract
- Background Malignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site. Methods Here we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next-generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies. Results A large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency on orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance. Conclusions Altogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis.
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| 30. |
- Adnan, Ali, et al.
(författare)
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Health-related quality of life among tonsillar carcinoma patients in Sweden in relation to treatment and comparison with quality of life among the population
- 2020
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 42:5, s. 860-872
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Tidskriftsartikel (refereegranskat)abstract
- Background The health-related quality of life (HRQOL) of tonsillar carcinoma survivors was explored to investigate any HRQOL differences associated with tumor stage and treatment. The survivors' HRQOL was also compared to reference scores from the population. Methods In this exploratory cross-sectional study patients were invited 15 months after their diagnosis and asked to answer two quality of life questionnaires (EORTC QLQ- C30, EORTC QLQ- HN35), 405 participated. Results HRQOL was associated with gender, with males scoring better than females on a few scales. Patients' HRQOL was more associated with treatment than tumor stage. Patients' HRQOL was worse than that in an age- and sex-matched reference group from the normal population, the largest differences were found for problems with dry mouth followed by problems with sticky saliva, senses, swallowing and appetite loss. Conclusions The tonsillar carcinoma patients had a worse HRQOL compared to the general population one year after treatment.
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| 31. |
- Ahlberg, M., et al.
(författare)
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Time without PSA recurrence after radical prostatectomy as a predictor of prostate cancer death
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:Suppl. 1, s. S286-S286
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction & Objectives: Although surveillance after radical prostatectomy routinely includes repeated Prostate Specific Antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk for prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence 5 and 10 years after radical prostatectomy.Materials & Methods: Between 1989 and 1998, 14 urological centres in Scandinavia randomized patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial. Data was collected prospectively. All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible in our cohort. 4 patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3). We stratified by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3), and negative or positive surgical margins. We analysed the cumulative incidences and absolute differences in metastatic disease and prostate cancer death.Results: We analysed 302 patients with complete follow-up during a median of 18 years. Median preoperative PSA was 9.8 ng/ml and median age at inclusion was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12% respectively. The long-term probabilities were higher for pT≥3 vs. pT2 and for positive vs. negative surgical margins.Conclusions: Following radical prostatectomy, patients with Gleason score ≤3+4=7 without biochemical recurrence 5 years after radical prostatectomy had low risk of metastases and prostate cancer death independent of pT-stage and surgical margins. The risk of clinical progression decreased drastically the first 3 years after radical prostatectomy and after 10 years without biochemical recurrence, no patient was diagnosed with metastases or died from prostate cancer. Our study indicates that men with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy can stop follow-up earlier than 10 years after radical prostatectomy while men with adverse pathology should continue with at least 10 years follow-up
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| 34. |
- Appelbom, S, et al.
(författare)
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The Rapid Implementation of a Psychological Support Model for Frontline Healthcare Workers During the COVID-19 Pandemic: A Case Study and Process Evaluation
- 2021
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 713251-
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic highlighted the need for psychological support initiatives directed toward frontline healthcare workers, which can be rapidly and sustainably implemented during an infectious disease outbreak. The current case study presents a comprehensive model of psychological support that was implemented at an intensive care unit (ICU) during the first wave of the COVID-19 pandemic. The psychological support model aimed at promoting a resilient stress reaction among frontline staff by protecting physical, social, and psychological resources. The initiatives, targeting different groups of workers, included education and training, peer support, psychologist-supervised and unsupervised group sessions, on-boarding for transferred staff, manager support, and individual sessions for workers experiencing strong stress reactions. The results of the process evaluation of this rapid implementation suggest that peer support initiatives as well as daily group sessions were the most appreciated forms of psychological support. Psychologists involved in organizing and providing the support highlighted several aspects of a successful implementation of the support model: offering support during work hours (preferably after shift), positive attitude of line managers that framed support initiatives as a team effort, and involvement of experienced psychologists able to quickly adjust the content of the support according to the current needs. The study also identified two main problems of the current implementation: the lack of efficient planning due to the use of volunteer work and the need for more structural resources on the organizational level to ensure long-term sustainability of the support model and its implementation among all groups of healthcare staff. The current case study highlights the importance of establishing permanent structural resources and routines for psychological support integrated in clinical practice by healthcare organizations to improve both rapid and sustainable response to future crises.
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| 35. |
- Beckmann, Kerri, et al.
(författare)
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Spironolactone use is associated with lower prostate cancer risk : a population-wide case-control study
- 2020
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Ingår i: Prostate Cancer and Prostatic Diseases. - : NATURE PUBLISHING GROUP. - 1365-7852 .- 1476-5608. ; 23:3, s. 527-533
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Tidskriftsartikel (refereegranskat)abstract
- Background Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties. Methods A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides. Results Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings. Conclusion PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.
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| 36. |
- Bedoya-Reina, O. C., et al.
(författare)
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Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome. Childhood neuroblastoma can be separated into high and low risk groups, with prognosis depending on age at diagnosis. Here, the authors show that low and high risk neuroblastoma tumours are composed of different cell types with different malignancy potential.
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| 37. |
- Berg, Malin, 1976, et al.
(författare)
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A national study of health-related quality of life in patients with cancer of the base of the tongue compared to the general population and to patients with tonsillar carcinoma
- 2021
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 43:12, s. 3843-3856
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Tidskriftsartikel (refereegranskat)abstract
- Background This exploratory, registry-based, cross-sectional study aimed to evaluate patients' health-related quality of life (HRQOL) in a subsite of oropharyngeal cancer: cancer of the base of the tongue (CBT). Methods CBT patients, treated with curative intent, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 15 months after diagnosis. The HRQOL of CBT patients was compared to reference scores from the general population and to that of tonsillar carcinoma patients. Results The 190 CBT patients scored significantly worse than members of the general population on most scales. CBT patients with human papilloma virus (HPV)-positive tumors had significantly better HRQOL on 8 of 28 scales than HPV-negative patients. Compared to 405 tonsillar carcinoma patients, CBT patients had significantly worse HRQOL on 8 of the 28 scales, the majority local head and neck related problems. Conclusion One year after treatment, CBT patients' HRQOL was significantly worse in many areas compared to that of the general population and slightly worse than that of tonsillar carcinoma patients.
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| 38. |
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| 39. |
- Buli-Holmberg, J., et al.
(författare)
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From the idea of inclusion into practice in the Nordic countries: a qualitative literature review
- 2023
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Ingår i: European Journal of Special Needs Education. - : Informa UK Limited. - 0885-6257 .- 1469-591X. ; 38:1, s. 79-94
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Forskningsöversikt (refereegranskat)abstract
- The qualitative literature review includes 34 articles published in English-language, peer-reviewed journals to obtain a Nordic perspective on the status of the research on how the idea of inclusion implemented into practice is reflected in the literature from 2009 through 2019. Qualitative content analysis was conducted. In the analysis, we identified the characteristics of the studies, how inclusion and inclusive education were defined, and which themes concerning the idea of inclusion into practice that emerged from the review. Articles from five Nordic countries were found, Sweden with most of the publications. Almost twice as many of the sampled articles used qualitative methods as quantitative. Inclusion and inclusive education were seldom defined explicit, and the different way of understanding inclusion that emerges was human rights and democratic principles, placement of SEN-students, participation and belongingness, and high-quality learning for all students. Three themes was highlighted in the transformation of the idea into practice: Placement and the organisation of schooling, Teachers' beliefs and attitudes, and Students' and parents' experiences. This literature review shows that few research studies have focused specific on how to transform the idea of inclusion into practice.
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| 40. |
- Burkard, T, et al.
(författare)
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THE ASSOCIATION BETWEEN BARIATRIC SURGERY AND DUPUYTREN DISEASE: A COHORT STUDY FROM SWEDISH NATIONWIDE HEALTHCARE REGISTRIES
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 974-975
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Dupuytren disease (DD) is multifactorial, with several genetic and environmental risk factors contributing to disease susceptibility. High body mass index, however, was suggested to be protective of DD.1 The impact of weight loss among obese patients on DD has not been assessed to date.Objectives:To assess the association between bariatric surgery and DD in a secondary care setting.Methods:We performed a propensity score (PS)-matched cohort study using data from Swedish nationwide healthcare registries (patient registry [secondary care], causes of death registry, prescribed drug registry). Patients aged 30-79 years who underwent bariatric surgery between 2006 and 2019 were matched to up to 2 obese bariatric surgery-free patients (called unexposed patients) based on their PS. PS-matching was carried out in risk set sampling to reduce selection bias, within 4 sequential cohort entry blocks to account for time trend biases. The outcome DD was defined as a diagnosis of DD in secondary care or partial or total fasciotomy of wrist or hand. After a 1-year run-in period, patients were followed in an “as-treated” approach. We applied Cox proportional hazard regression to calculate hazard ratios (HR) with 95% confidence intervals (CIs) of incident DD among bariatric surgery patients when compared to obese unexposed patients overall, and in subgroups of age, sex, bariatric surgery type, and by duration of follow-up.Results:A total of 34 959 bariatric surgery patients were PS-matched to 54 769 obese unexposed patients. A total of 71.6% of bariatric surgery patients were women. Bariatric surgery patients had a mean age of 45.5 years and a mean follow-up of 6.9 years. All patient characteristics in obese unexposed patients were highly similar. We observed 126 and 136 severe DD cases among bariatric surgery and obese unexposed patients, respectively. The risk of DD was significantly increased in bariatric surgery patients compared to obese unexposed patients (HR = 1.30, 95% CI 1.02-1.65). The risk of DD was higher in women (HR = 1.36, 95% CI 1.00-1.84) than in men (HR = 1.05, 95% CI 0.70-1.58). Age did not modify the risk of DD among bariatric surgery patients compared to obese unexposed patients. Malabsorptive bariatric surgery yielded an increased risk of DD when compared to obese unexposed patients (HR = 1.33, 95% CI 1.04-1.71), while restrictive bariatric surgery yielded a null result. The risk of DD increased with duration of follow-up (>5 years of follow-up: HR = 1.63, 95% CI 1.14-2.34, null result in earlier follow-up).Conclusion:Our results suggest that substantial weight loss is associated with a latent increased risk of severe DD in an obese population. This observation further strengthens current evidence that high body mass index is protective against DD. The latency of risk increase of DD after bariatric surgery may suggest that slowly adapting metabolic changes may be part of the mechanism of DD emergence.References:[1]Hacquebord JH, Chiu VY, Harness NG. The Risk of Dupuytren Surgery in Obese Individuals. J Hand Surg Am. 2017, 42: 149–55.Acknowledgements:We thank Prof. Dr. Jesper Lagergren (Karolinksa Institutet, Stockholm, Sweden) for hosting Dr. Theresa Burkard for a research stay at the Upper Gastrointestinal Surgery Group and making the data available for use. Furthermore, we thank Dr. Giola Santoni (Karolinksa Institutet, Stockholm, Sweden) for her technical support.Disclosure of Interests:None declared
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| 41. |
- Colas, Kilian, et al.
(författare)
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Indolylbenzothiadiazoles as highly tunable fluorophores for imaging lipid droplet accumulation in astrocytes and glioblastoma cells
- 2021
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 11:39, s. 23960-23967
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Tidskriftsartikel (refereegranskat)abstract
- We present an extensive photophysical study of a series of fluorescent indolylbenzothiadiazole derivatives and their ability to specifically image lipid droplets in astrocytes and glioblastoma cells. All compounds in the series displayed positive solvatochromism together with large Stokes shifts, and π-extended derivatives exhibited elevated brightness. It was shown that the fluorescence properties were highly tunable by varying the electronic character or size of the N-substituent on the indole motif. Three compounds proved capable as probes for detecting small quantities of lipid deposits in healthy and cancerous brain cells. In addition, all twelve compounds in the series were predicted to cross the blood–brain barrier, which raises the prospect for future in vivo studies for exploring the role of lipid droplets in the central nervous system.
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| 42. |
- Dahm-Kähler, Pernilla, 1964, et al.
(författare)
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Implementation of National Guidelines increased survival in advanced ovarian cancer-A population-based nationwide SweGCG study
- 2021
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 161:1, s. 244-250
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Tidskriftsartikel (refereegranskat)abstract
- Aim. The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation. Method. Women with primary epithelial ovarian cancer, FIGO stage IIIC?IV, registered in the Swedish Quality Registry for Gynecologic Cancer 2008?2011 and 2013?2016 were included. Surgical outcomes were analyzed, including frequency of complete cytoreduction (R0). Relative survival (RS) and excess mortality rate ratios (EMRRs) were computed as measures of survival. Univariable and multivariable regression (Poisson) were calculated. Results. In total, 3728 women were identified, 1746 before and 1982 after NGOC. After adjusting for age and stage, survival was improved 2013?2016 vs. 2008?2011 (EMRR 0.89; 95%CI:0.82?0.96, p < 0.05). For women undergoing primary debulking surgery (PDS), R0 frequency (28.9% vs. 53.3%; p < 0.001) and 5-year RS (29.6% (95% CI:26.8?32.8) vs. 37.4% (95%CI:33.6?41.7)) were increased, but fewer patients (58% vs. 44%, p < 0.001) underwent PDS after NGOC implementation. Median survival for the PDS cohort increased from 35 months (95%CI,32.8?39.2) to 43 months (95%CI,40.9?46.4). In the neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) cohort, R0 increased (36.8% to 50.1%, p < 0.001), but not 5-year RS (17.5% vs. 20.7%,ns). Compared to PDS, the EMRR was 1.32 (95%CI,1.19 & ndash;1.47, p < 0.001) for NACT+IDS and 3.00 (95% CI,2.66 & ndash;3.38, p < 0.001) for chemotherapy alone. In multivariable analyses, PDS, R0, age <= 70 years, and stage IIIC were found to be independent factors for improved RS. Conclusion. Implementation of the first National Guidelines for Ovarian Cancer improved relative survival in advanced ovarian cancer. (c) 2021 Published by Elsevier Inc.
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| 43. |
- Doloczki, Susanne, et al.
(författare)
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An Indolin-3-imine Photobase and pH Sensitive Fluorophore
- 2023
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Ingår i: ChemPhotoChem. - : John Wiley & Sons. - 2367-0932.
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Tidskriftsartikel (refereegranskat)abstract
- This work presents the pH sensing ability of a fluorescent indolin-3-imine derivative. Protonation of the weakly basic imine (pKa = 8.3 of its conjugate acid) results in a significant redshift of the absorption band. The fluorophore acts as a photobase, with a basicity increase of approximately 6 units upon photoexcitation. This behavior promotes excited state proton transfer from weak acids such as protic solvents. The characteristics of the fluorophore enable sensing of water fractions in organic solvents and differentiation between methanol, ethanol, and longer chain alcohols. Initial cell studies indicated the future potential of indolin-3-imines as fluorophores for bioimaging applications.
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| 44. |
- Doloczki, Susanne, et al.
(författare)
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Photoinduced ring‐opening and phototoxicity of an indolin‐3‐one derivative
- 2023
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Ingår i: Chemistry - A European Journal. - : John Wiley & Sons. - 0947-6539 .- 1521-3765. ; 29:51
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Tidskriftsartikel (refereegranskat)abstract
- The study of a fluorescent indolin-3-one derivative is reported that, as opposed to its previously described congeners, selectively undergoes photoactivated ring-opening in apolar solvents. The excited state involved in this photoisomerization was partially deactivated by the formation of singlet oxygen. Cell studies revealed lipid droplet accumulation and efficient light-induced cytotoxicity.
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| 45. |
- Doloczki, Susanne, et al.
(författare)
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Photophysical characterization and fluorescence cell imaging applications of 4-N-substituted benzothiadiazoles
- 2022
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 12:23, s. 14544-14550
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Tidskriftsartikel (refereegranskat)abstract
- In this work, a series of fluorescent 2,1,3-benzothiadiazole derivatives with various N-substituents in the 4- position was synthesized and photophysically characterized in various solvents. Three compounds emerged as excellent fluorescent probes for imaging lipid droplets in cancer cells. A correlation between their high lipophilicity and lipid droplet specificity could be found, with log P ≥ 4 being characteristic for lipid droplet accumulation.
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| 46. |
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| 47. |
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| 48. |
- Forsberg, A., et al.
(författare)
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Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:6, s. 513-521
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Tidskriftsartikel (refereegranskat)abstract
- Background Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. Methods We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with Clinical Trials.gov, NCT02078804. Findings Between March 1, 2014, and Dec 31, 2020, 278 280 people were induded in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35.1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55.5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0.16%) of 31140 people in the colonoscopy group versus 121 (0. 20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0.78, 95% CI 0.56-1.09). Advanced adenomas were detected in 637 (2.05%) people in the colonoscopy group and 968 (1.61%) in the faecal immunochemical test group (RR 1.27, 95% CI 1.15-1.41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. Interpretation The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 49. |
- Grinin, V. P., et al.
(författare)
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Modelling UX Ori star eclipses based on spectral observations with the Nordic Optical Telescope - I. RR Tau
- 2023
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 524:3, s. 4047-4061
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Tidskriftsartikel (refereegranskat)abstract
- Based on observations obtained with the Nordic Optical Telescope (NOT) we investigate the spectral variability of the Herbig Ae star RR Tau. This star belongs to the UX Ori family, characterized by very deep fadings caused by the screening of the star with opaque fragments (clouds) of the protoplanetary discs. At the moments of such minima one observes strong spectral variability due to the fact that the dust cloud occults, for an observer, not only the star but also a part of the region where the emission spectrum originates. We calculated a series of obscuration models to interpret the observed variability of the H a line parameters. We consider two main obscuration scenarios: (1) the dust screen rises vertically above the circumstellar disc, and (2) the screen intersects the line-of-sight moving azimuthally with the disc. In both cases, the model of the emission region consists of a compact magnetosphere and a magnetocentrifugal disc wind. Comparison with observations shows that the first scenario explains well the variability of the radiation flux, the equivalent width, as well as the asymmetry of the H a line during eclipses, while the second scenario explains them only partly. This permits us to suggest that in the case of RR Tau, the main causes of the eclipses are either a structured disc wind, or the charged dust lifted along the field lines of the poloidal component of the magnetic field of the circumstellar disc.
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| 50. |
- Hadid, L. Z., et al.
(författare)
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Ambipolar electrostatic field in negatively charged dusty plasma
- 2022
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Ingår i: Journal of Plasma Physics. - : Cambridge University Press. - 0022-3778 .- 1469-7807. ; 88:2
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Tidskriftsartikel (refereegranskat)abstract
- We study the effect of negatively charged dust on the magnetic-field-aligned polarisation electrostatic field (E-parallel to) using Cassini's RPWS/LP in situ measurements during the `ring-grazing' orbits. We derive a general expression for E-parallel to and estimate for the first time in situ parallel to E-parallel to parallel to (approximately 10(-5) V m(-1)) near the Janus and Epimetheus rings. We further demonstrate that the presence of the negatively charged dust close to the ring plane (vertical bar Z vertical bar less than or similar to 0.11 R-s) amplifies parallel to E-parallel to parallel to by at least one order of magnitude and reverses its direction due to the effect of the charged dust gravitational and inertial forces. Such reversal confines the electrons at the magnetic equator within the dusty region, around 0.047 R-s above the ring plane. Furthermore, we discuss the role of the collision terms, in particular the ion-dust drag force, in amplifying E-parallel to. These results imply that the charged dust, as small as nanometres in size, can have a significant influence on the plasma transport, in particular ambipolar diffusion along the magnetic field lines, and so their presence must be taken into account when studying such dynamical processes.
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