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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Poyatos, R., et al.
(författare)
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Global transpiration data from sap flow measurements: the SAPFLUXNET database
- 2021
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:6, s. 2607-2649
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Tidskriftsartikel (refereegranskat)abstract
- Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land-atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets, while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes. SAPFLUXNET version 0.1.5 is freely available from the Zenodo repository (https://doi.org/10.5281/zenodo.3971689; Poyatos et al., 2020a). The "sapfluxnetr" R package - designed to access, visualize, and process SAPFLUXNET data - is available from CRAN.
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- Nilsson, Magnus, et al.
(författare)
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Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed : The Study Protocol for the Randomized Controlled NEEDS Trial
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC.Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up.
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- Ekelin, M., et al.
(författare)
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Clinical supervisors’ experiences of midwifery students’ reflective writing : a process for mutual professional growth
- 2021
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Ingår i: Reflective Practice. - : Informa UK Limited. - 1462-3943 .- 1470-1103. ; 22:1, s. 101-114
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Tidskriftsartikel (refereegranskat)abstract
- Structured reflective writing during clinical placement has been shown to be valuable for students’ learning and for their personal and professional development. The aim of this study was to examine clinical supervisors’ experiences of midwifery students’ daily written reflections on their practice at birthing units. A qualitative study was performed, and data were analysed using content analysis. In total 17 midwives working as clinical supervisors in the South of Sweden were interviewed using both focus groups and individual interviews. One main category ‘A process for mutual professional growth’, three categories and seven subcategories emerged from the analyses. The supervisors’ experience was that reflective writing facilitated individualized supervision and initiated a loop of reflection. The way students wrote their reflections affected the feedback and was an aid for the supervisor to be active and flexible. The process of using written reflections was considered as a tool for following the progress of the students and the process of learning but also developed the midwife in her supervisory as well as in her professional role. The supervisors called for more time allotted, better organizational support, and clearer instructions for how to write feedback.
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- Kauppila, JH, et al.
(författare)
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Minimally invasive surgical techniques for oesophageal cancer and nutritional recovery: a prospective population-based cohort study
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e058763-
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Tidskriftsartikel (refereegranskat)abstract
- To explore whether the minimally invasive oesophagectomy (MIE) or hybrid minimally invasive oesophagectomy (HMIE) are associated with better nutritional status and less weight loss 1 year after surgery, compared with open oesophagectomy (OE).DesignProspective cohort study.SettingAll patients undergoing oesophagectomy for cancer in Sweden during 2013–2018.ParticipantsA total of 424 patients alive at 1 year after surgery were eligible, and 281 completed the 1-year assessment. Of these, 239 had complete clinical data and were included in the analysis.Primary and secondary outcome measuresThe primary outcome was nutritional status at 1 year after surgery, assessed using the abbreviated Patient-Generated Subjective Global Assessment questionnaire. The secondary outcomes included postoperative weight loss at 6 months and 1 year after surgery.ResultsOf the included patients, 78 underwent MIE, 74 HMIE while 87 patients underwent OE. The MIE group had the highest prevalence of malnutrition (42% vs 22% after HMIE vs 25% after OE), reduced food intake (63% vs 45% after HMIE vs 39% after OE), symptoms reducing food intake (60% vs 45% after HMIE vs 60% after OE) and abnormal activities/function (45% vs 32% after HMIE vs 43% after OE). After adjustment for confounders, MIE was associated with a statistically significant increased risk of reduced food intake 1 year after surgery (OR 2.87, 95% CI 1.47 to 5.61), compared with OE. Other outcomes were not statistically significantly different between the groups. No statistically significant associations were observed between surgical techniques and weight loss up to 1 year after surgery.ConclusionsMIE was statistically significantly associated with reduced food intake 1 year after surgery. However, no differences were observed in weight loss between the surgical techniques. Further studies on nutritional impact of surgical techniques in oesophageal cancer are needed.
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- Thies-Lagergren, Li, et al.
(författare)
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A Swedish register-based study exploring primary postpartum hemorrhage in 405 936 full term vaginal births between 2005 and 2015
- 2021
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Ingår i: European Journal of Obstetrics and Gynecologi. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 258, s. 184-188
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore diagnoses of postpartum haemorrhage following vaginal birth, in relation to socio-demographic and obstetrical data from women who gave birth at term, in Sweden, during the years 2005-2015. Study design: A register-based cohort study was carried out, describing and comparing socio-demographic variables, obstetric variables and infant variables in 52 367 cases of diagnosed postpartum haemorrhage compared to 353 569 controls without a postpartum haemorrhage diagnosis. Postpartum hemorrhage was identified in The Swedish Medical Birth Register by ICD-10 code O72. Variables for maternal characteristics were dichotomized and used to calculate odds ratios to find possible explanatory variables for postpartum haemorrhage. Results: Between 2005 and 2015 there was no statistically significant decrease in diagnoses of postpartum haemorrhage after vaginal birth at term. Primiparity was associated with the highest risk and women birthing their fifth or subsequent child were associated with the lowest risk of postpartum hemorrhage. Increased maternal age (> 35 years) and/or obesity (BMI > 30) were associated with higher odds of postpartum haemorrhage. The risk of postpartum hemorrhage was 55 % higher when vaginal birth followed induction as compared to vaginal birth after spontaneous onset. Some of the factors known to be associated with postpartum haemorrhage were poorly documented in The Swedish Medical Birth Register. Conclusions: Birthing women in a Swedish contemporary setting are, despite efforts to improve care, still at risk of birth being complicated by postpartum haemorrhage. Primiparity, increasing maternal age and/or obesity are found to provoke an increased risk and the reasons for these findings need to be further investigated. However, grand multi-parity did not increase the risk for postpartum hemorrhage. Codes for diagnoses require correct documentation in the birth records: only when local statistics are sound and correctly reported can intrapartum care be improved, and the incidence of postpartum haemorrhage reduced. (C) 2021 The Author(s). Published by Elsevier B.V.
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| 29. |
- van Leeuwen, Marieke, et al.
(författare)
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Phase III study of the European Organisation for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire
- 2023
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 17:4, s. 1111-1130
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales. Methods: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales. Results: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items. Conclusions: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study. Implications for Cancer Survivors: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors.
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- Zylstra, J, et al.
(författare)
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Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial
- 2022
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Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 56:7, s. 402-
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence for the use of exercise in cancer patients and data supporting enhanced tumour volume reduction following chemotherapy in animal models. To date, there is no reported histopathological evidence of a similar oncological benefit in oesophageal cancer.MethodsA prospective non-randomised trial compared a structured prehabilitation exercise intervention during neoadjuvant chemotherapy and surgery versus conventional best-practice for oesophageal cancer patients. Biochemical and body composition analyses were performed at multiple time points. Outcome measures included radiological and pathological markers of disease regression. Logistic regression calculated ORs with 95% CI for the likelihood of pathological response adjusting for chemotherapy regimen and chemotherapy delivery.ResultsComparison of the Intervention (n=21) and Control (n=19) groups indicated the Intervention group had higher rates of tumour regression (Mandard TRG 1–3 Intervention n=15/20 (75%) vs Control n=7/19 (36.8%) p=0.025) including adjusted analyses (OR 6.57; 95% CI 1.52 to 28.30). Combined tumour and node downstaging (Intervention n=9 (42.9%) vs Control n=3 (15.8%) p=0.089) and Fat Free Mass index were also improved (Intervention 17.8 vs 18.7 kg/m2; Control 16.3 vs 14.7 kg/m2, p=0.026). Differences in markers of immunity (CD-3 and CD-8) and inflammation (IL-6, VEGF, INF-y, TNFa, MCP-1 and EGF) were observed.ConclusionThe results suggest improved tumour regression and downstaging in the exercise intervention group and should prompt larger studies on this topic.Trial registration numberNCT03626610.
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