| 1. |
- Hau, Sofie Olsson, et al.
(författare)
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Chemotherapy, host response and molecular dynamics in periampullary cancer : The CHAMP study
- 2020
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the "Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)" study aims to monitor these processes to gain new insight into this perplexing disease. Methods: The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. Discussion: Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. Trial registration: This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.
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| 2. |
- Andersson, Nina, et al.
(författare)
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Lymphocyte antigen 6 superfamily member D is a marker of urothelial and squamous differentiation : Implications for risk stratification of bladder cancer
- 2020
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Ingår i: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Screening across a multitude of normal and malignant tissues revealed an enhanced expression of lymphocyte antigen 6 superfamily member D (LY6D) in squamous epithelium and urothelium, as well as in malignancies derived therefrom. The aim of this study was to further delineate the protein expression of LY6D in urothelial bladder cancer, with particular attention to its relationship with clinicopathological characteristics and patient outcome. Methods: Immunohistochemical expression of LY6D was assessed in tissue microarrays with urothelial bladder cancer tumours from three independent patient cohorts; one with transurethral resection of the bladder (TURB) specimens of mixed tumour stages from 110 consecutive cases, one with tumours of mixed stages from 260 incident cases in a population-based cohort, and one with paired TURB specimens, resected tumours and a subset of lymph node metastases from 145 patients with muscle-invasive bladder cancer (MIBC). Chi-square and non-parametric tests were applied to examine associations of LY6D expression with clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were applied to examine 5-year overall survival (OS) and recurrence free survival (RFS) in relation to LY6D expression. Results: In the two cohorts with mixed stages, positive LY6D expression was denoted in 63 and 64% of the cases, respectively, and found to be significantly higher in low-grade and less invasive tumours. Negative LY6D expression was significantly associated with a reduced 5-year OS, although not independently of established prognostic factors. In the population-based cohort, LY6D expression was higher in tumours with squamous differentiation and lower in other variant histologies compared to pure urothelial tumours, and the association of LY6D expression with survival was somewhat enhanced after exclusion of the former. LY6D expression was generally lower in the MIBC cohort, and even more reduced in resected tumours compared to TURB specimens in patients who had not received neoadjuvant chemotherapy. There were no significant associations between LY6D expression and RFS, neither allover nor in relation to neoadjuvant chemotherapy. Conclusion: LY6D is a marker of urothelial and squamous differentiation that may add useful diagnostic and prognostic information to better guide the clinical management of bladder cancer, given that the presence of variant histology is taken into account.
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| 3. |
- Bernhardsson, Susanne, 1958, et al.
(författare)
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Implementation of physical activity on prescription for children with obesity in paediatric health care (IMPA): protocol for a feasibility and evaluation study using quantitative and qualitative methods
- 2022
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Ingår i: Pilot and Feasibility Studies. - : Springer Science and Business Media LLC. - 2055-5784. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Physical inactivity is a main cause of childhood obesity which tracks into adulthood obesity, making it important to address early in life. Physical activity on prescription (PAP) is an evidence-based intervention that has shown good effect on physical activity levels in adults, but has not been evaluated in children with obesity. This project aims to evaluate the prerequisites, determinants, and feasibility of implementing PAP adapted to children with obesity and to explore children's, parents', and healthcare providers' experiences of PAP. Methods: In the first phase of the project, healthcare providers and managers from 26 paediatric clinics in Region Vastra Gotaland, Sweden, will be invited to participate in a web-based survey and a subset of this sample for a focus group study. Findings from these two data collections will form the basis for adaptation of PAP to the target group and context. In a second phase, this adapted PAP intervention will be evaluated in a clinical study in a sample of approximately 60 children with obesity (ISO-BMI > 30) between 6 and 12 years of age and one of their parents/legal guardians. Implementation process and clinical outcomes will be assessed pre- and post-intervention and at 8 and 12 months' follow-up. Implementation outcomes are the four core constructs of the Normalization Process Theory; coherence, cognitive participation, collective action, and reflexive monitoring; and appropriateness, acceptability, and feasibility of the PAP intervention. Additional implementation process outcomes are recruitment and attrition rates, intervention fidelity, dose, and adherence. Clinical outcomes are physical activity pattern, BMI, metabolic risk factors, health-related quality of life, sleep, and self-efficacy and motivation for physical activity. Lastly, we will explore the perspectives of children and parents in semi-structured interviews. Design and analysis of the included studies are guided by the Normalization Process Theory. Discussion: This project will provide new knowledge regarding the feasibility of PAP for children with obesity and about whether and how an evidence-based intervention can be fitted and adapted to new contexts and populations. The results may inform a larger scale trial and future implementation and may enhance the role of PAP in the management of obesity in paediatric health care in Sweden.
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| 4. |
- Boman, Charlotte, et al.
(författare)
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Physical activity on prescription for children with obesity: a focus group study exploring experiences in paediatric healthcare
- 2024
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Ingår i: Frontiers in Health Services. - 2813-0146. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insufficient physical activity is a growing public health concern and is closely linked to obesity in both adults and children. Swedish physical activity on prescription (PAP) is effective in increasing physical activity levels in adults, but knowledge about how PAP is used in paediatric healthcare is lacking. Therefore, this study aimed to explore experiences of working with PAP for children with obesity amongst paediatric staff and managers. Methods: Seven focus group discussions with 26 participants from paediatric outpatient clinics in western Sweden were conducted. Data were analysed both inductively and deductively, framed by the Normalization Process Theory's four core constructs: coherence, cognitive participation, collective action, and reflexive monitoring. Results: The PAP work for children with obesity was experienced to be about helping children to become physically active, and less about losing weight. Identified barriers for using PAP were the non-uniform nature of the work and a perceived lack of guidelines. Collaboration with physiotherapists and physical activity organisers outside the organisation was identified as an important facilitator. An important contextual factor for implementing PAP is the collaboration between paediatric clinics and physical activity organisers. In the transition between these stakeholders, maintaining a family-centred approach when working with PAP was experienced as challenging. Conclusions: PAP is a well-known intervention that is inconsistently used for children with obesity. The intervention should include a family-centred approach for this patient group. It also needs to align better with existing collaborations with other healthcare units as well as with new forms of collaboration with physical activity organisers in the community.
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| 5. |
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| 6. |
- Boman, Charlotte, et al.
(författare)
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Prerequisites for implementing physical activity on prescription for children with obesity in paediatric health care: A cross-sectional survey.
- 2023
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Ingår i: Frontiers in Health Services. - : Frontiers Media SA. - 2813-0146. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Physical inactivity is a main driver of childhood obesity that tracks into adulthood, making it crucial to address early in life. Swedish physical activity on prescription (PAP) is an effective intervention for increasing physical activity levels in adults and is being implemented in primary care in Sweden. Before implementing PAP for children, both intervention effectiveness and implementation prerequisites need to be examined. Framed by the Normalization Process Theory (NPT) domains, this study aimed to investigate perceptions of PAP amongst paediatric staff and managers working with children with obesity, as well as acceptability, appropriateness, feasibility, and barriers and facilitators for implementing PAP in paediatric health care.Staff and managers in 28 paediatric outpatient clinics in western Sweden were surveyed using validated implementation instruments and open-ended questions. Data were analysed using Mann-Whitney U tests and Kruskal-Wallis tests. Qualitative data were categorised into NPT domains.The survey response rate was 54% (125/229). Most respondents (82%) reported PAP to be familiar and many (56%) perceived it as a normal part of work; nurses and physiotherapists to a greater extent (p<0.001). This was anticipated to increase in the future (82%), especially amongst those with the longest work experience (p=0.012). Respondents reported seeing the potential value in their work with PAP (77%), being open to working in new ways to use PAP (94%), and having confidence in their colleagues' ability to use PAP (77%). Barriers and facilitators were found in all the NPT domains, mainly collective action and reflexive monitoring, where, for example, inadequacies of education, resources, and research on PAP for children were reported as barriers. Most respondents agreed that PAP was acceptable, appropriate, and feasible (71% to 88%).PAP is familiar and perceived as an acceptable, appropriate, and feasible intervention, and by many viewed as a normal part of clinical routines in paediatric outpatient clinics in western Sweden, especially by physiotherapists and nurses. Barriers and faciliators are mainly related to collective action and reflexive monitoring. The wide acceptance demonstrates receptiveness to PAP as an intervention to promote an active lifestyle for children with obesity.
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| 7. |
- Fletcher-Sandersjoo, Alexander, et al.
(författare)
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Stockholm score of lesion detection on computed tomography following mild traumatic brain injury (SELECT-TBI) : study protocol for a multicentre, retrospective, observational cohort study
- 2022
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Mild traumatic brain injury (mTBI) is one of the most common reasons for emergency department (ED) visits. A portion of patients with mTBI will develop an intracranial lesion that might require medical or surgical intervention. In these patients, swift diagnosis and management is paramount. Several guidelines have been developed to help direct patients with mTBI for head CT scanning, but they lack specificity, do not consider the interactions between risk factors and do not provide an individualised estimate of intracranial lesion risk. The aim of this study is to create a model that estimates individualised intracranial lesion risks in patients with mTBI who present to the ED. Methods and analysis This will be a retrospective cohort study conducted at ED hospitals in Stockholm, Sweden. Eligible patients are adults (>= 15 years) with mTBI who presented to the ED within 24 hours of injury and performed a CT scan. The primary outcome will be a traumatic lesion on head CT. The secondary outcomes will be any clinically significant lesion, defined as an intracranial finding that led to neurosurgical intervention, hospital admission >= 48 hours due to TBI or death due to TBI. Machine-learning models will be applied to create scores predicting the primary and secondary outcomes. An estimated 20 000 patients will be included. Ethics and dissemination The study has been approved by the Swedish Ethical Review Authority (Dnr: 2020-05728). The research findings will be disseminated through peer-reviewed scientific publications and presentations at international conferences.
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| 8. |
- Näsvall, Karin, et al.
(författare)
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Base composition, codon usage and patterns of gene sequence evolution in butterflies.
- 2023
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 15:8
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Tidskriftsartikel (refereegranskat)abstract
- Coding sequence evolution is influenced by both natural selection and neutral evolutionary forces. In many species, the effects of mutation bias, codon usage and GC-biased gene conversion (gBGC) on gene sequence evolution have not been detailed. Quantification of how these forces shape substitution patterns is therefore necessary to understand the strength and direction of natural selection. Here, we used comparative genomics to investigate the association between base composition and codon usage bias on gene sequence evolution in butterflies and moths (Lepidoptera), including an in-depth analysis of underlying patterns and processes in one species, Leptidea sinapis. The data revealed significant G/C to A/T substitution bias at third codon position with some variation in the strength among different butterfly lineages. However, the substitution bias was lower than expected from previously estimated mutation rate ratios, partly due to the influence of gBGC. We found that A/T-ending codons were overrepresented in most species and there was a negative association between the magnitude of codon usage bias and GC-content in third codon positions. In contrast, the tRNA-gene population in L. sinapis showed higher GC-content at third codon positions compared to coding sequences in general and less overrepresentation of A/T-ending codons. There was an inverse relationship between synonymous substitutions and codon usage bias indicating selection on synonymous sites. We conclude that the evolutionary rate in Lepidoptera is affected by a complex interaction between underlying G/C -> A/T mutation bias and partly counteracting fixation biases, predominantly conferred by overall purifying selection, gBGC and selection on codon usage.
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| 9. |
- Näsvall, Karin, et al.
(författare)
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Nascent evolution of recombination rate differences as a consequence of chromosomal rearrangements
- 2023
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 19:8
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Tidskriftsartikel (refereegranskat)abstract
- Reshuffling of genetic variation occurs both by independent assortment of chromosomes and by homologous recombination. Such reshuffling can generate novel allele combinations and break linkage between advantageous and deleterious variants which increases both the potential and the efficacy of natural selection. Here we used high-density linkage maps to characterize global and regional recombination rate variation in two populations of the wood white butterfly (Leptidea sinapis) that differ considerably in their karyotype as a consequence of at least 27 chromosome fissions and fusions. The recombination data were compared to estimates of genetic diversity and measures of selection to assess the relationship between chromosomal rearrangements, crossing over, maintenance of genetic diversity and adaptation. Our data show that the recombination rate is influenced by both chromosome size and number, but that the difference in the number of crossovers between karyotypes is reduced as a consequence of a higher frequency of double crossovers in larger chromosomes. As expected from effects of selection on linked sites, we observed an overall positive association between recombination rate and genetic diversity in both populations. Our results also revealed a significant effect of chromosomal rearrangements on the rate of intergenic diversity change between populations, but limited effects on polymorphisms in coding sequence. We conclude that chromosomal rearrangements can have considerable effects on the recombination landscape and consequently influence both maintenance of genetic diversity and efficiency of selection in natural populations.
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| 10. |
- Patthey, Annika, et al.
(författare)
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Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 60:9, s. 1218-1224
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation.MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records.RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44).CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.
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