| 1. |
- Martinsson, Ulla, et al.
(författare)
-
Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019
- 2023
-
Ingår i: ACTA ONCOLOGICA. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:10, s. 1348-1356
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019.Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position.Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each).Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.
|
|
| 2. |
- Nilsson Hammar, Anna, et al.
(författare)
-
Introduction
- 2022
-
Ingår i: Gender, materiality, and Politics : Essays on the making of power - Essays on the making of power. - 9789189361379 ; , s. 7-21
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 3. |
- Tesi, Bianca, et al.
(författare)
-
Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
-
Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
|
|
| 4. |
- Tesi, Bianca, et al.
(författare)
-
Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
-
Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
|
|
| 5. |
- Hjelmér, Ida, et al.
(författare)
-
Quality of life among female childhood cancer survivors with and without premature ovarian insufficiency
- 2023
-
Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 17:1, s. 101-109
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Due to an increase in survival, a growing population of childhood cancer survivors (CCS) is present. However, female CCS are at risk of developing premature ovarian insufficiency (POI) after cancer treatment. POI involves a decreased chance of conceiving and the increased infertility state has a large impact on affected individuals’ health and mental life. The objective of this study was to investigate health state and well-being among female CCS with and without POI and healthy controls (HC). Methods: Female CCS treated in southern Sweden between 1964 and 2008 were included. Each patient was matched with a HC. The final study population included 167 female CCS and 164 HC that were examined between October 2010 and January 2015 at the Reproductive Medicine Centre at Skåne University Hospital in Malmö, Sweden. All participants, except for two HCs, answered an EQ-5D-3L questionnaire for measuring health state including a visual analogue scale (VAS) for estimating well-being. Results: There were 22 CCS with POI, none of the HC had POI. The mean health state differed among groups (unadjusted: P = 0.002; adjusted: P = 0.007). A difference in mean experienced well-being among groups was noted (unadjusted: P = 0.003; adjusted: P = 0.012). Lowest well-being was found in the CCS group with POI (P = 0.024). Conclusions: Female CCS have a significantly decreased health state and well-being. Female CCS with POI additionally have the lowest self-estimated well-being. Implications for Cancer Survivors: Female CCS with POI should be identified early in order to give them adequate information and support.
|
|
| 6. |
- Kadowaki, Åsa, 1966-, et al.
(författare)
-
Education of the primary health care staff based on acceptance and commitment therapy is associated with reduced sick leave in a prospective controlled trial
- 2021
-
Ingår i: BMC Family Practice. - : BMC. - 1471-2296. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of cognitive behavioral therapy (CBT) to cope with mental distress and pain issues has helped many patients in primary health care in Sweden. However, the effects of CBT to reduce sick leave has not been equally convincing. Acceptance and Commitment Therapy (ACT) is an evolution of traditional CBT and we aimed to study if education based on ACT of the staff rather than the patients could reduce sick leave in primary health care. Methods: This was a prospective trial in 6 primary health care centers in Kalmar (total amount of registered subjects of 28,930) in which the staff (physicians, nurses and therapists) received group-based education according to ACT during 2018 and 2019. The effects were compared with 5 similarly sized control health care centers in the neighboring Region of Jonkoping in which no such education took place. The main aim was to study changes in sick leave in the 6 primary care centers of Kalmar and to keep track of more general trends by studying sick leave also in Jonkoping, letting sick leave in the year 2017 to be the reference period for both areas. Results: The staff at the health care centers in Kalmar reported to having attended a mean of 5.2 +/- 2 educational ACT-sessions with psychiatrist Kadowaki in Kalmar. Sick leave for ICD-10 F43 (reaction to severe stress and related adjustment-disorders) was reduced from a mean value of 28.7 +/- 9.1ongoing sick leaves/month in 2017 to 22.6 +/- 7.0 sick leaves/month in 2018 (-21%, p = 0.033) and to 18.1 +/- 10 sick leaves/month in 2019 (-37%, p = 0.038). The corresponding sick leave for any diagnosis (total sick leave) was reduced from 132 +/- 39 sick leaves/month in 2017 to 118 +/- 38 sick leaves/month in 2018 (-11%, p = 0.056) and to 102 +/- 37 sick leaves/month in 2019 (-21%, p = 0.021). The corresponding sick leave comparisons in the control health centers did not show any significant changes (all p-values >= 0.24). Conclusions: Total monthly mean sick leave was reduced 21% in the health care centers in Kalmar during the second year of the educational ACT intervention of the staff while it was unchanged in Jonkoping. This suggests a significant effect to induce a reduction in long-term sick leave for patients in primary health care in which the staff received education according to ACT. The results of this trial could serve as a basis for a randomized trial in order to ascertain causality.
|
|
| 7. |
- Poulikidou, Sofia, 1984, et al.
(författare)
-
Impacts on fuel producers and customers of conflicting rules for life cycle assessment
- 2022
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The use of life cycle assessment (LCA) as a tool for estimating the environmental performance of a product or service in a holistic and systematic manner is increasing. Fuel producers may need to apply different methodological frameworks to be used in different contexts; internally for product development activities as well as externally for communication with customers or authorities. Different LCA frameworks may vary in scope, system boundaries (i.e. life cycle stages to be considered) or modelling requirements (such as data demands but also more detailed methodological features). They may also vary in terms of information they can provide in relation to the environmental performance of the product. Those variations could lead to conflicting outcomes and conclusions and may also increase complexity for the LCA practitioner leading to high competence and resource requirements. Within the research project: Impacts on fuel producers and customers of conflicting rules for LCA , the requirements of different LCA frameworks and their implications to fuel producers are investigated. Focus has been given on three specific frameworks that are identified as relevant or potentially relevant for fuel producers, namely: the recast of the EU Renewable Energy Directive (referred to here as RED II), the EU framework for Product Environmental Footprint (PEF), and the framework of Environmental Product Declaration (EPD). The aim of the project is to increase understanding on the different LCA frameworks available and identify whether the multitude of such frameworks gives conflicting recommendations for environmental improvements and fuel choices. The three LCA frameworks listed above were applied in case studies. To illustrate the potential differences that the different frameworks may lead to, a variation of production pathways and feedstocks were selected including first generation as well as advanced biofuels. Based on the results obtained it can be concluded that applying all three frameworks is not a straightforward task. The methods contain fundamental differences and are at different levels of development, maturity, and adoption. In certain situations, they can lead to diverging conclusions as a result of different quantitative outcomes for a specific production pathway, thus influencing decision making processes in different directions. Understanding those differences and underlying assumptions is important for understanding the variations in outcome. The result for a specific fuel could differ substantially depending on the framework applied and the assumptions and interpretations made when applying this framework. Certain methodological parameters were identified to have a greater impact on the results than others: • The three frameworks diverge in the methods applied for modelling waste management, which can be very important for the results when the biofuel is produced from waste. • The frameworks diverge in what approaches are allowed for modelling processes with multiple products. This can be very important for the results when the fuel is co-produced with other products. • The frameworks also diverge in how the electricity supply is modelled. This is not very important for the results in most of our case studies, because the production of these biofuels does not require a lot of electricity. The study confirms that applying a framework like EPD or PEF in addition to RED II would require significant supplementary efforts. Not only because of different rules which were often contradicting or difficult to interpret but also because of additional data and reporting requirements. The need for expertise and resources is increasing for fuel producers to be able to provide EPD and PEF compliant assessments. To enhance the development and harmonization of LCA approaches this project stresses the need for product specific rules (in the form of Product Environmental Category Rules (PEFCR) and Product Category Rules (PCR)) for renewable fuels. Future versions of all three studied frameworks should be clearer on how specific methodological choices are to be applied (e.g., when it comes to allocation and multifunctional processes) as well as when it comes to model electricity supply. RED for example shall be clearer on how to define the electricity region while EPD guidelines on how to define the electricity market. Although it is not realistic to aim for a single unified LCA framework, the biofuel PCR and PEFCR can be developed with RED in mind. Some aspects of the PEF methodology can perhaps also be integrated into RED III that is currently under development. This would enhance the broader adoption of the frameworks among fuel producers. Finally, the involvement and engagement of the industry, and fuel producers themselves is very important. Industry initiatives are essential for the development of biofuel PCR and PEFCR while the general development of the three frameworks can also be influenced. In this study, we also investigated the relationship between the LCA frameworks and schemes for chain of custody certification (CoCC), in particular schemes for mass balance certifications (MBC) to investigate to what extent these schemes complement or overlap with LCA. The purpose of MBC schemes and LCA are different, in the sense that the first aim at verifying the sources and sustainability of total amounts of raw materials used by tracking them throughout the value chain, while the second at quantifying specific environmental impact. The system boundaries are similar, since both cover the entire value chain, but may be applied differently depending on the detailed frameworks applied and choices made in applying the MBC schemes. By identifying and clearly illustrating the variations among the studied frameworks the study enhances application, development, and harmonization of LCA, in a broader perspective, informs LCA practitioners but also decision makers and provides insights on how the identified challenges can be addressed.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Andersson, Rebecca, et al.
(författare)
-
Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
- 2021
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- 70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones. We found that Ssa4, when overproduced in cells lacking Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition of aggregates into protein inclusions, and promoted protein degradation. In contrast, Ssa4 overproduction in the Hsp70 deficient cells failed to restore the recruitment of the disaggregase Hsp104 to misfolded/aggregated proteins, to fully restore clearance of protein aggregates, and to bring back the formation of the nucleolus-associated aggregation compartment. Exchanging the nucleotide-binding domain of Ssa4 with that of Ssa1 suppressed this 'defect' of Ssa4. Interestingly, Ssa4 overproduction extended the short lifespan of ssa1 Delta ssa2 Delta mutant cells to a lifespan comparable to, or even longer than, wild type cells, demonstrating that Hsp104-dependent aggregate clearance is not a prerequisite for longevity assurance in yeast. Author summary All organisms have proteins that network together to stabilize and protect the cell throughout its lifetime. One of these types of proteins are the Hsp70s (heat shock protein 70). Hsp70 proteins take part in folding other proteins to their functional form, untangling proteins from aggregates, organize aggregates inside the cell and ensure that damaged proteins are destroyed. In this study, we investigated three closely related Hsp70 proteins in yeast; Ssa1, 2 and 4, in an effort to describe the functional difference of Ssa4 compared to Ssa1 and 2 and to answer the question: What types of cellular stress protection are necessary to reach a normal lifespan? We show that Ssa4 can perform many of the same tasks as Ssa1 and 2, but Ssa4 doesn't interact in the same manner as Ssa1 and 2 with other types of proteins. This leads to a delay in removing protein aggregates created after heat stress. Ssa4 also cannot ensure that misfolded proteins aggregate correctly inside the nucleus of the cell. However, this turns out not to be necessary for yeast cells to achieve a full lifespan, which shows us that as long as cells can prevent aggregates from forming in the first place, they can reach a full lifespan.
|
|
