| 1. |
- 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. |
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| 3. |
- Uden, Theodor, et al.
(författare)
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Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children.
- 2020
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Ingår i: British journal of haematology. - 1365-2141. ; 189:4, s. 745-750
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Tidskriftsartikel (refereegranskat)abstract
- Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non-relapse mortality at four years reached 45% and 22%.
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| 4. |
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| 5. |
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| 6. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 7. |
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| 8. |
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| 9. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 10. |
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| 11. |
- Gericke, Martin, et al.
(författare)
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The European Polysaccharide Network of Excellence (EPNOE) research roadmap 2040: Advanced strategies for exploiting the vast potential of polysaccharides as renewable bioresources
- 2024
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 326
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Tidskriftsartikel (refereegranskat)abstract
- Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.
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| 12. |
- Heinz, Amadeus, et al.
(författare)
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Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification : Data of the European Soft Tissue Sarcoma Registry (SoTiSaR)
- 2023
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 70:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance. Methods: Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018) were retrospectively analyzed. Results: Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p =.17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (+/- 12%) and 31% (+/- 14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (+/- 21%), 20% (+/- 16%), and 13% (+/- 23%, p =.008), respectively. Conclusion: Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups.
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| 13. |
- Heinz, Amadeus T., et al.
(författare)
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Significance of fusion status, Oberlin risk factors, local and maintenance treatment in pediatric and adolescent patients with metastatic rhabdomyosarcoma : Data of the European Soft Tissue Sarcoma Registry SoTiSaR
- 2024
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 71:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Outcome of primary metastatic rhabdomyosarcoma (RMS) is poor. Certain risk factors as fusion status, Oberlin score, and local treatment of primary tumor are known to influence prognosis.Procedure: Patients with metastatic RMS were treated according to Cooperative Weichteilsarkom Studiengruppe (CWS) guidance with chemotherapy (CHT), radiotherapy (RT) excluding total lung irradiation (TLI), complete resection of the primary tumor, and metastasectomy if possible. Kaplan-Meier estimators and Cox proportional hazard models were used to examine event-free survival (EFS) and overall survival (OS) involving also landmark analyses.Results: In the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018), 211 patients were analyzed. Many patients had fusion-positive alveolar RMS (n = 83; 39%). Median age was 9.4 years [0.1-19.7 years]. Treatment primarily consisted of CHT with CEVAIE (carboplatin, epirubicine, vincristine, actinomycin-D, ifosfamide, etoposide: 86%, other regimens: 14%), RT (71%), resection of primary tumor (37%), metastasectomy (19%), and lymph node sampling/dissection (21%). Maintenance treatment (MT) (oral trofosfamide, idarubicin, etoposide) was added in 74% of patients. Oberlin factors, fusion status, and MT were predictive for EFS and OS. MT with O-TIE was not improving outcome when adjusting for the immortal time bias. Local treatment of the primary tumor and radical irradiation (except TLI) improved EFS, not OS, when adjusting for the Oberlin score. Patients with fusion-negative alveolar RMS (n = 9) had an excellent outcome with a 5-year EFS and OS of 100%, compared to patients with embryonal RMS (49%/62%), PAX7- (22%/47%) and PAX3/FOXO1-positive ARMS (10/13%), respectively (p < .001).Conclusions: Prognosis of metastatic RMS primarily depends on fusion status and Oberlin score. Fusion status needs to be considered in future trials to optimize treatment outcome. The role of radical irradiation needs further investigation.
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| 14. |
- Ineland, Jens, et al.
(författare)
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Discursive tensions in late modern society : on education and work for people with intellectual disabilities
- 2015
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Ingår i: European Journal of Social Education. - 1810-4789. ; 26/27, s. 118-136
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Tidskriftsartikel (refereegranskat)abstract
- The article problematizes the way late modern society has contributed to discursive tensions in the welfare state services for people with intellectual disabilities in Sweden. We illustrate how disability practices, such as educational systems and work-life arrangements for people with intellectual disabilities, are characterized by an institutional ambiguity following the institutional logic of the welfare state. By relating to a broader societal perspective, it is argued that the choices of lifestyle among young people with intellectual disabilities are closely linked to the notion of late modern society and its demands for flexibility and constant re-creation of identities. This paradox highlights a challenge for special programme schools as well as disability care organizations, since the dual identity of belonging to both the client category and to an identity constructed through belonging to the civil society characterizes the young generation of persons with intellectual disabilities.
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| 15. |
- Ineland, Jens, et al.
(författare)
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Discursive tensions in late modern society : on education and work for people with intellectual disabilities in Sweden
- 2015
-
Ingår i: European Journal of Social Education. - 1810-4789. ; :26-27, s. 118-136
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Tidskriftsartikel (refereegranskat)abstract
- The article problematizes the way late modern society has contributed to discursive tensions in the welfare state services for people with intellectual disabilities in Sweden. We illustrate how disability practices, such as educational systems and work-life arrangements for people with intellectual disabilities, are characterized by an institutional ambiguity following the institutional logic of the welfare state. By relating to a broader societal perspective, it is argued that the choices of lifestyle among young people with intellectual disabilities are closely linked to the notion of late modern society and its demands for flexibility and constant re-creation of identities. This paradox highlights a challenge for special programme schools as well as disability care organizations, since the dual identity of belonging to both the client category and to an identity constructed through belonging to the civil society characterizes the young generation of persons with ID.
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| 16. |
- Ineland, Jens, 1972-, et al.
(författare)
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Handling Plurality and Dealing with Difficult Work Experiences : A Comparative Study of Human Service Professionals’ Work with Individuals with Intellectual Disabilities
- 2018
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Ingår i: Journal of Policy and Practice in Intellectual Disabilities. - : Wiley. - 1741-1122 .- 1741-1130. ; 15:1, s. 36-42
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Tidskriftsartikel (refereegranskat)abstract
- This article examines how administrators in social services (n = 70) and habilitation staff in healthcare (n = 40) in Sweden experience difficulties in their work with people with intellectual disabilities. The research aim was to investigate the most typical aspects of difficult working situations and to apply a comparative analysis of differences and similarities, where the respondents' organizational affiliations are taken into account. The results are primarily based on a content analysis. Contextual standardized questions were included in this study. The results revealed that experiences of difficulties were categorized in four typological themes: difficult situations associated with (1) structure, (2) professional role, (3) relationships, and (4) collaboration. The respondents' experiences of difficult situations in social services and healthcare organizations did not correspond to the respondents' work dissatisfaction or unclear goals. On the contrary, handling this plurality within a specific organizational context was a fundamental aspect of professionalism. The different characteristics of the organizations in this study reflected two different institutional logics. While the administrators mainly operated within an administrative logic based on a regulatory framework, the habilitation staff operated within a therapeutic logic based on a cognitive framework. Consequently, the two groups had their own specific norms and rule systems, which influenced when, and to what extent, everyday situations were experienced and defined as difficult. The organizational context seems to influence experiences of difficult situations in the work with people with ID and this calls for a discussion of how it impacts the quality of services within intellectual disability services.
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| 17. |
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| 18. |
- Ineland, Jens, 1972-, et al.
(författare)
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Normalitet och identitet i det senmoderna : om personer med intellektuella funktionshinder i relation till utbildning och arbete
- 2013
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Ingår i: Socialvetenskaplig tidskrift. - : Förbundet för forskning i socialt arbete (FORSA). - 1104-1420 .- 2003-5624. ; :1, s. 53-70
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Tidskriftsartikel (refereegranskat)abstract
- Artikeln diskuterar och problematiserar de erfarenheter som unga vuxna personer med intellektuella funktionshinder ger uttryck för i relation till en organisatorisk och samhällelig kontext. En utgångspunkt i artikeln är spänningsförhållandet mellan funktionshinderpolitikens institutionella logik och de idéer, identiteter och föreställningar om framtiden som kommer till uttryck hos unga vuxna personer med intellektuella funktionshinder. Vi relaterar till ett bredare samhällsperspektiv och argumenterar för att nya livsstilsanspråk är nära förknippade med föreställningen om det senmoderna samhället och dess ökade krav på flexibilitet och ständigt återskapande av identiteter.
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| 19. |
- Ineland, Jens, 1972-, et al.
(författare)
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Sources of job satisfaction in intellectual disability services : a comparative analysis of experiences among human service professionals in schools, social services, and public health care in Sweden
- 2018
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Ingår i: Journal of Intellectual & Developmental Disability. - : Informa UK Limited. - 1366-8250 .- 1469-9532. ; 43:4, s. 421-430
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Tidskriftsartikel (refereegranskat)abstract
- Background The research aim of this study was to analyse aspects of job satisfaction in daily work with people with intellectual disability (ID) in schools, social services and health care. Method With a comparative approach we collected data via a digital questionnaire with in total 333 respondents. The empirical material was analysed through a thematic content analysis. Results The result showed that perceptions of job satisfaction could be differentiated into five typological categories: (1) the target group; (2) social rewards; (3) social relations; (4) professional core mission; and (5) results and outcomes. The findings also showed apparent differences in responses, both in terms of frequency and content, which seem to be associated with the respondents' organisational affiliations. Conclusion This study suggests that differences in experiences seem to be associated with work assignments, professional identities and organisational affiliation
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| 20. |
- Ineland, Jens, 1972-, et al.
(författare)
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Utvecklingsstörning, samhälle och välfärd
- 2013. - 2
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- 1. Framväxten av en politik kring funktionshinder --2. Välfärdsarbetets organisatoriska villkor --3. Teoretiska perspektiv på utvecklingsstörning --4. Skola och utbildning --5. Arbetsliv och sysselsättning --6. Familjeliv och föräldraskap --7. Boende och fritid --8. Internet och sociala medier --9. Utvecklingsstörning och hälsa --10. Bemötandets etik i arbete med personer med utvecklingsstörning --11. Framtida utmaningar
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| 21. |
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| 22. |
- Ju, Young Seok, et al.
(författare)
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Somatic mutations reveal asymmetric cellular dynamics in the early human embryo
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 543:7647, s. 714-718
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Tidskriftsartikel (refereegranskat)abstract
- Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.
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| 23. |
- Kaiser, Vera B, et al.
(författare)
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Homozygous loss-of-function variants in European cosmopolitan and isolate populations
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:19, s. 5464-5475
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Tidskriftsartikel (refereegranskat)abstract
- Homozygous Loss of Function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown - as are the phenotypic effects of losing function for most human genes. Here, we make use of 1,432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation.
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| 24. |
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| 25. |
- Meijer, Lisethe, et al.
(författare)
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Serum concentrations of neutral and phenolic organohalogens in pregnant women and some of their infants in The Netherlands.
- 2008
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Ingår i: Environ Sci Technol. - 0013-936X. ; 42:9, s. 3428-33
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Tidskriftsartikel (refereegranskat)abstract
- As part of a large European Union (EU)-funded comparative toxicology and human epidemiology study, EU-Compare, a selection of organohalogen compounds (OHCs) was analyzed in maternal serum, collected at the 35th week of pregnancy, and in cord serum of a number of their infants to determine maternal concentrations and to investigate the extent of transplacental transfer of these compounds. Eight neutral OHCs were analyzed: one polychlorinated biphenyl (PCB: CB-153),4,4'-DDE, five polybrominated diphenyl ethers (PBDEs: BDE-47, BDE-99, BDE-100, BDE-153, and BDE-154), and hexabromocyclododecane (HBCDD). Five phenolic OHCs were analyzed: three hydroxylated PCBs (40H-CB-107, 40H-CB-146, and 40H-CB-187), one hydroxylated PBDE (60H-BDE-47), and pentachlorophenol (PCP). All OHCs, except 60H-BDE-47, were present in maternal and cord serum. The historically identified OHCs showed the highest concentration: 4,4'-DDE (median value 89 ng/g lipid in maternal serum and 68 ng/g lipid in cord serum) and PCP (median value 970 pg/g serum in maternal serum and 1500 pg/g serum in cord serum). HBCDD and the PBDEs were present at much lower concentrations. We conclude that OHCs are present in the serum of pregnant women, and all compounds tested are transferred over the placenta. Because transfer is occurring at a critical stage of infant development, investigation of the health impact is urgent.
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| 26. |
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| 27. |
- Molin, Martin, 1967-, et al.
(författare)
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Handle with Care : Staff Experiences of Difficulties working with People with Intellectual Disabilities
- 2016
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Konferensbidrag (refereegranskat)abstract
- Providing care and support to people with intellectual disabilities (ID) is in several aspects a complex and challenging assignment. It could be argued that this complexity has fundamentally to do with different organizational conditions. Analysing the specfiic characteristics of experienced difficulties could generate a new understanding of the organizational prerequisites of working within intellectual disability services. This presentation examines how LSS administrators (n=70) and habilitation staff (n=40) in Sweden experience difficulties working with people with ID. Drawing upon both quantitative and qualitative data generated from a larger web survey a content analysis was used. In order to complement the qualitative analyses we also used descriptive numerical analyses. The results reveals that staff experiences of difficulties in work with people with ID could be differentiated in four typological themes; (1) Structure, (2) Profession, (3) Relations and (4) Collaboration. As shown in our presentation, experience of difficult situations in human service organizations does not necessarily correspond with work dissatisfaction or unclear goals. On the contrary, we argue that it is a fundamental aspect of professionalism to handle this plurality within a specific organizational context. The different characteristics of the organizations in our study reflect two different institutional logics. While the LSS administrators mainly operates within an administrative logic based on a regulative framework, the habilitation staff are operating within a therapeutic logic based on a cognitive framework. Consequently they have their own specific norms and rule systems, which influence when and to which extent everyday situations are experience and defined as difficult.
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| 28. |
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| 29. |
- Montoliu-Gaya, Laia, et al.
(författare)
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Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.
- 2024
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Ingår i: Acta neuropathologica. - 1432-0533. ; 147:1
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Tidskriftsartikel (refereegranskat)abstract
- Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD=69, non-AD=54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC=89.8), p-tau231 (AUC=83.4), and p-tau205 (AUC=81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR<1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217=15.29, ORp-tau205=5.05 and ORp-tau231=3.86) and Braak staging (ORp-tau217=14.29, ORp-tau205=5.27 and ORp-tau231=4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease.
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| 30. |
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| 31. |
- Salonen, Tapio, et al.
(författare)
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Vi tillsätter en skuggutredning om socionomutbildningen
- 2024
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Annan publikation (populärvet., debatt m.m.)abstract
- Dagens utmaningar behöver mötas genom att vi stärker professionen, skriver debattörer från bland annat Akademikerförbundet SSR, Vision och Föreningen Sveriges Socialchefer.
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| 32. |
- Sauer, Lennart, et al.
(författare)
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Sources of job satisfaction among professionals in intellectual disability services
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This presentation explores sources of job satisfaction among human service professionals working with people with intellectual disabilities. We also explore in what way the organizational context influence these experiences. The data is generated from a larger web survey. A questionnaire was distributed to 640 participants of which 421 answered a standardized question, which yield a response rate on 67 % and 335 respondents answered an open-ended question (52 %), which generated a total of 547 written excerpts. Drawing upon both quantitative and qualitative data a content analysis was used. In order to complement the qualitative analyses descriptive numerical analyses was used. Even though the data shows that the respondents experience heavy work load and psychological strains the vast majority report high ratings on work satisfaction. We argue that it is a fundamental aspect of professionalism to handle this plurality within a specic organizational context. The content analysis revealed that sources of job satisfaction irrespective of organization, is categorized in five different core categories; target group, social rewards, social relations, professional core mission and results/outcomes. We also present and analyze organizational differences in relations to how the response rates are distributed between the five categories.
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| 33. |
- Scheer, Monika, et al.
(författare)
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Synovial sarcoma disease characteristics and primary tumor sites differ between patient age groups : a report of the Cooperative Weichteilsarkom Studiengruppe (CWS)
- 2020
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : SPRINGER. - 0171-5216 .- 1432-1335. ; 146:4, s. 953-960
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Tidskriftsartikel (refereegranskat)abstract
- Background: Older age is associated with worse outcome in synovial sarcoma (SS) patients. Differences in disease presentation among distinct age groups, however, are currently unknown.Methods: SS patients < 21 years registered in consecutive CWS trials over the period of 1981-2018 were evaluated. Characteristics were analyzed according to age groups using the Fisher's exact test.Results: The study population included 432 SS patients. Disease characteristics differed according to age groups of children (0-12 years, n = 176), adolescents (13-16 years, n = 178), and young adults (17-21 years, n = 78). The proportion of invasive tumors (T2) was significantly higher in older patients: children 33%, adolescents 39% and young adults 54%, p = 0.009805. Similarly, the proportion of tumors > 10 cm was higher (13%, 21%, 31%; p = 0.005657) whereas conversely, the proportion of small tumors < 3 cm was lower in older patients (29%, 24%, 6%; p = 0.000104). The presence of metastases at first diagnosis was also highest in older patients (6%, 10%, 21%, p = 0.000963). Notably, the proportion of thigh tumors was higher in older patients (p = 0.04173), whereas the proportion of head-neck tumors was lower in older patients (p = 0.08896).Conclusions The rates of large, invasive tumors and the presence of metastases are significantly associated with older patient age. Localization to the thigh is more frequent in older patients.Discussion The causes for these variations require further exploration.
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| 34. |
- Shlien, Adam, et al.
(författare)
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Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 16:7, s. 2032-2046
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Tidskriftsartikel (refereegranskat)abstract
- Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER)-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.
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| 35. |
- Sparber-Sauer, Monika, et al.
(författare)
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Radiotherapy and long-term sequelae in pediatric patients with parameningeal rhabdomyosarcoma : Results of two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry
- 2024
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 71:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundParameningeal location of rhabdomyosarcoma (PM RMS) is known to be an unfavorable prognostic factor. Scarce data are available on radiotherapy (RT) concepts with regard to outcome.MethodsTreatment and outcome of 395 children with PM RMS registered within two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1995-2021) were evaluated.ResultsPatients were IRS group II (n = 15) and III (n = 380) and received systemic treatment according to the enrolled protocols: I2VA (n = 172), VAIA/CEVAIE (n = 223). Delayed resection was performed in 88/395 (22%) patients, and RT was additionally given in 79/88 (90%) resected patients. RT was the predominant local treatment in 355/395 (90%) patients: hyperfractionated accelerated photon (HART; n = 77), conventionally fractionated photon (n = 91) or proton beam (n = 126), brachytherapy (n = 4), heavy ions (n = 1), not available (n = 56). In the subgroup of RT as only local treatment (n = 278), no intracranial tumor extension and complete remission at end of treatment were significant positive prognostic factors. No significant difference on tumor outcome was seen between different radiotherapy concepts. Long-term toxicity with mostly endocrinological and visual deficiencies was reported in 161/279 (58%) surviving patients with a lower trend after proton beam RT (48%) when compared to HART or conventionally fractionated photon RT (71% and 72%, respectively). Ten-year event-free and overall survival in the overall group were 62% (+/- 5, 95% confidence interval [CI]) and 67% (+/- 5, 95% CI); in the RT-only group 67% (+/- 6, 95% CI) and 71% (+/- 6, 95% CI), respectively.ConclusionCWS data confirm the recent RT concept in PM RMS. Long-term sequelae as endocrinological and visual deficiencies need to be addressed.
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| 36. |
- Tramsen, Lars, et al.
(författare)
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Pediatric Patients with Stage IV Rhabdomyosarcoma Significantly Benefit from Long-Term Maintenance Therapy : Results of the CWS-IV 2002 and the CWS DOK IV 2004-Trials
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma (STS) in childhood. Whereas more than 90% of patients with localized low-risk RMS can be cured, metastatic RMS have a dismal outcome, with survival rates of less than 30%. The HD CWS-96 trial showed an improved outcome for patients receiving maintenance therapy after completing intensive chemotherapy. Consequently, the international clinical trials CWS-IV 2002 and CWS DOK IV 2004 on metastatic disease of STS of the Cooperative Weichteilsarkom Studiengruppe (CWS) were designed in addition to the CWS-2002P trial for localized RMS disease. All patients received a multimodal intensive treatment regimen. To maintain remission, three options were compared: long-term maintenance therapy (LTMT) versus allogeneic hematopoietic stem cell transplantation (alloHSCT) versus high-dose chemotherapy (HDCT). A total of 176 pediatric patients with a histologically confirmed diagnosis of metastatic RMS or RMS-like tumor were included. A total of 89 patients receiving LTML showed a significantly better outcome, with an event-free survival (EFS) of 41% and an overall survival (OS) of 53%, than alloHSCT (n = 21, EFS 19%, p = 0.02, OS 24%, p = 0.002). The outcome of LTML was slightly improved compared to HDCT (n = 13, EFS 35%, OS 34%). In conclusion, our data suggest that in patients suffering from metastatic RMS, long-term maintenance therapy is a superior strategy in terms of EFS and OS compared to alloHSCT. EFS and OS of HDCT are similar in these strategies; however, the therapeutic burden of LTMT is much lower.
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| 37. |
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