| 1. |
- Høland, Maren, et al.
(författare)
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Transcriptomic subtyping of malignant peripheral nerve sheath tumours highlights immune signatures, genomic profiles, patient survival and therapeutic targets
- 2023
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Ingår i: EBioMedicine. - 2352-3964. ; 97
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malignant peripheral nerve sheath tumour (MPNST) is an aggressive orphan disease commonly affecting adolescents or young adults. Current knowledge of molecular tumour biology has been insufficient for development of rational treatment strategies. We aimed to discover molecular subtypes of potential clinical relevance. Methods: Fresh frozen samples of MPNSTs (n = 94) and benign neurofibromas (n = 28) from 115 patients in a European multicentre study were analysed by DNA copy number and/or transcriptomic profiling. Unsupervised transcriptomic subtyping was performed and the subtypes characterized for genomic aberrations, clinicopathological associations and patient survival. Findings: MPNSTs were classified into two transcriptomic subtypes defined primarily by immune signatures and proliferative processes. “Immune active” MPNSTs (44%) had sustained immune signals relative to neurofibromas, were more frequently low-grade (P = 0.01) and had favourable prognostic associations in a multivariable model of disease-specific survival with clinicopathological factors (hazard ratio 0.25, P = 0.003). “Immune deficient” MPNSTs were more aggressive and characterized by proliferative signatures, high genomic complexity, aberrant TP53 and PRC2 loss, as well as high relative expression of several potential actionable targets (EGFR, ERBB2, EZH2, KIF11, PLK1, RRM2). Integrated gene-wise analyses suggested a DNA copy number-basis for proliferative transcriptomic signatures in particular, and the tumour copy number burden further stratified the transcriptomic subtypes according to patient prognosis (P < 0.01). Interpretation: Approximately half of MPNSTs belong to an “immune deficient” transcriptomic subtype associated with an aggressive disease course, PRC2 loss and expression of several potential therapeutic targets, providing a rationale for molecularly-guided intervention trials. Funding: Research grants from non-profit organizations, as stated in the Acknowledgements.
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| 2. |
- Andersson, Maria, et al.
(författare)
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Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting
- 2019
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : SPRINGER. - 0934-9723 .- 1435-4373. ; 38:7, s. 1223-1234
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Tidskriftsartikel (refereegranskat)abstract
- Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important. Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock. A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012-2013. The criterion early appropriate antibiotic treatment was defined as administration of the first dose of adequate antibiotics within 1h, and the second dose given with less than 25% delay after the recommended dose interval. A high-risk patient was defined as a septic patient with either shock within 24h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality. Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment. Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor.
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| 3. |
- Beausang, Angela, et al.
(författare)
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"Möjligheten att rädda några av dessa kvinnors liv har inte vägts in"
- 2014
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Ingår i: Dagens Medicin. - : Dagens Medicin.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Namnet på Socialstyrelsens vägledning lyder: Hur upptäcka våldsutsatthet? Ja, det kan man verkligen fråga sig efter att ha läst detta föga vägledande dokument, skriver ett stort antal kritiska debattörer.
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| 4. |
- Bogren, Malin, 1970, et al.
(författare)
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Midwifery education, regulation and association in six South Asian countries--a descriptive report.
- 2012
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Ingår i: Sexual & reproductive healthcare : official journal of the Swedish Association of Midwives. - : Elsevier BV. - 1877-5764. ; 3:2, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- To describe the situation of midwifery education, regulation and association in six South Asian countries: Afghanistan, Bangladesh, Bhutan, India, Nepal, and Pakistan.Data were collected via three questionnaires, constructed by the International Confederation of Midwives (ICM) and United Nations Population Fund (UNFPA) Investing in Midwives Programme, used at a regional workshop in Bangladesh, 2010. Selected for the purpose of this study were 55 out of 134 questions of which two were open-ended. The answers from structured closed-ended questions were analyzed with descriptive statistics and the open ended answers with a qualitative content analysis.There was a variation in midwifery education across South Asia, in terms of entry level, competencies and requirements for teachers. None of the countries had national legislation that recognized midwifery as an autonomous profession. Four of the countries had a midwifery association. Two countries had a curriculum based on ICM's essential competences for basic midwifery practice. Main recommendations for improving formal midwifery education across the countries were development of legislation, strengthened formal midwifery education, strengthened professional value, and an improved learning environment.The findings might benefit the future midwifery profession in South Asia and is an important step in addressing the MDGs to reduce maternal and newborn morbidity and mortality in the region. With assistance, the area of South Asia will be able to create autonomous midwives that comply with ICM's global standards for midwifery education and regulation.
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| 5. |
- Danne, Thomas, et al.
(författare)
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A cross-sectional international survey of continuous subcutaneous insulin infusion in 377 children and adolescents with type 1 diabetes mellitus from 10 countries
- 2005
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Ingår i: Pediatric Diabetes. - 1399-543X .- 1399-5448. ; 6:4, s. 193-198
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To document current practices using continuous subcutaneous insulin infusion (CSII) by downloading electronically the 90-d pump data held within the pump memory and relating that to clinical data from children and adolescents in different pediatric diabetes centers from Europe and Israel. Methods: Data of patients (1-18 yr) treated with CSII in 23 centers from nine European countries and Israel were recorded with the ENCAPTURE software (PEC International, Frankfurt, Germany). The number of patients who participated was 377 (48% female, mean diabetes duration ± SD: 6.8 ± 3.7 yr, age: 12.9 ± 3.8 yr, preschool n = 33, prepubertal n = 95, adolescent n = 249, CSII duration: 1.6 ± 1.2 yr, local HbA1c: 8.1 ± 1.2%). Results: The total insulin dose was lower than previously reported for injection therapy (0.79 ± 0.20 U/kg/d). Covariance coefficient of daily total insulin was high in all age groups (adolescents 19 ± 9%, prepubertal 18 ± 8 and preschool 17 ± 8). The distribution of basal insulin infusion rates over 24 hr (48 ± 12% of total dose) varied significantly between centers and age groups. The number of boluses per day (7 ± 3) was not significantly different between the age groups (average daily bolus amount: 0.42 ± 0.16 U /kg). The rate of severe hypoglycemia (coma/convulsions) was 12.4 episodes per 100 patient-years and the number of diabetes-related hospital days was 124 per 100 patient-years. Discussion: Pediatric CSII patients show a high variability in their insulin therapy. This relates both to age-dependent differences in the distribution of basal insulin as to the age-independent day-to-day variation in prandial insulin. © Blackwell Munksgaard, 2005.
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| 6. |
- de Kluizenaar, Yvonne, et al.
(författare)
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Annoyance and disturbed sleep due to road traffic noise: The importance of the least exposed side - QSIDE
- 2013
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Ingår i: The 42nd International Congress and Exposition on Noise Control Engineering Inter-Noise 2013, 15-18 September, Innsbruck, Austria.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: In urban areas, road traffic noise is a dominant source of environmental noise and a major cause of noise annoyance and disturbed sleep. It has been hypothesized that respondents highly exposed to noise at multiple sides of their dwelling, may be expected to be worse off than respondents with the same exposure at the most exposed side, but also having a quiet side to their dwelling. Previous studies provide support for this hypothesis, however to date only a limited number of studies have investigated this hypothesis. There is a need for strengthening existing evidence, and for further quantification of the effects. Methods: Within the EU project QSIDE, the effect of the least exposed facade on annoyance and sleep response is studied in different EU cities in Sweden, Belgium and the Netherlands, including Gothenburg, Stockholm, Antwerp, Gent and Amsterdam. Results: In this paper we discuss the general picture arising from the outcome of these studies. We discuss what the implications may be for new situations (urban planning) and existing high exposure situations (noise abatement measures). Conclusion: The noise environment may be improved by taking into account the exposure levels, and promoting quietness, at the least exposed façade.
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| 7. |
- Dirks-Mulder, Anita, et al.
(författare)
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Exploring the evolutionary origin of floral organs of Erycina pusilla, an emerging orchid model system
- 2017
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Ingår i: BMC Evolutionary Biology. - : BIOMED CENTRAL LTD. - 1471-2148. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thousands of flowering plant species attract pollinators without offering rewards, but the evolution of this deceit is poorly understood. Rewardless flowers of the orchid Erycina pusilla have an enlarged median sepal and incised median petal ('lip') to attract oil-collecting bees. These bees also forage on similar looking but rewarding Malpighiaceae flowers that have five unequally sized petals and gland-carrying sepals. The lip of E. pusilla has a 'callus' that, together with winged 'stelidia', mimics these glands. Different hypotheses exist about the evolutionary origin of the median sepal, callus and stelidia of orchid flowers. Results: The evolutionary origin of these organs was investigated using a combination of morphological, molecular and phylogenetic techniques to a developmental series of floral buds of E. pusilla. The vascular bundle of the median sepal indicates it is a first whorl organ but its convex epidermal cells reflect convergence of petaloid features. Expression of AGL6 EpMADS4 and APETALA3 EpMADS14 is low in the median sepal, possibly correlating with its petaloid appearance. A vascular bundle indicating second whorl derivation leads to the lip. AGL6 EpMADS5 and APETALA3 EpMADS13 are most highly expressed in lip and callus, consistent with current models for lip identity. Six vascular bundles, indicating a stamen-derived origin, lead to the callus, stelidia and stamen. AGAMOUS is not expressed in the callus, consistent with its sterilization. Out of three copies of AGAMOUS and four copies of SEPALLATA, EpMADS22 and EpMADS6 are most highly expressed in the stamen. Another copy of AGAMOUS, EpMADS20, and the single copy of SEEDSTICK, EpMADS23, are most highly expressed in the stelidia, suggesting EpMADS22 may be required for fertile stamens. Conclusions: The median sepal, callus and stelidia of E. pusilla appear to be derived from a sepal, a stamen that gained petal identity, and stamens, respectively. Duplications, diversifying selection and changes in spatial expression of different MADS-box genes shaped these organs, enabling the rewardless flowers of E. pusilla to mimic an unrelated rewarding flower for pollinator attraction. These genetic changes are not incorporated in current models and urge for a rethinking of the evolution of deceptive flowers.
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| 8. |
- Downey, Harriet, et al.
(författare)
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Training future generations to deliver evidence-based conservation and ecosystem management
- 2021
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Ingår i: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
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Forskningsöversikt (refereegranskat)abstract
- 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
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| 9. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 10. |
- Høland, Maren, et al.
(författare)
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Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53
- 2018
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 31:11, s. 1694-1707
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Tidskriftsartikel (refereegranskat)abstract
- Malignant peripheral nerve sheath tumor is a rare and aggressive disease with poor treatment response, mainly affecting adolescents and young adults. Few molecular biomarkers are used in the management of this cancer type, and although TP53 is one of few recurrently mutated genes in malignant peripheral nerve sheath tumor, the mutation prevalence and the corresponding clinical value of the TP53 network remains unsettled. We present a multi-level molecular study focused on aberrations in the TP53 network in relation to patient outcome in a series of malignant peripheral nerve sheath tumors from 100 patients and 38 neurofibromas, including TP53 sequencing, high-resolution copy number analyses of TP53 and MDM2, and gene expression profiling. Point mutations in TP53 were accompanied by loss of heterozygosity, resulting in complete loss of protein function in 8.2% of the malignant peripheral nerve sheath tumors. Another 5.5% had MDM2 amplification. TP53 mutation and MDM2 amplification were mutually exclusive and patients with either type of aberration in their tumor had a worse prognosis, compared to those without (hazard ratio for 5-year disease-specific survival 3.5, 95% confidence interval 1.78–6.98). Both aberrations had similar consequences on the gene expression level, as analyzed by a TP53-associated gene signature, a property also shared with the copy number aberrations and/or loss of heterozygosity at the TP53 locus, suggesting a common “TP53-mutated phenotype” in as many as 60% of the tumors. This was a poor prognostic phenotype (hazard ratio = 4.1, confidence interval:1.7–9.8), thus revealing a TP53-non-aberrant patient subgroup with a favorable outcome. The frequency of the “TP53-mutated phenotype” warrants explorative studies of stratified treatment strategies in malignant peripheral nerve sheath tumor.
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| 11. |
- Ikander, Peder, et al.
(författare)
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Measurement of breast volume is a useful supplement to select candidates for surgical breast reduction
- 2014
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Ingår i: Danish Medical Journal. - 2245-1919. ; 61:1, s. 4760-4760
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The indication for breast reduction in a public welfare or an insurance paid setting depends on the severity of the subjective symptoms and the clinical evaluation. The purpose of this study was to evaluate the use of breast volume as an objective criterion to establish the indication for breast reduction surgery, thus establishing a standard decision basis that can be shared by surgeons and departments to secure patients fair and equal treatment opportunities. MATERIAL AND METHODS: A total of 427 patients who were referred to three Danish public hospitals with breast hypertrophy in the period from January 2007 to March 2011 were included prospectively in the study. The patient's subjective complaints, height, weight and standard breast measurements were registered as well as the decision for or against surgery. Breast volume was measured using transparent plastic cups. RESULTS: Cut-off values for breast volume were calculated based on whether or not the patients were offered reduction surgery. Most patients (93%) with a breast volume below 800 cc were not offered surgery, while most with a volume exceeding 900 cc were offered surgery (94%). In the grey zone between 800 and 900 cc, the indication seemed to be less clear-cut, and additional parameters need to be included. CONCLUSION: Breast volume can be used as an objective criterion in addition to the presently used criteria. Breast volume can easily be measured and has become appreciated by plastic surgeons dealing with patients with breast hypertrophy as a tool which facilitates their decision-making and patients' acceptance of the decisions made.
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| 12. |
- Radón, Anita, 1980-
(författare)
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The Rise of Luxury Brands Online : A study of how a sense of luxury brand is created in an online environment
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Luxury brands have only recently tapped into the online market in an attempt to increase revenues and expand their businesses. This leap onto the online world has resulted in several new challenges, including the luxury brand paradox. The luxury brand paradox concerns the inherent difficulty for luxury brands to increase sales and expand their customer base while simultaneously maintaining an aura of mystery and exclusivity. The openness and accessibility of the Internet are believed to pose an extra challenging environment for luxury brands. This research explores how a sense of luxury brand is created in an online environment. Using methodology comprised of different online methods to comprehend what is taking place online, this study primarily concentrates on visual imagery and online communication. The online world of luxury brands is conceptualized into three distinct categories: brand websites, counterfeit websites and community websites. Using these three categories, the thesis demonstrates what role they each play in the creation of a sense of luxury brand. From this analysis, four themes emerge on the sense of a luxury brand (luxury history, authenticity, community and paradox). The concept of an online fair is used to illustrate the environment of luxury brands on the Internet. The online fair consists of a confluence of people involved in it as well as the various activities they perform. In addition, the fairground where the people participate and the activities that take place are described. In conclusion, this thesis proposes a move from the identity-image construct toward a view of handling and co-creation of sense of brand.
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| 13. |
- Stangeland, Biljana, et al.
(författare)
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AtMBD8 is involved in control of flowering time in the C24 ecotype of Arabidopsis thaliana
- 2009
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Ingår i: Physiologia Plantarum. - : Blackwell Publishing. - 0031-9317 .- 1399-3054. ; 136:1, s. 110-126
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Tidskriftsartikel (refereegranskat)abstract
- The Arabidopsis thaliana accession C24 is a vernalization-responsive, moderately late flowering ecotype. We report that a mutation in AtMBD8, which encodes a protein with a putative Methyl-CpG-Binding Domain (MBD), in C24 background, results in a delay in flowering time during both long and short days. The atmbd8-1 mutant responded to vernalization as wild type (wt) plants. Consistent with a role in modulation of flowering time, an AtMBD8::GUS-reporter construct was expressed in the shoot meristem region and developing leaves. Full-genome transcriptional profiling revealed very few changes in gene expression between atmbd8-1 and wt plants. The expression level of FLC, the major repressor of transition to flowering, was unchanged in atmbd8-1, and in accordance with that, genes upstream of FLC were unaffected by the mutation. The expression level of CONSTANS, involved in photoperiodic control of flowering, was very similar in atmbd8-1 and wt plants. In contrast, the major promoters of flowering, FT, and SOC1, were both downregulated. As FT is a regulator of SOC1, we conclude that AtMBD8 is a novel promotor of flowering that acts upstream of FT in the C24 accession. In contrast to atmbd8-1, the Colombia (Col) SALK T-DNA insertion line, atmbd8-2, did not display a delayed transition to flowering. Transcriptional profiling revealed that a substantial number of genes were differentially expressed between C24 and Col wt seedlings. Several of these genes are also differentially expressed in late flowering mutants. We suggest that these differences contribute to the contrasting effect of a mutation in AtMBD8 in the two ecotypes.
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| 14. |
- Stangeland, Biljana, et al.
(författare)
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Molecular analysis of Arabidopsis endosperm and embryo promoter trap lines : Reporter-gene expression can result from T-DNA insertions in antisense orientation, in introns and in intergenic regions, in addition to sense insertion at the 5′ end of genes
- 2005
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Ingår i: Journal of Experimental Botany. - : Oxford University Press. - 0022-0957 .- 1460-2431. ; 56:419, s. 2495-2505
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Tidskriftsartikel (refereegranskat)abstract
- Random insertions of promoterless reporter genes in genomes are a common tool for identifying marker lines with tissue-specific expression patterns. Such lines are assumed to reflect the activity of endogenous promoters and should facilitate the cloning of genes expressed in the corresponding tissues. To identify genes active in seed organs, plant DNA flanking T-DNA insertions (T-DNAs) have been cloned in 16 Arabidopsis thaliana GUS-reporter lines. T-DNAs were found in proximal promoter regions, 5' UTR or intron with GUS in the same (sense) orientation as the tagged gene, but contrary to expectations also in inverted orientation in the 5' end of genes or in intergenic regions. RT-PCR, northern analysis, and data on expression patterns of tagged genes, compared with the expression pattern of the reporter lines, suggest that the expression pattern of a reporter gene will reflect the pattern of a tagged gene when inserted in sense orientation in the 5' UTR or intron. When inserted in the promoter region, the reporter-gene expression patterns may be restricted compared with the endogenous gene. Among the trapped genes, the previously described nitrate transporter gene AtNRT1.1, the cyclophilin gene ROC3, and the histone deacetylase gene AtHD2C were found. Reporter-gene expression when positioned in antisense orientation, for example, in the SLEEPY1 gene, is indicative of antisense expression of the tagged gene. For T-DNAs found in intergenic regions, it is suggested that the reporter gene is transcribed from cryptic promoters or promoters of as yet unannotated genes.
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