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1.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
2.	Hau, Sofie Olsson, et al. (författare) Chemotherapy, host response and molecular dynamics in periampullary cancer : The CHAMP study 2020 Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1 Tidskriftsartikel (refereegranskat)abstract Background: Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the "Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)" study aims to monitor these processes to gain new insight into this perplexing disease. Methods: The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. Discussion: Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. Trial registration: This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.
3.	Wahlin, Sara, et al. (författare) Clinical impact of T cells, B cells and the PD-1/PD-L1 pathway in muscle invasive bladder cancer : a comparative study of transurethral resection and cystectomy specimens 2019 Ingår i: OncoImmunology. - 2162-4011. ; 8:11 Tidskriftsartikel (refereegranskat)abstract In patients with muscle invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) prior to radical cystectomy has improved survival but there is an urgent unmet need to identify prognostic and predictive biomarkers to stratify patients who will benefit from treatment. This study aimed to examine the composition of tumor-infiltrating immune cells in MIBC, with particular reference to the clinical outcome and the potential modifying effect of NAC. To this end, the expression of CD8+ and FoxP3+ T cells, CD20+ B cells, PD-1+ and PD-L1+ immune cells and PD-L1+ tumor cells was evaluated by immunohistochemistry on tissue microarrays with paired transurethral resection (TURB) specimens, cystectomy specimens and lymph node metastases from 145 patients, 65 of whom had received NAC. Kaplan–Meier and Cox regression analyses were applied to assess the impact of investigated cell subsets on time to recurrence (TTR). In cystectomy specimens, high infiltration of the investigated immune cell populations, but not PD-L1+ tumor cells, were independently associated with a prolonged TTR, whereas in TURB specimens, this association was only seen for CD8+ lymphocytes. An additive beneficial prognostic effect of NAC was seen for the majority of the cell subsets but there was no significant interaction between any immune marker and NAC in relation to TTR. Furthermore, no differences in cell densities prior to NAC treatment were observed between complete and non-complete responders, or pre- and posttreatment in non-complete responders. In conclusion, immune cell infiltration provides important prognostic information in both pre- and postsurgical samples of MIBC, independently of NAC.
4.	Albin, Maria, et al. (författare) 0253 Hairdressers are occupationally exposed to ortho- and meta- toluidine 2014 Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 71 Suppl 1, s. 32-33 Konferensbidrag (refereegranskat)abstract Hairdressing work is classified as carcinogenic based on excess risk for bladder cancer. We aimed at evaluating if current hairdressers are exposed to established/suspected bladder carcinogens (aromatic amines) and indicate possible sources of exposure.
5.	Alvehus, Malin, et al. (författare) Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training 2014 Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 114:7, s. 1463-1471 Tidskriftsartikel (refereegranskat)abstract The effects of resistance training on mitochondrial biogenesis and oxidative capacity in skeletal muscle are not fully characterized, and even less is known about alterations in adipose tissue. We aimed to investigate adaptations in oxidative metabolism in skeletal muscle and adipose tissue after 8 weeks of heavy resistance training in apparently healthy young men. Expression of genes linked to oxidative metabolism in the skeletal muscle and adipose tissue was assessed before and after the training program. Body composition, peak oxygen uptake (VO2 peak), fat oxidation, activity of mitochondrial enzyme in muscle, and serum adiponectin levels were also determined before and after resistance training. In muscle, the expression of the genes AdipoR1 and COX4 increased after resistance training (9 and 13 %, respectively), whereas the expression levels of the genes PGC-1 alpha, SIRT1, TFAM, CPT1b, and FNDC5 did not change. In adipose tissue, the expression of the genes SIRT1 and CPT1b decreased after training (20 and 23 %, respectively). There was an increase in lean mass (from 59.7 +/- A 6.1 to 61.9 +/- A 6.2 kg), VO2 peak (from 49.7 +/- A 5.5 to 56.3 +/- A 5.0 ml/kg/min), and fat oxidation (from 6.8 +/- A 2.1 to 9.1 +/- A 2.7 mg/kg fat-free mass/min) after training, whereas serum adiponectin levels decreased significantly and enzyme activity of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase did not change. Despite significant increases in VO2 peak, fat oxidation, and lean mass following resistance training, the total effect on gene expression and enzyme activity linked to oxidative metabolism was moderate.
6.	Andersson, Gustav, et al. (författare) Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival : validatory study of two independent patient cohorts 2014 Ingår i: BMC Urology. - : BioMed Central (BMC). - 1471-2490. ; 14:1, s. 36- Tidskriftsartikel (refereegranskat)abstract Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.
7.	Andersson, Nina, et al. (författare) Lymphocyte antigen 6 superfamily member D is a marker of urothelial and squamous differentiation : Implications for risk stratification of bladder cancer 2020 Ingår i: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Background: Screening across a multitude of normal and malignant tissues revealed an enhanced expression of lymphocyte antigen 6 superfamily member D (LY6D) in squamous epithelium and urothelium, as well as in malignancies derived therefrom. The aim of this study was to further delineate the protein expression of LY6D in urothelial bladder cancer, with particular attention to its relationship with clinicopathological characteristics and patient outcome. Methods: Immunohistochemical expression of LY6D was assessed in tissue microarrays with urothelial bladder cancer tumours from three independent patient cohorts; one with transurethral resection of the bladder (TURB) specimens of mixed tumour stages from 110 consecutive cases, one with tumours of mixed stages from 260 incident cases in a population-based cohort, and one with paired TURB specimens, resected tumours and a subset of lymph node metastases from 145 patients with muscle-invasive bladder cancer (MIBC). Chi-square and non-parametric tests were applied to examine associations of LY6D expression with clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were applied to examine 5-year overall survival (OS) and recurrence free survival (RFS) in relation to LY6D expression. Results: In the two cohorts with mixed stages, positive LY6D expression was denoted in 63 and 64% of the cases, respectively, and found to be significantly higher in low-grade and less invasive tumours. Negative LY6D expression was significantly associated with a reduced 5-year OS, although not independently of established prognostic factors. In the population-based cohort, LY6D expression was higher in tumours with squamous differentiation and lower in other variant histologies compared to pure urothelial tumours, and the association of LY6D expression with survival was somewhat enhanced after exclusion of the former. LY6D expression was generally lower in the MIBC cohort, and even more reduced in resected tumours compared to TURB specimens in patients who had not received neoadjuvant chemotherapy. There were no significant associations between LY6D expression and RFS, neither allover nor in relation to neoadjuvant chemotherapy. Conclusion: LY6D is a marker of urothelial and squamous differentiation that may add useful diagnostic and prognostic information to better guide the clinical management of bladder cancer, given that the presence of variant histology is taken into account.
8.	Andersson, Patrik, 1974, et al. (författare) Framtidsbilder för samhällsbyggnad 2006 Rapport (övrigt vetenskapligt/konstnärligt)abstract Framtidsbilder för samhällsbyggnad 2020De kommande 15 åren står institutionen för Bygg- och miljöteknik inför stora förändringar. Därför har institutionen initierat projektet Framtidsbilder 2020 där man engagerat en framtidspanel bestående av elva yngre disputerade forskare. Arbetet inleddes med ett breddgruppsmöte där 110 personer representerande institutionens personal och studenter deltog. Vid mötet identifierades ett antal trender och osäkra utvecklingar som påverkar framtiden inom samhällsbyggnadsområdet. Deltagarna bidrog också med idéer till en önskvärd utveckling, vilket har sammanställts och utgör grunden till en gemensam önskvärd framtid/vision för institutionen. Materialet från breddgruppsmötet har bearbetats av Framtidspanelen och resulterat i fyra scenarier som beskriver hur samhällsbyggnadsområdet kan se ut år 2020. Syftet med framtidsbilderna är att de ska vara vägledande för institutionens beslut och förhållningssätt under de kommande åren.Fyra scenarierTurning TorsoSamhället präglas av en ekonomi som är på uppgång, och av ett nytänkande och öppet samhälle. Materiell status och individualism är viktigt. Detta leder till en hög arbetsbelastning samt krav på exklusiva varor av hög kvali-tet. Det finns en stor medvetenhet om miljöpåverkan och klimatförändringar och lösningarna för att klara energiförsörjningen är innovativa.Eco-metropolenDet sveper en grön våg genom dagens samhälle. Under de senaste 15 åren har vi insett att jorden skall vara en bebolig plats även åt dem som kommer efter oss. Vi söker ständigt efter nya, mer förfinade metoder att tillvarata de resurser vi har. Samhället och individen är i balans. Ekonomin är god och vi är miljömedvetna, trygga och integrerade. Nytänkande premieras och icke- materialistiska värderingar står högt i kurs. Vi tänker individuellt, men agerar mer än gärna för kollektivets bästa. Utbildning är gratis TrädgårdsstadenEtt samhälle där vi lärt oss hantera stress, men känner oss otrygga och helst umgås i slutna sociala sammanhang. Vi bor enkelt inne i stan, eller gärna på landsbygden nära storstäderna. Minskade behov av högutbildade i samhället gör att vi har svårt att rekrytera studenter till teknikutbildningar. Det traditionella tankesättet leder till kulturkrockar med företag och personer från andra länder.Gated communitiesFörsämrad ekonomi och ökad egoism har lett fram till ett stressat, otryggt och segregerat samhälle. Accelererande klimatförändringar och ökad miljö-påverkan skrämmer oss, men trots det åtgärdar vi inte problemen, utan koncentrerar oss på konsekvenserna. Arbetslöshet i samhällsbyggnadssek-torn leder till sänkt status för samhällsbyggaren. Vi har därför svårt att rekrytera studenter, och även forskningen har låg status.
9.	Arne, Mats, 1954-, et al. (författare) How often is diagnosis of COPD confirmed with spirometry? 2010 Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 104:4, s. 550-556 Tidskriftsartikel (refereegranskat)abstract Background: Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide. Diagnosis is customarily confirmed with spirometry, but there are few studies on documented spirometry use in everyday clinical practice. Methods: In a cross-sectional survey and study of the medical records of primary and secondary care COPD patients aged 18-75 in a Swedish region, patients with COPD were randomly selected from the registers of 56 primary care centres and 14 hospital outpatient clinics. Spirometry data at diagnosis ±6 months were analyzed. Results: From 1,114 patients with COPD, 533 with a new diagnosis of COPD during the four-year study period were identified. In 59% (n=316), spirometry data in connection with diagnosis were found in the medical records. Spirometry data with post-bronchodilator forced expiratory volume in one second (FEV1)/ vital capacity (VC) ratios were available in 45% (n=241). FEV1/VC ratio <0.70 were found in 160 patients, which corresponds to 30% of the patients with a new diagnosis. Lower age, female gender, current smoking, higher body mass index (BMI) and shorter forced exhalation time were related to COPD diagnosis despite an FEV1/VC ratio of ≥0.70. The most common problem in the quality assessment was an insufficient exhalation time. Conclusions: Only a third of Swedish patients with COPD had their diagnosis confirmed with spirometry. Our data indicate that female gender, current smoking, higher BMI and short exhalation time increase the risk of being diagnosed with COPD without fulfilling the spirometric criteria for the disease.
10.	Bernhardsson, Susanne, 1958, et al. (författare) Implementation of physical activity on prescription for children with obesity in paediatric health care (IMPA): protocol for a feasibility and evaluation study using quantitative and qualitative methods 2022 Ingår i: Pilot and Feasibility Studies. - : Springer Science and Business Media LLC. - 2055-5784. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Background: Physical inactivity is a main cause of childhood obesity which tracks into adulthood obesity, making it important to address early in life. Physical activity on prescription (PAP) is an evidence-based intervention that has shown good effect on physical activity levels in adults, but has not been evaluated in children with obesity. This project aims to evaluate the prerequisites, determinants, and feasibility of implementing PAP adapted to children with obesity and to explore children's, parents', and healthcare providers' experiences of PAP. Methods: In the first phase of the project, healthcare providers and managers from 26 paediatric clinics in Region Vastra Gotaland, Sweden, will be invited to participate in a web-based survey and a subset of this sample for a focus group study. Findings from these two data collections will form the basis for adaptation of PAP to the target group and context. In a second phase, this adapted PAP intervention will be evaluated in a clinical study in a sample of approximately 60 children with obesity (ISO-BMI > 30) between 6 and 12 years of age and one of their parents/legal guardians. Implementation process and clinical outcomes will be assessed pre- and post-intervention and at 8 and 12 months' follow-up. Implementation outcomes are the four core constructs of the Normalization Process Theory; coherence, cognitive participation, collective action, and reflexive monitoring; and appropriateness, acceptability, and feasibility of the PAP intervention. Additional implementation process outcomes are recruitment and attrition rates, intervention fidelity, dose, and adherence. Clinical outcomes are physical activity pattern, BMI, metabolic risk factors, health-related quality of life, sleep, and self-efficacy and motivation for physical activity. Lastly, we will explore the perspectives of children and parents in semi-structured interviews. Design and analysis of the included studies are guided by the Normalization Process Theory. Discussion: This project will provide new knowledge regarding the feasibility of PAP for children with obesity and about whether and how an evidence-based intervention can be fitted and adapted to new contexts and populations. The results may inform a larger scale trial and future implementation and may enhance the role of PAP in the management of obesity in paediatric health care in Sweden.
11.	Boman, Charlotte, et al. (författare) Physical activity on prescription for children with obesity: a focus group study exploring experiences in paediatric healthcare 2024 Ingår i: Frontiers in Health Services. - 2813-0146. ; 4 Tidskriftsartikel (refereegranskat)abstract Background: Insufficient physical activity is a growing public health concern and is closely linked to obesity in both adults and children. Swedish physical activity on prescription (PAP) is effective in increasing physical activity levels in adults, but knowledge about how PAP is used in paediatric healthcare is lacking. Therefore, this study aimed to explore experiences of working with PAP for children with obesity amongst paediatric staff and managers. Methods: Seven focus group discussions with 26 participants from paediatric outpatient clinics in western Sweden were conducted. Data were analysed both inductively and deductively, framed by the Normalization Process Theory's four core constructs: coherence, cognitive participation, collective action, and reflexive monitoring. Results: The PAP work for children with obesity was experienced to be about helping children to become physically active, and less about losing weight. Identified barriers for using PAP were the non-uniform nature of the work and a perceived lack of guidelines. Collaboration with physiotherapists and physical activity organisers outside the organisation was identified as an important facilitator. An important contextual factor for implementing PAP is the collaboration between paediatric clinics and physical activity organisers. In the transition between these stakeholders, maintaining a family-centred approach when working with PAP was experienced as challenging. Conclusions: PAP is a well-known intervention that is inconsistently used for children with obesity. The intervention should include a family-centred approach for this patient group. It also needs to align better with existing collaborations with other healthcare units as well as with new forms of collaboration with physical activity organisers in the community.
12.	Boman, Charlotte, et al. (författare) Prerequisites for implementing physical activity on prescription for children with obesity in paediatric health care: a cross-sectional survey 2022 Ingår i: Norsk implementeringskonferens, Oslo, Norge. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
13.	Boman, Charlotte, et al. (författare) Prerequisites for implementing physical activity on prescription for children with obesity in paediatric health care: A cross-sectional survey. 2023 Ingår i: Frontiers in Health Services. - : Frontiers Media SA. - 2813-0146. ; 2 Tidskriftsartikel (refereegranskat)abstract Physical inactivity is a main driver of childhood obesity that tracks into adulthood, making it crucial to address early in life. Swedish physical activity on prescription (PAP) is an effective intervention for increasing physical activity levels in adults and is being implemented in primary care in Sweden. Before implementing PAP for children, both intervention effectiveness and implementation prerequisites need to be examined. Framed by the Normalization Process Theory (NPT) domains, this study aimed to investigate perceptions of PAP amongst paediatric staff and managers working with children with obesity, as well as acceptability, appropriateness, feasibility, and barriers and facilitators for implementing PAP in paediatric health care.Staff and managers in 28 paediatric outpatient clinics in western Sweden were surveyed using validated implementation instruments and open-ended questions. Data were analysed using Mann-Whitney U tests and Kruskal-Wallis tests. Qualitative data were categorised into NPT domains.The survey response rate was 54% (125/229). Most respondents (82%) reported PAP to be familiar and many (56%) perceived it as a normal part of work; nurses and physiotherapists to a greater extent (p<0.001). This was anticipated to increase in the future (82%), especially amongst those with the longest work experience (p=0.012). Respondents reported seeing the potential value in their work with PAP (77%), being open to working in new ways to use PAP (94%), and having confidence in their colleagues' ability to use PAP (77%). Barriers and facilitators were found in all the NPT domains, mainly collective action and reflexive monitoring, where, for example, inadequacies of education, resources, and research on PAP for children were reported as barriers. Most respondents agreed that PAP was acceptable, appropriate, and feasible (71% to 88%).PAP is familiar and perceived as an acceptable, appropriate, and feasible intervention, and by many viewed as a normal part of clinical routines in paediatric outpatient clinics in western Sweden, especially by physiotherapists and nurses. Barriers and faciliators are mainly related to collective action and reflexive monitoring. The wide acceptance demonstrates receptiveness to PAP as an intervention to promote an active lifestyle for children with obesity.
14.	Boman, Erika, 1975- (författare) Inner strength as a health resource among older women 2016 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Background Long life does not inevitably mean more healthy years; older women have an increased risk of disabilities, diseases and adverse life events. Nevertheless, many older women experience health. This may be explained by possessing resources that promote health, despite adversities. Inner strength is seen as a resource as such. In this thesis inner strength is interpreted according to a theoretical model where inner strength comprises four interrelated and interacting dimensions: connectedness, creativity, flexibility and firmness, and being rated by the Inner Strength Scale (ISS).Aim and methods The overall purpose of this thesis was to explore inner strength as a health resource among older women. In study I six focus group interviews were performed with older women (66-84 years; n = 29) and the interviews were analysed by a concept driven approach and by means of qualitative content analysis. Studies II–IV had a quantitative, cross-sectional design. A questionnaire was sent to all older women (65 years and older) living in Åland, an autonomous island community in the Baltic Sea, and 1555 (57%) women responded. The data was analysed using descriptive and inferential statistics.Results In study I, exploring how inner strength and its dimensions can be identified in narratives of older women, connectedness was interpreted as a striving to be in communion, creativity as the ability to make the best of the situation, firmness as having a spirit of determination – “it is all up to you”, and flexibility as a balancing act. The results of study II showed that strong inner strength was associated with better mental health, but not physical health. In exploring factors associated with health-related quality of life, fewer symptoms of depressive disorders was the strongest explanatory variable, and together with not feeling lonely associated with better both physical health and mental health. Better physical health was also explained by not having a diagnosed disease, being of lower age and the opportunity to engage in meaningful leisure activities. Better mental health was additionally explained by having enough money for personal needs. In study III the result showed that non-depressed women were likely to have a strong inner strength, as well as never or seldom feeling lonely, taking fewer prescribed drugs, feeling needed and having the opportunity to engage in meaningful leisure activities. In study IV poorer mental health was associated with weaker inner strength in total, and in all four dimensions of inner strength. Symptoms of depressive disorders and feeling lonely were related to lower scores in three of the dimensions (except firmness and creativity, respectively) and poorer physical health was associated with lower scores in two of the dimensions (firmness and flexibility). Some other health threats were significantly associated with only one of the dimensions (connectedness or creativity), and others were not significantly associated at all.Conclusion The results add nuance to the notion of inner strength and deepen empirical knowledge about the phenomenon. It is elucidated that the ISS can be used not only to rate inner strength but also to offer guidance as to the areas (i.e. dimensions) in which interventions may be profitable. It is further shown that inner strengths can be identified in narratives of older women. Mental ill health has shown to have overall the strongest association with weakened inner strength among community-dwelling older women. The causality can, though, not be studied due to the cross-sectional design; therefore, longitudinal studies are recommended. Notwithstanding that limitation, the findings can be used as a knowledge base in further research within this field.
15.	Boman, Jesper, et al. (författare) Evolution of hybrid inviability associated with chromosome fusions Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Chromosomal rearrangements, such as inversions, have received considerable attention in the speciation literature due to their hampering effects on recombination. However, less is known about how other rearrangements, such as chromosome fissions and fusions, can affect the evolution of reproductive isolation. Here, we used crosses between populations of the wood white butterfly (Leptidea sinapis) with different karyotypes to identify genomic regions associated with hybrid inviability. We mapped candidate loci for hybrid inviability by contrasting allele frequencies between F2 hybrids that survived until the adult stage with individuals of the same cohort that succumbed to hybrid incompatibilities. Hybrid inviability factors were predominantly found in fast-evolving regions with reduced recombination rates, especially in regions where chromosome fusions have occurred. By analyzing sequencing coverage, we excluded aneuploidies as a direct link between hybrid inviability and chromosome fusions. Instead, our results point to an indirect relationship between hybrid inviability and chromosome fusions, possibly related to reductions in recombination rate caused by fusions. These results highlight that the extensive variation in chromosome numbers observed across the tree of life does not only distinguish species but can also be involved in speciation by being hotspots for the early evolution of postzygotic reproductive isolation.
16.	Boman, Karolina, et al. (författare) Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer 2013 Ingår i: BMC Urology. - : Springer Science and Business Media LLC. - 1471-2490. ; 13:April,8, s. 17-17 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Low nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to be associated with poor prognosis in several cancer forms e.g. breast, ovarian, colorectal, prostate cancer and malignant melanoma. The aim of this study was to examine the prognostic impact of RBM3 expression in urinary bladder cancer.METHODS: Immunohistochemical RBM3 expression was examined in tumours from 343 patients with urothelial bladder cancer. Chi-square and Spearman's correlation tests were applied to explore associations between RBM3 expression and clinicopathological characteristics. The impact of RBM3 expression on disease-specific survival (DSS), 5-year overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analysis and Cox proportional hazards modelling.RESULTS: Reduced nuclear RBM3 expression was significantly associated with more advanced tumour (T) stage (p <0.001) and high grade tumours (p=0.004). Negative RBM3 expression was associated with a significantly shorter DSS (HR=2.55; 95% CI 1.68-3.86)) and 5-year OS (HR=2.10; 95% CI 1.56-2.82), also in multivariable analysis (HR=1.65; 95% CI 1.07-2.53 for DSS and HR=1.54; 95% CI 1.13-2.10 for 5-year OS). In patients with Ta and T1 tumours expressing reduced RBM3 levels, Kaplan-Meier analysis revealed a significantly shorter PFS (p=0.048) and 5-year OS (p=0.006).CONCLUSION: Loss of RBM3 expression is associated with clinically more aggressive tumours and an independent factor of poor prognosis in patients with urothelial bladder cancer and a potentially useful biomarker for treatment stratification and surveillance of disease progression.
17.	Boman, Karin, 1946- (författare) Endometrial carcinoma : steroid hormones and receptors in relation to proliferation 1993 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The significance of the hormonal milieu for endometrial changes is as well-known as its link with endometrial carcinoma. Unopposed oestradiol treatment is shown to increase the incidence for this cancer. Obesity leads to elevated levels of oestrogens and is a risk factor for endometrial carcinoma. An association between high tumour proliferation and prognosis is a general feature of human cancer. Tumour growth can be expressed as proliferation rate and flow cytometry (FCM) is a sensitive and reproducable method to estimate S-phase fraction (SPF) and ploidy level. Both parameters have been shown to correlate with prognosis. Sex steroid hormone levels were analysed together with clinical parameters, SPF, and receptors in established endometrial carcinoma.The study consisted of postmenopausal women with endometrial adenocarcinoma. H ormones were analysed in 127 patients, 99 were analysed for FCM and 60 for oestrogen and progesterone receptors. RIA technique was used for hormone assay of oestrone, oestradiol, progesterone, androstenedione and testosterone plasma levels. The receptors were analysed with an immunohistochemical method, and SPF and ploidy level by flow cytometry.A wide range of oestrogen concentrations was found. Some patients had levels comparable to fertile women. Strong correlations were found between body mass index, weight and depth of uterine cavity. No relations were found between receptors and SPF, apart from oestrogen- receptor positive tumours having a lower SPF when compared with receptor negative tumours. The influence of oestradiol on tumour proliferation expressed as SPF was ambiguous. SPF was increased with higher oestradiol levels in the group of peri-diploid, well-differentiated tumours, while a negative correlation was found for the peri-diploid, moderately differentiated tumours. The aneuploid and poorly differentiated tumours had a high SPF regardless of oestradiol concentration. The association between progesterone concentration and SPF was of a more general nature. Progesterone above a threshold level was related to a lower SPF in well-differentiated and moderately differentiated tumours. Thus endogenous progesterone seems to play a role in controlling the tumour’s proliferation activity, in contrast to oestradiol, that had a role which did not appear to relate to proliferation activity in any specific direction. The only stimulative association was seen in well-differentiated tumours, but SPF was still below the mean value for all diploid tumours.
18.	Boman, Karolina, et al. (författare) Membranous expression of podocalyxin-like protein is an independent factor of poor prognosis in urothelial bladder cancer 2013 Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 108:11, s. 2321-2328 Tidskriftsartikel (refereegranskat)abstract Background: Membranous expression of the anti-adhesive glycoprotein podocalyxin-like (PODXL) has previously been found to correlate with poor prognosis in several major cancer forms. Here we examined the prognostic impact of PODXL expression in urothelial bladder cancer. Methods: Immunohistochemical PODXL expression was examined in tissue microarrays with tumours from two independent cohorts of patients with urothelial bladder cancer: n = 100 (Cohort I) and n = 343 (Cohort II). The impact of PODXL expression on disease-specific survival (DSS; Cohort II), 5-year overall survival (OS; both cohorts) and 2-year progression-free survival (PFS; Cohort II) was assessed. Results: Membranous PODXL expression was significantly associated with more advanced tumour (T) stage and high-grade tumours in both cohorts, and a significantly reduced 5-year OS (unadjusted HR = 2.25 in Cohort I and 3.10 in Cohort II, adjusted HR = 2.05 in Cohort I and 2.18 in Cohort II) and DSS (unadjusted HR = 4.36, adjusted HR = 2.70). In patients with Ta and T1 tumours, membranous PODXL expression was an independent predictor of a reduced 2-year PFS (unadjusted HR = 6.19, adjusted HR = 4.60) and DSS (unadjusted HR = 8.34, adjusted HR = 7.16). Conclusion: Membranous PODXL expression is an independent risk factor for progressive disease and death in patients with urothelial bladder cancer.
19.	Boman, Karolina, et al. (författare) Podocalyxin-like and rna-binding motif protein 3 are prognostic biomarkers in urothelial bladder cancer : A validatory study 2017 Ingår i: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 5:1, s. 1-10 Tidskriftsartikel (refereegranskat)abstract Background: Urothelial bladder cancer (UBC) is a disease that often is discovered when the tumour is non-muscle invasive, i.e. in Ta or T1 stage. Some patients will progress into muscle-invasive disease, a potentially deadly condition. Although there are some prognostic models, the need for prognostic and predictive biomarkers is considerate and urgent. Membranous expression of podocalyxin-like protein 1 (PODXL) and low expression of the RNA-binding motif 3 (RBM3) has previously been shown to be associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer, including UBC. In this study, we sought to validate the prognostic impact of PODXL and RBM3 in an independent cohort of UBC. Methods: Using tissue microarrays and immunohistochemistry, PODXL and RBM3 expression was evaluated in 272 incident UBC cases from the prospective, population-based cohort study Malmö Diet and Cancer. Kaplan-Meier analysis and Cox proportional hazards modelling were used to evaluate the prognostic impact of these markers on 5-year overall survival (OS). Results: In line with previous studies, both membranous PODXL expression and low RBM3 expression was significantly associated with disadvantageous clinicopathological features. Membranous PODXL expression was significantly associated with a reduced 5-year overall survival in the entire cohort (univariable HR 3.28; 95% CI 1.89-5.69), but this association did not remain significant in multivariable analysis. In T1 tumours, PODXL was significantly associated with reduced survival in univariable analysis (HR = 2.83; 95% CI 1.04-7.72) and borderline significant in multivariable analysis (HR = 2.60; 95% CI 0.91-7.39). Low RBM3 expression was an independent predictor of a reduced survival in the entire cohort (univariable HR 3.19; 95% CI 2.02-5.04, and multivariable HR 1.85; 95% CI 1.11-3.09), and in T1 tumours (univariable HR 2.64; 95% CI 1.11-6.27, and multivariable HR 2.63; 95% CI 1.01-6.84). Conclusions: A link between membranous PODXL expression and clinically more aggressive tumours was further confirmed, but PODXL expression was not an independent prognostic biomarker in this study. Low RBM3 expression was validated as an independent factor of poor prognosis in UBC, including T1 disease. These findings suggest that these biomarkers could be useful in stratifying patients with non-muscle invasive disease for more aggressive first line treatment.
20.	Carlström, P.A., et al. (författare) Adaptations in peak oxygen consumption and fat oxidation following hypertrophy-induced heavy resistance training 2012 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
21.	Dahmoun, Marju, et al. (författare) Apoptosis, proliferation and sex hormone receptors in untreated endometrial adenocarcinoma : results depending on methods of analysis 2003 Ingår i: Int J Oncol. ; 22, s. 115-122 Tidskriftsartikel (refereegranskat)
22.	Dahmoun, Marju, 1954- (författare) Apoptosis, proliferation, and sex steroid receptors in endometrium and endometrial carcinoma 2003 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract This thesis focuses on the involvement of apoptosis and proliferation in the mechanisms of menstruation and hormonal replacement therapy, HRT, as well as in the mechanisms of progesterone therapy in endometrial carcinoma. The aim of the first study was to investigate endometrium for 4 days before and for 2 days during menstruation. In the epithelium, rapid increase in the apoptotic index, decreasing expression of estrogen receptor α (ER) and progesterone receptor (PR), and minimal proliferation were observed prior to menstruation. In the stroma, an increase in the expression of ER and PR and proliferation was seen before the final decrease, and increased apoptosis was seen during menstruation. Thus, apoptosis is involved in the remodeling of the endometrium during menstruation. Postmenopausal endometrium showed unaffected homeostasis, i.e. unchanged ratio between apoptotic index and Ki-67 index during substitution therapy. ER expression was decreased both in the epithelium and stroma, while PR showed some increase in receptor expression. The unchanged homeostasis contributes to endometrial safety during combined continuous HRT. Unchanged apoptosis and increasing proliferation were observed with increasing tumor grade in 29 patients with endometrioid endometrial carcinoma, which may contribute to greater aggression as tumor grade increases. Decreased proliferation was observed after medroxy-progesterone at 20 mg per day particularly in the foci of maximal proliferation in G1 and G2 tumors. The expression of ER was unchanged, while PR was decreased in the foci of maximal expression for PR in G1 and G2 tumors. Since high proliferation and PR expression also coexisted in the same foci, evaluated in G1 and G2 tumors, the effect of progesterone could be facilitated in these tumor groups. High expression of sex steroid receptors was also a predicting factor for good response to progesterone (= decrease in proliferation), while the amount of stroma could not predict that effect.
23.	Dahmoun, Marju, et al. (författare) Apoptosis, proliferation and sex steroid receptors in superficial parts of human endometrium at the end of the secretory phase 1999 Ingår i: J Clin Endocrinol Metab. ; 84, s. 1737-43 Tidskriftsartikel (refereegranskat)
24.	Dahmoun, Marju, et al. (författare) Intratumoral effects of medroxy-progesterone on proliferation, apoptosis, and sex steroid receptors in endometrioid endometrial adenocarcinoma 2004 Ingår i: Gynecol Oncol. - : Elsevier BV. - 0090-8258. ; 92:1, s. 116-126 Tidskriftsartikel (refereegranskat)
25.	du Bois, A, et al. (författare) Paclitaxel-carboplatin-gemcitabine (TCG) as first-line treatment of ovarian cancer: a prospective multicenter phase II study (AGO-OVAR 8) followed by a prospectively randomized phase III GCIG intergroup study (AGO-OVAR 9, GINECO-TCG, NSGO-OC-0102) comparing TCG with standard TC 2005 Ingår i: Int J Gynecol Cancer: Supplement 3. ; 15, s. 224-225 Tidskriftsartikel (refereegranskat)
26.	Fletcher-Sandersjoo, Alexander, et al. (författare) Stockholm score of lesion detection on computed tomography following mild traumatic brain injury (SELECT-TBI) : study protocol for a multicentre, retrospective, observational cohort study 2022 Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:9 Tidskriftsartikel (refereegranskat)abstract Introduction Mild traumatic brain injury (mTBI) is one of the most common reasons for emergency department (ED) visits. A portion of patients with mTBI will develop an intracranial lesion that might require medical or surgical intervention. In these patients, swift diagnosis and management is paramount. Several guidelines have been developed to help direct patients with mTBI for head CT scanning, but they lack specificity, do not consider the interactions between risk factors and do not provide an individualised estimate of intracranial lesion risk. The aim of this study is to create a model that estimates individualised intracranial lesion risks in patients with mTBI who present to the ED. Methods and analysis This will be a retrospective cohort study conducted at ED hospitals in Stockholm, Sweden. Eligible patients are adults (>= 15 years) with mTBI who presented to the ED within 24 hours of injury and performed a CT scan. The primary outcome will be a traumatic lesion on head CT. The secondary outcomes will be any clinically significant lesion, defined as an intracranial finding that led to neurosurgical intervention, hospital admission >= 48 hours due to TBI or death due to TBI. Machine-learning models will be applied to create scores predicting the primary and secondary outcomes. An estimated 20 000 patients will be included. Ethics and dissemination The study has been approved by the Swedish Ethical Review Authority (Dnr: 2020-05728). The research findings will be disseminated through peer-reviewed scientific publications and presentations at international conferences.
27.	Hellström Ängerud, Karin, et al. (författare) Areas for quality improvements in heart failure care : quality of care from the patient's perspective 2017 Ingår i: Scandinavian Journal of Caring Sciences. - Hoboken : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 31:4, s. 830-838 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Heart failure is a serious condition with high mortality and a high symptom burden. Most patients with heart failure will be taken care of in primary care but the knowledge of how the quality of care is perceived by patients with heart failure is limited.OBJECTIVE: The aim was to explore how patients with heart failure report quality of care, in an outpatient setting.METHODS: Seventy-one patients with a confirmed diagnosis of heart failure and who were cared for in an outpatient setting were included in this cross-sectional study. Quality of care was assessed with a short form of the Quality from the Patient's Perspective questionnaire. The items measured four dimensions, and each item consists of both perceived reality of the received care and its subjective importance.RESULTS: Inadequate quality was identified in three out of four dimensions and in items without dimension affiliation. In total, inadequate quality was identified in 19 out of 25 items. Patients reported the highest level of perceived reality in 'my family member was treated well' and the lowest perceived reality in 'effective treatment for loss of appetite'. Effective treatment for shortness of breath was of the highest subjective importance for the patients.CONCLUSION: Important areas for improvement in the quality of care for patients with heart failure in an outpatient setting were identified, such as symptom alleviation, information, participation and access to care.
28.	Hellström Ängerud, Karin, et al. (författare) Areas for quality improvements in heart failure care: quality of care from the family members' perspective 2018 Ingår i: Scandinavian Journal of Caring Sciences. - Hoboken : Wiley. - 0283-9318 .- 1471-6712. ; 32:1, s. 346-353 Tidskriftsartikel (refereegranskat)abstract BackgroundThe complex needs of people with chronic heart failure (HF) place great demands on their family members, and it is important to ask family members about their perspectives on the quality of HF care. ObjectiveTo describe family members' perceptions of quality of HF care in an outpatient setting. MethodsA cross-sectional study using a short form of the Quality from Patients' Perspective (QPP) questionnaire for data collection. The items in the questionnaire measure four dimensions of quality, and each item consists of both the perceived reality of the care and its subjective importance. The study included 57 family members of patients with severe HF in NYHA class III-IV. ResultsFamily members reported areas for quality improvements in three out of four dimensions and in dimensionless items. The lowest level of perceived reality was reported for treatment for confusion and loss of appetite. Treatment for shortness of breath, access to the apparatus and access to equipment necessary for medical care were the items with the highest subjective importance for the family members. ConclusionFamily members identified important areas for quality improvement in the care for patients with HF in an outpatient setting. In particular, symptom alleviation, information to patients, patient participation and access to care were identified as areas for improvements. Thus, measuring quality from the family members' perspective with the QPP might be a useful additional perspective when it comes to the planning and implementation of changes in the organisation of HF care.
29.	Herzog, Thomas J., et al. (författare) Correlation between CA-125 serum level and response by RECIST in a phase III recurrent ovarian cancer study 2011 Ingår i: Gynecologic Oncology. - New York : Elsevier BV. - 0090-8258 .- 1095-6859. ; 122:2, s. 350-355 Tidskriftsartikel (refereegranskat)abstract Objectives: To evaluate in a large phase III recurrent ovarian cancer trial (OVA-301): 1) the concordance between CA-125 level vs. best overall response (OR) and progression-free survival (PFS) determined by radiological assessment 2) the impact of early CA-125 changes over the subsequent radiological response, and 3) the prognostic value of CA-125 response and CA-125 PFS to predict radiological response and PFS. Methods: Assessment of response in the entire randomized population was performed by the Response Evaluation Criteria in Solid Tumors 1.0 (RECIST) and modified Rustin criteria for CA-125 determination. Results: Most CA-125 decreases were observed in RECIST responders (82% of patients treated with the combination and 74% in the PLD alone). CA-125 progression preceded REC1ST progression in 35% of patients with a median lead time of 8.4 weeks. A high concordance rate between CA-125 PFS status at 4 months (PFS4) and CA-125 response as a predictor of PFS4 (87%) and radiological response (79%) was found in the combination, with high positive predictive value for radiological PFS4 (92%) and high negative predictive value for OR (90%). An early CA-125 decrease was predictive for the ultimate response since it was found in a high rate of RECIST responders. Conclusion: Radiological response was preceded by a favorable predictive CA-125 decrease in a high proportion of patients, suggesting that CA-125 evaluation may be an appropriate tool for tumor assessment in patients with ovarian cancer.
30.	Högberg, Thomas, et al. (författare) Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer-Results from two randomised studies. 2010 Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 46:13, s. 2422-2431 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled. METHODS: Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy. RESULTS: In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01). CONCLUSION: Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.
31.	Höök, Lars, et al. (författare) Dualistic dosage compensation and rapid evolution of expression balance in response to W chromosome degeneration in Leptidea butterflies Annan publikation (övrigt vetenskapligt/konstnärligt)abstract The evolution of dimorphic sex chromosomes from initially homologous autosomes is generally explained by sex-specific selection to maintain linkage between a sex determining locus and genes that are beneficial to the same sex. While initially beneficial, the strong linkage and reduced recombination causes differentiation and degeneration of many initially shared genes. Reduced copy numbers can have severe consequences for the balance of gene expression levels between sex-linked genes and the rest of the genome. Consequently, dosage compensation has evolved independently in different lineages to mitigate the detrimental effects of unbalanced expression of sex-linked genes in the heterogametic sex. However, the variation in sex chromosome regulation in different lineages, puts the need to restore expression to ancestral levels into question. In particular, a general difference has been observed between male- (XY) and female-heterogametic (ZW) systems. In contrast to the X chromosome upregulation in heterogametic males in the XY-systems, the Z chromosomes are rarely upregulated in the heterogametic females in organisms with ZW-systems. Instead, the Z chromosomes are often downregulated in the homogametic males to achieve inter-sexual balance. Although progress has been made to understand what causes this discrepancy, comparative approaches are limited by long divergence times and ancient sex chromosome systems. An attractive approach is therefore to study the evolution of gene regulation on recently derived neo-sex chromosomes, formed through fusions between ancestral sex chromosomes and autosomes. Here, we investigated dosage compensation of neo-sex chromosomes in three closely related butterflies in the cryptic wood white clade (Leptidea). Importantly, the species have acquired multiple sex chromosomes, and dosage compensation could therefore have evolved repeatedly in the clade. Our analyses reveal a mixture of gene expression patterns which suggests that distinct modes of dosage compensation have evolved on the different Z chromosomes. In addition, we detect evidence that dosage balancing mechanisms have been rapidly recruited to the youngest neo-Z chromosome, to counteract an ongoing degeneration of neo-W gametologs. The results add to a growing list of examples where diverse dosage compensation mechanisms can evolve within a single species, and suggests that various regulatory mechanisms are not restricted to specific sex chromosome systems.
32.	Joly, Florence, et al. (författare) Decreased hypersensitivity reactions with carboplatin-pegylated liposomal doxorubicin compared to carboplatin-paclitaxel combination : analysis from the GCIG CALYPSO relapsing ovarian cancer trial 2011 Ingår i: Gynecologic Oncology. - New York : Elsevier BV. - 0090-8258 .- 1095-6859. ; 122:2, s. 226-232 Tidskriftsartikel (refereegranskat)abstract Objective: To describe and analyze observed hypersensitivity reactions (HSR) from the randomized, multicenter phase III CALYPSO trial that evaluated the efficacy and safety of the combination of carboplatin and pegylated liposomal doxorubicin (CD) compared with standard carboplatin–paclitaxel (CP) in patients with platinum-sensitive relapsed ovarian cancer (ROC). Methods: HSR documented within case report forms and SAE reports were specifically analyzed. Analyses were based on the population with allergy of any grade and for grade > 2 allergy. Results: Overall 976 patients were recruited to this phase III trial, with toxicity data available for 466 and 502 on the CD and CP arms, respectively. There was a 15.5% HSR rate associated with CD (2.4% grade > 2) versus 33.1% with CP (8.8% grade > 2), p < 0.001. HSRs occurred more often during first cycle in the CD (46%) arm than in the CP arm (16%). Multivariate predictors of allergy were chemotherapy regimen and age; patients randomized to CD and patients ≥ 70 years old on CP had less allergy. Few patients (< 6%) stopped treatment due to allergy. Allergy rates were higher in patients who did not receive prior supportive treatment; however there was no relationship between allergy and the type of carboplatin product received, or response rate. Conclusions: Use of PLD with carboplatin instead of paclitaxel and older age were the only 2 factors predicting a low rate of HSRs in patients with ROC. CD has previously demonstrated superior progression-free survival and therapeutic index than CP. Taken together these data support the use of CD as a safe and effective therapeutic option for platinum-sensitive ROC.
33.	Jönsson, Stina Karin Maria, 1975- (författare) XPS studies of an organic anode and hole-conductor system : PEDOT-PSS 2002 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract This thesis deals with photoelectron spectroscopy of conducting polymer systems. A particular system, poly(3,4-ethylenedioxythiophene) polystyrenesulfonic acid (PEDOT-PSS), has been the main focus of this work. It is an aqueous colloidal dispersion consisting of doped conjugated polymer PEDOT with counter ions provided by the PSS chains. PEDOT PSS films have previously proven to have a grain-like structure in which the grains have a ~30 Å thick insulating PSS outermost layer. The conductivity of thin PEDOT-PSS films has been improved through adding some high-boiling-point solvents to the PEDOT-PSS blend. With the help of atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and electron spectroscopy for chemical analysis based photon energy depth profiling (ESCAPEDEPF) measurements the reason for this increase has been explained. The major reason is a rearrangement of the morphology, in terms of an increase in the PEDOT to-PSS ratio in the surface region (i.e. the insulating PPS layer is decreased for each grain). The interface of PEDOT-PSS with aluminum (for contacting purposes) has also been studied with XPS and ultraviolet photoelectron spectroscopy (UPS). Due to the many components in the PEDOT-PSS film its reactions with aluminum was difficult to deduce. Therefore the aluminum interfaces with model molecules of each of the components of PEDOT-PSS were investigated to discern this. Phenyl capped EDOT-trimer was used as a model oligomer for neutral PEDOT. It has been shown that aluminum preferentially internets and forms covalent bonds with C-S carbons that causes a rearrangement of the charge density within the oligomer and breaks the n-conjugation. In PEDOT-PSS blends the PEDOT part is left intact and aluminum preferentially reacts with the SO-3 H+ and/or so-3 species of the PSS part. In order to deduce this the model systems PSSH, benzenesulfonic acid and sodium benzenesulfonate were studied. Sodium benzenesulfonate was used to model the PSS-Na+ contamination present in the polymer blend. The fact that aluminum does not internet with PEDOT avoids any break in the conjugation in the system, but it can however lead to dedoping of the PEDOT chains, therefore negatively affecting the mobility in the material and the charge transport across the PEDOT PSS/aluminum interface.
34.	Kaaman, Ann-Catrin, et al. (författare) Contact allergy to sodium metabisulfite: an occupational problem. 2010 Ingår i: Contact dermatitis. - : Wiley. - 1600-0536 .- 0105-1873. ; 63:2, s. 110-2 Tidskriftsartikel (refereegranskat)
35.	Karlsson, Marjam, 1975- (författare) Nano-porous Alumina, a Potential Bone Implant Coating 2004 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract This thesis describes a method of growing a highly adherent nano-porous alumina coating on titanium implant materials, a design which might be useful in hard tissue replacement. Alumina layers were formed by anodisation of aluminium, which had been deposited on titanium and titanium alloys by electron beam evaporation. Mechanical testing showed the coatings’ shear and tensile strength to be ~20MPa and ~10MPa respectively. Human osteoblasts were cultured on purchased membranes, produced in the same way with similar characteristics as the coating mentioned above. Cell viability, proliferation and phenotype were assessed by measuring redox reactions, DNA, tritiated thymidine incorporation and alkaline phosphatase production. Results showed normal osteoblastic growth patterns with increasing cell numbers the first two weeks after which cell growth decreased and alkaline phosphatase production increased, indicating that osteoblastic phenotype was retained on the alumina. Flattened cell morphology with filipodia attached to the pores of the material was seen. Implants frequently trigger inflammatory responses due to accumulation and activation of cells such as polymorphonuclear granulocytes (PMN), also called neutrophils. Activation and morphology of human PMN in response to nano-porous alumina with two pore sizes (20 and 200 nm) was investigated by luminol-amplified chemiluminescence, granule enzyme deposition measurement, optical and scanning electron microscopy. Activation was observed on both membrane types, however less pronounced on the 200 nm alumina. For both membranes a decrease in activation was seen after coating with fibrinogen, collagen I and serum (more pronounced for the two latter). On fibrinogen-coated alumina many flattened cells were observed, indicating frustrated phagocytosis. Finally when culturing osteoblasts on non-coated and collagen-coated membranes (after exposure to PMN) many more cells had established on the protein-coated surface after 24 h. The overall results indicate that it might be possible to produce a novel bone implant coating by anodisation of aluminium deposited on titanium and that this material will support osteoblast adhesion and proliferation. Furthermore neutrophil activation can be suppressed when coating the alumina with collagen I, which is beneficial considering the fact that this protein also is essential for bone formation.
36.	Lindemann, Kristina, et al. (författare) Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO) 2014 Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14 Tidskriftsartikel (refereegranskat)abstract Background: We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma. Methods: We performed an open-label one-arm, two-stage, phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients. Results: Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated. Conclusion: Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients.
37.	Lindstam, M, et al. (författare) Area Selective Laser Chemical Vapour Deposition of Diamond 1995 Ingår i: Mat. Res. Soc. Symp. Proc. 397. Konferensbidrag (refereegranskat)
38.	Liu, Kui, et al. (författare) Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway: new roles for an old timer 2006 Ingår i: Dev Biol. - 0012-1606. ; 299:1, s. 1-11 Tidskriftsartikel (refereegranskat)
39.	Liu, Lian, et al. (författare) Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a 2007 Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 134:1, s. 199-209 Tidskriftsartikel (refereegranskat)abstract In recent years, mammalian oocytes have been proposed to have important roles in the orchestration of ovarian follicular development and fertility. To determine whether intra-oocyte Foxo3a, a component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, influences follicular development and female fertility, a transgenic mouse model was generated with constitutively active Foxo3a expressed in oocytes. We found that the female transgenic mice were infertile, which was caused by retarded oocyte growth and follicular development, and anovulation. Further mechanistic studies revealed that the constitutively active Foxo3a in oocytes caused a dramatic reduction in the expression of bone morphogenic protein 15 (Bmp15), connexin 37 and connexin 43, which are important molecules for the establishment of paracrine and gap junction communications in follicles. Foxo3a was also found to facilitate the nuclear localization of p27(kip1) in oocytes, a cyclin-dependent kinase (Cdk) inhibitor that may serve to inhibit oocyte growth. The results from the current study indicate that Foxo3a is an important intra-oocyte signaling molecule that negatively regulates oocyte growth and follicular development. Our study may therefore give some insight into oocyte-borne genetic aberrations that cause defects in follicular development and anovulation in human diseases, such as premature ovarian failure.
40.	Liu, Lian, et al. (författare) Phosphorylation and inactivation of glycogen synthase kinase-3 by soluble kit ligand in mouse oocytes during early follicular development. 2007 Ingår i: Journal of Molecular Endocrinology. - : Bioscientifica. - 0952-5041 .- 1479-6813. ; 38:1-2, s. 137-146 Tidskriftsartikel (refereegranskat)abstract Communication between mammalian oocytes and their surrounding granulosa cells through the Kit-Kit ligand (KL, or stem cell factor, SCF) system has been shown to be crucial for follicular development. Our previous studies (Reddy et al. 2005, Liu et al. 2006) have indicated that the intra-oocyte KL-Kit-PI3 kinase (PI3K)-Akt-Foxo3a cascade may play an important role in follicular activation and early development. In the present study, using in situ hybridization and in vitro culture of growing oocytes from 8-day-old postnatal mice, we have demonstrated that another Akt substrate, glycogen synthase kinase-3 (GSK-3), is expressed in growing oocytes. Also, treatment of cultured mouse oocytes with soluble KL not only leads to increased Akt kinase activity in the oocytes, which can phosphorylate recombinant GSK-3 in vitro, but also leads to phosphorylation of oocyte GSK-3alpha and GSK-3beta, which can result in the inactivation of GSK-3 function in oocytes. In addition, we have shown that the regulation of GSK-3alpha and GSK-3beta in cultured oocytes by soluble KL is accomplished through PI3K, since the PI3K-specific inhibitor LY294002 completely abolished the KL-induced phosphorylation of GSK-3alpha and GSK-3beta. Moreover, blockage of the Kit signaling pathway by a Kit function-blocking antibody, ACK2, resulted in reduced phosphorylation of GSK-3. Taken together, our data suggest that the cascade from granulosa cell-derived KL to Kit-PI3K-Akt-GSK-3 in oocytes may take part in regulation of oocyte growth and early ovarian follicular development.
41.	Lynöe, Niels, et al. (författare) Informed consent and participants' inclination to delegate decision-making to the doctor. 2004 Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 43:8, s. 769- Tidskriftsartikel (refereegranskat)
42.	M Del Campo, J, et al. (författare) Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m(2) 24 h or 1.3 mg/m(2) 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer 2009 Ingår i: ANNALS OF ONCOLOGY. - : Elsevier BV. - 0923-7534. ; 20:11, s. 1794-802 Tidskriftsartikel (refereegranskat)abstract Patients and methods: Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m(2) 24 h (arm A, n = 54) or 1.3 mg/m(2) 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute-Common Toxicity Criteria v. 2.0. Results: ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3-8.6 months; arm A) and 6.8 months (95% CI 4.6-7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B). Conclusions: Both every-3-weeks trabectedin regimes, 1.5 mg/m(2) 24 h and 1.3 mg/m(2) 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.
43.	Näsvall, Karin, et al. (författare) Base composition, codon usage and patterns of gene sequence evolution in butterflies. 2023 Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 15:8 Tidskriftsartikel (refereegranskat)abstract Coding sequence evolution is influenced by both natural selection and neutral evolutionary forces. In many species, the effects of mutation bias, codon usage and GC-biased gene conversion (gBGC) on gene sequence evolution have not been detailed. Quantification of how these forces shape substitution patterns is therefore necessary to understand the strength and direction of natural selection. Here, we used comparative genomics to investigate the association between base composition and codon usage bias on gene sequence evolution in butterflies and moths (Lepidoptera), including an in-depth analysis of underlying patterns and processes in one species, Leptidea sinapis. The data revealed significant G/C to A/T substitution bias at third codon position with some variation in the strength among different butterfly lineages. However, the substitution bias was lower than expected from previously estimated mutation rate ratios, partly due to the influence of gBGC. We found that A/T-ending codons were overrepresented in most species and there was a negative association between the magnitude of codon usage bias and GC-content in third codon positions. In contrast, the tRNA-gene population in L. sinapis showed higher GC-content at third codon positions compared to coding sequences in general and less overrepresentation of A/T-ending codons. There was an inverse relationship between synonymous substitutions and codon usage bias indicating selection on synonymous sites. We conclude that the evolutionary rate in Lepidoptera is affected by a complex interaction between underlying G/C -> A/T mutation bias and partly counteracting fixation biases, predominantly conferred by overall purifying selection, gBGC and selection on codon usage.
44.	Näsvall, Karin, et al. (författare) Nascent evolution of recombination rate as a consequence of chromosomal rearrangements. Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Reshuffling of genetic variation occurs both by independent assortment of chromosomes and by homologous recombination. Such reshuffling can generate novel allele combinations and break linkage between advantageous and deleterious variants which increases both the potential and the efficacy of natural selection. Here we used high-density linkage maps to characterize global and regional recombination rate variation in two populations of the wood white butterfly (Leptidea sinapis) with distinct karyotypes. The recombination data were combined with estimates of genetic diversity and measures of selection to assess associations between chromosomal rearrangements, crossing over, maintenance of genetic diversity and adaptation. Our data show that the recombination rate is influenced by both chromosome size and karyotype, but that the difference in recombination rate between karyotypes is reduced as a consequence of a higher frequency of double crossovers in larger chromosomes. As expected from effects of selection on linked sites, we observed an overall positive association between recombination rate and genetic diversity in both populations. Our results also revealed a significant effect of chromosomal rearrangements on the rate of intergenic diversity change between populations, but limited effects on polymorphisms in coding sequence. We conclude that chromosomal rearrangements can have considerable effects on the recombination landscape and consequently influence both maintenance of genetic diversity and efficiency of selection in natural populations.
45.	Näsvall, Karin, et al. (författare) Nascent evolution of recombination rate differences as a consequence of chromosomal rearrangements 2023 Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 19:8 Tidskriftsartikel (refereegranskat)abstract Reshuffling of genetic variation occurs both by independent assortment of chromosomes and by homologous recombination. Such reshuffling can generate novel allele combinations and break linkage between advantageous and deleterious variants which increases both the potential and the efficacy of natural selection. Here we used high-density linkage maps to characterize global and regional recombination rate variation in two populations of the wood white butterfly (Leptidea sinapis) that differ considerably in their karyotype as a consequence of at least 27 chromosome fissions and fusions. The recombination data were compared to estimates of genetic diversity and measures of selection to assess the relationship between chromosomal rearrangements, crossing over, maintenance of genetic diversity and adaptation. Our data show that the recombination rate is influenced by both chromosome size and number, but that the difference in the number of crossovers between karyotypes is reduced as a consequence of a higher frequency of double crossovers in larger chromosomes. As expected from effects of selection on linked sites, we observed an overall positive association between recombination rate and genetic diversity in both populations. Our results also revealed a significant effect of chromosomal rearrangements on the rate of intergenic diversity change between populations, but limited effects on polymorphisms in coding sequence. We conclude that chromosomal rearrangements can have considerable effects on the recombination landscape and consequently influence both maintenance of genetic diversity and efficiency of selection in natural populations.
46.	Patthey, Annika, et al. (författare) Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma 2021 Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 60:9, s. 1218-1224 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation.MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records.RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44).CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.
47.	Reddy, Pradeep, et al. (författare) Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development 2005 Ingår i: Dev Biol. - : Elsevier BV. - 0012-1606. ; 281:2, s. 160-170 Tidskriftsartikel (refereegranskat)
48.	Reddy, Pradeep, et al. (författare) Formation of E-cadherin-mediated cell-cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells 2005 Ingår i: Mol Endocrinol. - : The Endocrine Society. - 0888-8809. ; 19:10, s. 2564-2578 Tidskriftsartikel (refereegranskat)abstract E-cadherin is a well characterized adhesion molecule that plays a major role in epithelial cell adhesion. Based on findings that expression of E-cadherin is frequently lost in human epithelial cancers, it has been implicated as a tumor suppressor in carcinogenesis of most human epithelial cancers. However, in ovarian cancer development, our data from the current study showed that E-cadherin expression is uniquely elevated in 86.5% of benign, borderline, and malignant ovarian carcinomas irrespective of the degree of differentiation, whereas normal ovarian samples do not express E-cadherin. Thus, we hypothesize that E-cadherin may play a distinct role in the development of ovarian epithelial cancers. Using an E-cadherin-expressing ovarian cancer cell line OVCAR-3, we have demonstrated for the first time that the establishment of E-cadherin mediated cell-cell adhesions leads to the activation of Akt and MAPK. Akt activation is mediated through the activation of phosphatidylinositol 3 kinase, and both Akt and MAPK activation are mediated by an E-cadherin adhesion-induced ligand-independent activation of epidermal growth factor receptor. We have also demonstrated that suppression of E-cadherin function leads to retarded cell proliferation and reduced viability. We therefore suggest that the concurrent formation of E-cadherin adhesion and activation of downstream proliferation signals may enhance the proliferation and survival of ovarian cancer cells. Our data partly explain why E-cadherin is always expressed during ovarian tumor development and progression.
49.	Ruiz, Nuria Rodriguez, et al. (författare) Data-driven support to decision-making in molecular tumour boards for lymphoma : A design science approach 2022 Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12 Tidskriftsartikel (refereegranskat)abstract Background: The increasing amount of molecular data and knowledge about genomic alterations from next-generation sequencing processes together allow for a greater understanding of individual patients, thereby advancing precision medicine. Molecular tumour boards feature multidisciplinary teams of clinical experts who meet to discuss complex individual cancer cases. Preparing the meetings is a manual and time-consuming process. Purpose: To design a clinical decision support system to improve the multimodal data interpretation in molecular tumour board meetings for lymphoma patients at Karolinska University Hospital, Stockholm, Sweden. We investigated user needs and system requirements, explored the employment of artificial intelligence, and evaluated the proposed design with primary stakeholders. Methods: Design science methodology was used to form and evaluate the proposed artefact. Requirements elicitation was done through a scoping review followed by five semi-structured interviews. We used UML Use Case diagrams to model user interaction and UML Activity diagrams to inform the proposed flow of control in the system. Additionally, we modelled the current and future workflow for MTB meetings and its proposed machine learning pipeline. Interactive sessions with end-users validated the initial requirements based on a fictive patient scenario which helped further refine the system. Results: The analysis showed that an interactive secure Web-based information system supporting the preparation of the meeting, multidisciplinary discussions, and clinical decision-making could address the identified requirements. Integrating artificial intelligence via continual learning and multimodal data fusion were identified as crucial elements that could provide accurate diagnosis and treatment recommendations. Impact: Our work is of methodological importance in that using artificial intelligence for molecular tumour boards is novel. We provide a consolidated proof-of-concept system that could support the end-to-end clinical decision-making process and positively and immediately impact patients. Conclusion: Augmenting a digital decision support system for molecular tumour boards with retrospective patient material is promising. This generates realistic and constructive material for human learning, and also digital data for continual learning by data-driven artificial intelligence approaches. The latter makes the future system adaptable to human bias, improving adequacy and decision quality over time and over tasks, while building and maintaining a digital log.
50.	Sandström, Karin, et al. (författare) Fluorides in Deposits 2018 Konferensbidrag (övrigt vetenskapligt/konstnärligt)

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