Estrogen receptor β signalling in mammary epithelial and breast cancer cells

Estrogens are key players in the etiology and progression of breast cancer, and mediate their effects through the estrogen receptors (ERα and ERβ). ERα plays important roles in proliferation and progression of breast cancer, whereas a distinct function of ERβ in the initiation and development of breast cancer is not yet clearly established. The general aim of this thesis was to increase our understanding of the molecular and cellular mechanisms of estrogen signalling in the normal and cancerous breast, focusing on the potential anti-tumourigenic effect of ERβ. Using cell lines with endogenous expression or inducible expression of ERβ we have characterised possible pathways of how ERβ could mediate its anti-tumourigenic effects. The role of ERβ in cell proliferation and cell cycle regulation has been characterised, mainly in vitro. In paper I we investigated how ERβ re-expression would affect breast cancer cells in in vivo. Presence of ERβ in breast cancer xenografts reduced tumour growth and the number of intratumoural blood vessels. Expression of the pro-angiogenic growth factors vascular endothelial growth factor and platelet-derived growth factor β were also reduced upon ERβ expression, both in vitro and in vivo. These findings suggested an anti-tumourigenic role for ERβ by inhibiting growth and angiogenesis. Studies in ERβ-/- mice have suggested a role for ERβ in the regulation of cell adhesion. In paper II we looked at cell-cell adhesion with a focus on E-cadherin. We reported that decrease of ERβ in mammary epithelial cells was associated with a decrease of E-cadherin protein levels through different posttranscriptional regulatory mechanisms, including protein shedding, internalisation and degradation. This correlated with an increase in β-catenin transcriptional activity and impaired morphogenesis on Engelbreth-Holm-Swarm matrix. This study suggests that ERβ has an important role in maintaining cell adhesion and a differentiated phenotype. In paper III we analysed the effects of ERβ on cell-extracellular matrix adhesion. We found that integrin α1 and integrin β1 levels increased in breast cancer cells following ERβ expression. Also, the formation of vinculin containing focal complexes and actin filaments was enhanced, correlating to a more adhesive potential as seen by adhesion to ECM proteins. Furthermore, the migratory potential of the breast cancer cells was decreased upon ERβ expression. This study indicates that ERβ affects integrin expression and clustering and consequently adhesion and migration of breast cancer cells. ERβ has been implicated as an indicator of endocrine response in breast cancer. In paper IV we investigated if ERβ could modulate pathways implicated in endocrine resistance development. Expression of ERβ in human breast cancer cells resulted in a decrease in both active Akt, as well as its upstream regulator, the epidermal growth factor receptor 2 and 3 (HER2/HER3) dimer. Expression of the tumour suppressor and important inhibitor of Akt signalling, PTEN was increased upon expression of ERβ. Further, ERβ expressing breast cancer cells had also an increased sensitivity to tamoxifen. In all, these data provide a possible mechanistic insight into how ERβ may contribute to endocrine sensitivity. In conclusion, the studies presented in this thesis contribute to the knowledge of ERβ function in normal and cancerous breast, and highlight several possible anti-tumourigenic mechanisms for ERβ. Although the mechanisms have not yet been fully characterised, in breast cancer, ERβ seems to affect growth, adhesion, angiogenesis and sensitivity to endocrine therapy. These studies highlight the importance of ERβ as a prospective prognostic marker with potential as a target in the treatment of breast cancer

Validation of Canopy Height Profile methodology for small-footprint full-waveform airborne LiDAR data in a discontinuous canopy environment

A Canopy Height Profile (CHP) procedure presented in Harding et al. (2001) for large footprint LiDAR data was tested in a closed canopy environment as a way of extracting vertical foliage profiles from LiDAR raw-waveform. In this study, an adaptation of this method to small-footprint data has been shown, tested and validated in an Australian sparse canopy forest at plot- and site-level. Further, the methodology itself has been enhanced by implementing a dataset-adjusted reflectance ratio calculation according to Armston et al. (2013) in the processing chain, and tested against a fixed ratio of 0.5 estimated for the laser wavelength of 1550nm. As a by-product of the methodology, effective leaf area index (LAIe) estimates were derived and compared to hemispherical photography-derived values. To assess the influence of LiDAR aggregation area size on the estimates in a sparse canopy environment, LiDAR CHPs and LAIes were generated by aggregating waveforms to plot- and site-level footprints (plot/site-aggregated) as well as in 5m grids (grid-processed). LiDAR profiles were then compared to leaf biomass field profiles generated based on field tree measurements. The correlation between field and LiDAR profiles was very high, with a mean R2 of 0.75 at plot-level and 0.86 at site-level for 55 plots and the corresponding 11 sites. Gridding had almost no impact on the correlation between LiDAR and field profiles (only marginally improvement), nor did the dataset-adjusted reflectance ratio. However, gridding and the dataset-adjusted reflectance ratio were found to improve the correlation between raw-waveform LiDAR and hemispherical photography LAIe estimates, yielding the highest correlations of 0.61 at plot-level and of 0.83 at site-level. This proved the validity of the approach and superiority of dataset-adjusted reflectance ratio of Armston et al. (2013) over a fixed ratio of 0.5 for LAIe estimation, as well as showed the adequacy of small-footprint LiDAR data for LAIe estimation in discontinuous canopy forests

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

To alleviate pain and suffering - a cultural perspective

Vi lever i ett allt mer multikulturellt samhälle, år 2004 passerade Sveriges befolkning 9 miljoner och vid den tidpunkten var 1, 1 miljoner människor i landet utrikes födda. Detta ökar kravet på vården och inte minst för oss blivande sjuksköterskor. Vi måste öka vår kunskap för att kunna tillgodose dessa människors behov och uppnå den hälso- och sjukvårdslag som säger att alla människor har rätt till en god vård på lika villkor. Syftet med denna studie var att få ökad förståelse kring hur sjuksköterskan kan lindra smärta och lidande för patienter med annan kulturell bakgrund. Som teoretisk referensram i arbetet används Madeleine Leiningers modell ” The Sunrise Model”, vilken syftar till att hjälpa sjuksköterskan att bedriva en kulturellt anpassad omvårdnad. Leininger har formulerat tre strategier som sjuksköterskan har till sin hjälp i det praktiska arbetet. Dessa strategier samt andra teorier om hur sjuksköterskan kan lindra smärta och lidande beskrivs i bakgrunden. Studien är en litteraturstudie där resultatet bygger på tolv vetenskapliga artiklar. Utifrån artiklarna har tre teman identifierats för att försöka besvara syftet; kommunikation, kulturell kunskap och sjuksköterskans förhållningssätt. Ur artiklarna anges att den bristande kommunikationen främst beror på tre anledningar; språkliga hinder, kulturella uttryck och otillräcklig information. Den kulturella kunskapen handlar om synen på mat, familj och anhöriga, religionens betydelse samt hur sjuksköterskan kan lindra smärta och lidande. Sjuksköterskans förhållningssätt tar upp hur sjuksköterskan i sitt sätt att vara kan lindra smärta och lidande. Dessa tre teman har sedan diskuterats tillsammans med Leiningers strategier och andra teorier för öka förståelsen kring hur sjuksköterskan kan lindra smärta och lidande för patienter med annan kulturell bakgrund. Resultatet visade att Leiningers strategier på olika sätt kan användas för att finna konkreta tillvägagångssätt att anpassa vården på. Begreppet vårdlidande berörs också för att ge ytterligare perspektiv på vad en icke kulturellt anpassad vård kan resultera i

Anpassning av säljprocessen vid inträde på en ny marknad : En fallstudie inom Public Safety-industrin

The increasing globalization has lead companies to venture into new areas of business, and thereby new markets. When entering a new market, it is important to gain market knowledge to be able to satisfy the customers’ needs. Companies are no longer competing only with products and services; they are also striving to increase their competitive advantage by improving the processes that ultimately deliver the result. In order to obtain competitive advantages, designing business processes to meet the needs of the customers is therefore vital for companies to succeed. Entries into new markets may therefore require adaption to new customers in order to sustain the purpose of the processes. For a telecommunications company venturing into the market of Public Safety, changing preconditions for customers are inevitable, why companies must be aware of changes in the customer’s needs and requirements. When preconditions are changed in this sense, adaptions to the supplier’s sales process might be necessary in order to enable building a relationship between the supplier and the customer. The aim of this study is therefore to establish how companies active in the telecommunications industry can adapt their sales process to new customer requirements and needs when entering the market of Public Safety. This to address the issues that may arise when the established sales process is no longer suited to new customers’ needs and requirements. The thesis is based on a case study at a global telecommunications company, which recently entered the Public Safety market. To create a greater understanding of subjects and findings presented in the report, a literature review touching on the structure of the sales process as well as the preconditions surrounding public procurement is presented. To further create an understanding of the case company’s sales process, nine in-depth interviews were conducted with employees active in the process. In order to draw conclusions on how the sales process should be adapted to Public Safety, five in-depth interviews with customers were conducted. Through analysis, seven underlying needs of the customers could be identified. Further analysis has focused on whether the case company fulfills these needs and aimed to identify gaps between the sales process and the customers’ procurement process. Based on the analysis, recommendations for companies who are entering markets where the customers have similar needs were formulated. One major conclusion of this thesis is that customers within the Public Safety market value traits in a supplier that are not specified as requirements in the formal tender documents. Furthermore, the conclusions expand on these traits and touches on their impact on the customer’s assessment of the supplier. The conclusions also connect the findings of the study to the theory presented, consequently emphasizing how companies should adapt their sales processes to better meet the customer needs.Validerat; 20160629 (global_studentproject_submitter)</p

Anpassning av säljprocessen vid inträde på en ny marknad : En fallstudie inom Public Safety-industrin

The increasing globalization has lead companies to venture into new areas of business, and thereby new markets. When entering a new market, it is important to gain market knowledge to be able to satisfy the customers’ needs. Companies are no longer competing only with products and services; they are also striving to increase their competitive advantage by improving the processes that ultimately deliver the result. In order to obtain competitive advantages, designing business processes to meet the needs of the customers is therefore vital for companies to succeed. Entries into new markets may therefore require adaption to new customers in order to sustain the purpose of the processes. For a telecommunications company venturing into the market of Public Safety, changing preconditions for customers are inevitable, why companies must be aware of changes in the customer’s needs and requirements. When preconditions are changed in this sense, adaptions to the supplier’s sales process might be necessary in order to enable building a relationship between the supplier and the customer. The aim of this study is therefore to establish how companies active in the telecommunications industry can adapt their sales process to new customer requirements and needs when entering the market of Public Safety. This to address the issues that may arise when the established sales process is no longer suited to new customers’ needs and requirements. The thesis is based on a case study at a global telecommunications company, which recently entered the Public Safety market. To create a greater understanding of subjects and findings presented in the report, a literature review touching on the structure of the sales process as well as the preconditions surrounding public procurement is presented. To further create an understanding of the case company’s sales process, nine in-depth interviews were conducted with employees active in the process. In order to draw conclusions on how the sales process should be adapted to Public Safety, five in-depth interviews with customers were conducted. Through analysis, seven underlying needs of the customers could be identified. Further analysis has focused on whether the case company fulfills these needs and aimed to identify gaps between the sales process and the customers’ procurement process. Based on the analysis, recommendations for companies who are entering markets where the customers have similar needs were formulated. One major conclusion of this thesis is that customers within the Public Safety market value traits in a supplier that are not specified as requirements in the formal tender documents. Furthermore, the conclusions expand on these traits and touches on their impact on the customer’s assessment of the supplier. The conclusions also connect the findings of the study to the theory presented, consequently emphasizing how companies should adapt their sales processes to better meet the customer needs.Validerat; 20160629 (global_studentproject_submitter)</p

Sleep disturbances among Swedish soldiers after military service abroad

Aims Since 1956, more than 100,000 Swedish soldiers have served abroad on various international missions. The aim of this paper was to determine whether there was a connection between military service abroad and sleep disorders among Swedish soldiers. Methods The prevalence of sleep disturbances among 1,080 veterans from Kosovo and Afghanistan was compared with almost 27,000 Swedes from a general population sample, using propensity score matching and logistic regression. The sleep disturbances studied were habitual snoring, difficulty inducing sleep (DIS), difficulty maintaining sleep (DMS), early morning awakenings (EMA), and excessive daytime sleepiness (EDS). Insomnia was defined as having at least one of DIS, DMS, or EMA. The covariates used in the matching and adjustments were age, gender, smoking habits, BMI, education, ever having had asthma, moist snuff, and exercise habits. Results The veterans had a significantly lower prevalence of insomnia (26.2% versus 30.4%) and EDS (22.7% versus 29.4%) compared with a matched group from the reference population, using propensity score matching. Analyses with logistic regression showed that belonging to the military population was related to a lower risk of having DMS (adjusted OR (95% CI) 0.77 (0.64-0.91)), insomnia (OR 0.82 (0.71-0.95)), and EDS (OR 0.74 (0.63-0.86)), whereas no significant difference was found for snoring, DIS, and EMA. Conclusion Swedish veterans have fewer problems with insomnia and daytime sleepiness than the general Swedish population. The explanation of our findings may be the selection processes involved in becoming a soldier and when sampling personnel for military assignments abroad

Introduction: minorities and the making of European welfare

The development of welfare states across Europe in the twentieth century had different outcomes for different segments of society. In this special issue the dual character of welfare – that is, the aim of alleviating distress and creating social cohesion while creating divisions when determining who is deserving of what – is studied through the lens of ethnic and social minorities. Minorities, grouped together through joint experiences, heritage and/or social classifi-cations, have been subjected to both inclusionary and exclusionary welfare policies. Thus, welfare in the form of social services, social security, education and health care is a key component in addres-sing, maintaining and creating majority-minority divisions. This article introduces the contributions to the special issue and outlines their historiographical and conceptual foundations. Special atten-tion is given to how the authors in the special issue define welfare and minorities, as well as how the articles contribute to the study of these fields. In the introduction, we argue for a need to study the implications of welfare for minorities case by case, while at the same time outlining principal ways that minorities and welfare have been interlinked