94 research outputs found

    Orsaker varför folk besöker biografer idag och i framtiden

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    Detta examensarbete handlar om biobranschen i Finland. Syftet med studien Ă€r att undersöka vilka faktorer som pĂ„verkar folk att besöka biografer idag och i framti-den. Bland annat följande frĂ„gor diskuteras och undersöks: Varför besöker folk bio-grafer? Hur ofta kommer man att besöka biografer i framtiden? Varför kunde folk tĂ€nka sig gĂ„ oftare pĂ„ bio i framtiden? I arbetet presenteras biografernas verksamhet samt deras stĂ€llning i Finland. Branschens viktiga historiska skeden presenteras frĂ„n biografernas födsel i Finland fram till Ă„ret 2015. I delen med biografernas historia diskuteras Ă€ven internets inverkan pĂ„ biobranschen. I arbetet diskuteras biografernas förĂ€ndringar pĂ„ kulturell och teknologisk nivĂ„ och deras inverkan pĂ„ branschen. I examensarbetet presenteras och analyseras en biografundersökning. Undersökning-en jĂ€mför olika gruppers konsumentbeteendeskillnader. Undersökningen analyseras och diskuteras med hjĂ€lp av figurer och tabeller med tre olika infallsvinklar per enkĂ€tfrĂ„ga. Dessa infallsvinklar handlar om eventuella skillnader mellan mĂ€n och kvinnor, olika Ă„ldersgrupper samt olika konsumentgrupper gĂ€llande deras biobesök. Även andra inverkande faktorer pĂ„ biobranschen som andra medel för filmtittande behandlas i undersökningen. PĂ„ basis av undersökningen kan man dra bland annat den slutsatsen att det finns signifikanta skillnader mellan olika Ă„ldersgrupper nĂ€r det gĂ€ller biobesök. De yngre Ă„ldersgrupperna i undersökningen anser det vara viktigare att se de nyaste filmerna dĂ„ man jĂ€mför med de Ă€ldre Ă„ldersgrupperna. Detta Ă€r bland annat en av orsakerna till varför de yngre Ă„ldersgrupperna besöker biografer.This thesis is about the cinema industry of Finland. The purpose of the thesis is to investigate why people visit cinemas today and in the future. Among other questions, these questions are discussed and investigated in the thesis: Why do people go to cinemas? How often will cinemas be visited in the future? What are the reasons for people to think they will visit cinemas more often in the future? The current situation of Finnish cinemas and their different acts are presented in the thesis. The most important phases of the Finnish cinema history is presented from the birth of cinemas in Finland all the way till the year 2015. In the history part of the thesis the effects of internet towards the cinema industry is discussed. The technological and cultural changes during the history of the culture of cinemas in Finland is discussed in the the-sis. A cinema research of consumer behavior from different consumer group aspects at cinemas is presented and analyzed. The results of the research is analyzed and demonstrated with different figures and tables of three different consumer group aspects. These aspects are about the possible differences between men and women, different age groups and different consumer groups towards the different questions in the research. Other possible effects on the cinema industry, such as other ways for watching movies, is discussed. According to the research the younger age groups think it is more important to see the latest movies when we compare to the older groups. This is one among other reasons why the younger groups visit cinemas

    Identification of two abundant Aerococcus urinae cell wall-anchored proteins

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    Aerococcus urinae is an emerging pathogen that causes urinary tract infections, bacteremia and infective endocarditis. The mechanisms through which A. urinae cause infection are largely unknown. The aims of this study were to describe the surface proteome of A. urinae and to analyse A. urinae genomes in search for genes encoding surface proteins. Two proteins, denoted Aerococcal surface protein (Asp) 1 and 2, were through the use of mass spectrometry based proteomics found to quantitatively dominate the aerococcal surface. The presence of these proteins on the surface was also shown using ELISA with serum from rabbits immunized with the recombinant Asp. These proteins had a signal sequence in the amino-terminal end and a cell wall-sorting region in the carboxy-terminal end, which contained an LPATG-motif, a hydrophobic domain and a positively charged tail. Twenty-three additional A. urinae genomes were sequenced using Illumina HiSeq technology. Six different variants of asp genes were found (denoted asp1-6). All isolates had either one or two of these asp-genes located in a conserved locus, designated Locus encoding Aerococcal Surface Proteins (LASP). The 25 genomes had in median 13 genes encoding LPXTG-proteins (range 6-24). For other Gram-positive bacteria, cell wall-anchored surface proteins with an LPXTG-motif play a key role for virulence. Thus, it will be of great interest to explore the function of the Asp proteins of A. urinae to establish a better understanding of the molecular mechanisms by which A. urinae cause disease

    Treatment with p33 Curtails Morbidity and Mortality in a Histone-Induced Murine Shock Model.

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    Collateral damage caused by extracellular histones has an immediate impact on morbidity and mortality in many disease models. A significant increase in the levels of extracellular histones is seen in critically ill patients with trauma and sepsis. We showed that histones are released from necrotic cells in patients with invasive skin infections. Under in vitro conditions, endogenous p33, an endothelial surface protein also known as the gC1q receptor, interacts with histones released from damaged endothelial cells. Functional analyses have revealed that recombinantly expressed p33 completely neutralizes the harmful features of histones, i.e. hemolysis of erythrocytes, lysis of endothelial cells and platelet aggregation. We also noted that mice treated with a sublethal dose of histones developed severe signs of hemolysis, thrombocytopenia and lung tissue damage already 10 min after inoculation. These complications were fully counteracted when p33 was administered together with the histones. Moreover, application of p33 significantly improved survival in mice receiving an otherwise lethal dose of histones. Together, our data suggest that treatment with p33 is a promising therapeutic approach in severe infectious diseases. © 2014 S. Karger AG, Basel

    New, Useful Criteria for Assessing the Evidence of Infection in Sepsis Research.

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    OBJECTIVES The Sepsis-3 definition states the clinical criteria for sepsis but lacks clear definitions of the underlying infection. To address the lack of applicable definitions of infection for sepsis research, we propose new criteria, termed the Linder-Mellhammar criteria of infection (LMCI). The aim of this study was to validate these new infection criteria. DESIGN A multicenter cohort study of patients with suspected infection who were admitted to emergency departments or ICUs. Data were collected from medical records and from study investigators. SETTING Four academic hospitals in Sweden, Switzerland, the Netherlands, and Germany. PATIENTS A total of 934 adult patients with suspected infection or suspected sepsis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Agreement of infection site classification was measured using the LMCI with Cohen Îș coefficient, compared with the Calandra and Cohen definitions of infection and diagnosis on hospital discharge as references. In one of the cohorts, comparisons were also made to adjudications by an expert panel. A subset of patients was assessed for interobserver agreement. MEASUREMENTS AND MAIN RESULTS The precision of the LMCI varied according to the applied reference. LMCI performed better than the Calandra and Cohen definitions (Îș = 0.62 [95% CI, 0.59-0.65] vs Îș = 0.43 [95% CI, 0.39-0.47], respectively) and the diagnosis on hospital discharge (Îș = 0.57 [95% CI, 0.53-0.61] vs Îș = 0.43 [95% CI, 0.39-0.47], respectively). The interobserver agreement for the LMCI was evaluated in 91 patients, with agreement in 77%, Îș = 0.72 (95% CI, 0.60-0.85). When tested with adjudication as the gold standard, the LMCI still outperformed the Calandra and Cohen definitions (Îș = 0.65 [95% CI, 0.60-0.70] vs Îș = 0.29 [95% CI, 0.24-0.33], respectively). CONCLUSIONS The LMCI is useful criterion of infection that is intended for sepsis research, in and outside of the ICU. Useful criteria for infection have the potential to facilitate more comparable sepsis research and exclude sepsis mimics from clinical studies, thus improving and simplifying sepsis research

    Prognostic and predictive impact of stroma cells defned by PDGFRb expression in early breast cancer: results from the randomized SweBCG91RT trial

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    Purpose Predictive biomarkers are needed to aid the individualization of radiotherapy (RT) in breast cancer. Cancer-associated fibroblasts have been implicated in tumor radioresistance and can be identified by platelet-derived growth factor receptor-beta (PDGFRb). This study aims to analyze how PDGFRb expression affects RT benefit in a large randomized RT trial. Methods PDGFRb was assessed by immunohistochemistry on tissue microarrays from 989 tumors of the SweBCG91RT trial, which enrolled lymph node-negative, stage I/IIA breast cancer patients randomized to RT after breast-conserving surgery. Outcomes were analyzed at 10 years for ipsilateral breast tumor recurrence (IBTR) and any recurrence and 15 years for breast cancer specific death (BCSD). Results PDGFRb expression correlated with estrogen receptor negativity and younger age. An increased risk for any recurrence was noted in univariable analysis for the medium (HR 1.58, CI 95% 1.11–2.23, p = 0.011) or PDGFRb high group (1.49, 1.06–2.10, p = 0.021) compared to the low group. No differences in IBTR or BCSD risk were detected. RT benefit regarding IBTR risk was significant in the PDGFRb low (0.29, 0.12–0.67, p = 0.004) and medium (0.31, 0.16–0.59, p < 0.001) groups but not the PDGFRb high group (0.64, 0.36–1.11, p = 0.110) in multivariable analysis. Likewise, risk reduction for any recurrence was less pronounced in the PDGFRb high group. No significant interaction between RT and PDGFRb-score could be detected. Conclusion A higher PDGFRb-score conferred an increased risk of any recurrence, which partly can be explained by its association with estrogen receptor negativity and young age. Reduced RT benefit was noted among patients with high PDGFRb, however without significant interaction.publishedVersio

    Progress towards a Nordic standard for the investigation of hematuria: 2019

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    Objective: To describe the management of patients with hematuria in the Nordic countries in relation to bladder cancer epidemiology, especially in the context of introducing fast track pathways with the aim of proposing a common guideline.Materials and methods: Epidemiological data on bladder cancer from each country, and the combined cancer registry, Nordcan, were analyzed. The evolution of the different national recommendations and the introduction of fast track pathways were assessed. Patients' demographics, type of hematuria and cancer detection rates were analysed if available.Results: The crude incidence of bladder cancer has increased substantially since the 1960s, while the age standardized incidence has been stable during recent decades. The relative survival has increased in all countries, while the mortality has been stable. For those with microscopic hematuria there has been a clear trend towards less rigorous investigations. In the fast track pathways, introduced in three of five countries, about one in five patients with macroscopic hematuria had a cancer diagnosis. Data show that time to diagnosis has been reduced.Conclusions: The number of patients with bladder cancer is increasing in the Nordic region. The introduction of fast track pathways has been important in improving the management of patients with suspicion of the disease. Our recommendation is to focus on macroscopic hematuria in the fast track pathways. Microhematuria without any symptoms should not be an indication for cystoscopy. However, urinary tract symptoms accompanied by microhematuria can still be investigated according to respective guidelines but not necessarily within fast track pathways.</p

    Skewed distribution of proinflammatory CD4+CD28null T cells in rheumatoid arthritis

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    Expanded populations of CD4+ T cells lacking the co-stimulatory molecule CD28 (CD4+CD28null T cells) have been reported in several inflammatory disorders. In rheumatoid arthritis, increased frequencies of CD4+CD28null T cells in peripheral blood have previously been associated with extra-articular manifestations and human cytomegalovirus (HCMV) infection, but their presence in and contribution to joint manifestations is not clear. In the present article we investigated the distribution of CD4+CD28null T cells in the synovial membrane, synovial fluid and peripheral blood of RA patients, and analysed the association with erosive disease and anti-citrullinated protein antibodies. CD4+CD28null T cells were infrequent in the synovial membrane and synovial fluid, despite significant frequencies in the circulation. Strikingly, the dominant TCR-VÎČ subsets of CD4+CD28null T cells in peripheral blood were often absent in synovial fluid. CD4+CD28null T cells in blood and synovial fluid showed specificity for HCMV antigens, and their presence was clearly associated with HCMV seropositivity but not with anti-citrullinated protein antibodies in the serum or synovial fluid, nor with erosive disease. Together these data imply a primary role for CD4+CD28null T cells in manifestations elsewhere than in the joints of patients with HCMV-seropositive rheumatoid arthritis

    Protein C Inhibitor—A Novel Antimicrobial Agent

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    Protein C inhibitor (PCI) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins. Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens. This ability is mediated by the interaction of PCI with lipid membranes, which subsequently leads to their permeabilization. As shown by negative staining electron microscopy, treatment of Escherichia coli or Streptococcus pyogenes bacteria with PCI triggers membrane disruption followed by the efflux of bacterial cytosolic contents and bacterial killing. The antimicrobial activity of PCI is located to the heparin-binding site of the protein and a peptide spanning this region was found to mimic the antimicrobial activity of PCI, without causing lysis or membrane destruction of eukaryotic cells. Finally, we show that platelets can assemble PCI on their surface upon activation. As platelets are recruited to the site of a bacterial infection, these results may explain our finding that PCI levels are increased in tissue biopsies from patients suffering from necrotizing fasciitis caused by S. pyogenes. Taken together, our data describe a new function for PCI in innate immunity

    Studies on the host response to infection in the circulatory system

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    Sepsis is a heterogeneous, dynamic, and complex syndrome caused by interaction between the host and the invading pathogen. It is associated with an overwhelmingly dysregulated immune response, and also immunosuppression. In spite of our improved understanding of the underlying molecular pathology, sepsis still remains a common cause of morbidity and mortality worldwide. This is reflected in the unsatisfying results obtained from numerous clinical sepsis trails and in the fact that there is no sepsis-specific treatment available today. It has been proposed that it is time to reconsider the concept of sepsis and to develop novel approaches to the study of severe infectious diseases. The main goal of this thesis was to study host-pathogen interactions in the circulatory system. The research strategy pursued consisted of two distinct parts. Firstly, I worked on elucidating individual host-pathogen interaction mechanisms regarding the close crosstalk between coagulation and the innate immune system. Secondly, I used state-of-the art mass spectrometry analysis in order to get a holistic overview of the molecular processes associated with the pathogenesis of sepsis. In the first two papers, we investigated mechanisms of host-pathogen interaction while focusing on two proteins: tissue factor (TF) and protein C inhibitor (PCI). Paper I showed that soluble M1 protein from Streptococcus pyogenes induces TF expression on monocytes and pro-coagulant activity in whole blood. Paper II demonstrated a novel antimicrobial agent, PCI, and revealed a novel mechanism for how the coagulation system participates in the host defense against bacteria. In the second part of my thesis work, I used mass spectrometry (MS) to study three different biological systems: an individual cell type, clinical plasma samples, and a mouse infection model. The aim here was to develop a testable system that would enable us to study, modify, and evaluate putative effector molecules involved in the pathogenesis of sepsis. In manuscript III, I used several mass spectrometry-based techniques to study the neutrophil proteome under conditions of health and disease, and thereby identified a neutrophil-derived protein abundance pattern in plasma samples from sepsis patients. In manuscript IV, I used SWATH-MS to generate a digital compendium of data from blood plasma samples at different stages of sepsis. This study had two important novel contributions: a deep proteome map of plasma protein dynamics during severe infections and a valuable digital data resource for future sepsis research. In manuscript V, we set out to determine the dynamic changes in protein expression in mouse plasma during severe infection and compared the results to those in human sepsis plasma, with a view to facilitating transfer and interpretation of experimental observations between the two biological systems. The two research strategies used in this thesis were complementary, since the first part provided molecular details of individual biological mechanisms and the other part gave an integrated molecular overview of many separate biological events. The use of mass spectrometry-based techniques allows us to study and integrate information from in-vitro experiments, in-vivo model systems, and clinical observations. The work described in this thesis has hopefully laid the foundation for a resource that may facilitate and improve future research on sepsis

    Orsaker varför folk besöker biografer idag och i framtiden

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    Detta examensarbete handlar om biobranschen i Finland. Syftet med studien Ă€r att undersöka vilka faktorer som pĂ„verkar folk att besöka biografer idag och i framti-den. Bland annat följande frĂ„gor diskuteras och undersöks: Varför besöker folk bio-grafer? Hur ofta kommer man att besöka biografer i framtiden? Varför kunde folk tĂ€nka sig gĂ„ oftare pĂ„ bio i framtiden? I arbetet presenteras biografernas verksamhet samt deras stĂ€llning i Finland. Branschens viktiga historiska skeden presenteras frĂ„n biografernas födsel i Finland fram till Ă„ret 2015. I delen med biografernas historia diskuteras Ă€ven internets inverkan pĂ„ biobranschen. I arbetet diskuteras biografernas förĂ€ndringar pĂ„ kulturell och teknologisk nivĂ„ och deras inverkan pĂ„ branschen. I examensarbetet presenteras och analyseras en biografundersökning. Undersökning-en jĂ€mför olika gruppers konsumentbeteendeskillnader. Undersökningen analyseras och diskuteras med hjĂ€lp av figurer och tabeller med tre olika infallsvinklar per enkĂ€tfrĂ„ga. Dessa infallsvinklar handlar om eventuella skillnader mellan mĂ€n och kvinnor, olika Ă„ldersgrupper samt olika konsumentgrupper gĂ€llande deras biobesök. Även andra inverkande faktorer pĂ„ biobranschen som andra medel för filmtittande behandlas i undersökningen. PĂ„ basis av undersökningen kan man dra bland annat den slutsatsen att det finns signifikanta skillnader mellan olika Ă„ldersgrupper nĂ€r det gĂ€ller biobesök. De yngre Ă„ldersgrupperna i undersökningen anser det vara viktigare att se de nyaste filmerna dĂ„ man jĂ€mför med de Ă€ldre Ă„ldersgrupperna. Detta Ă€r bland annat en av orsakerna till varför de yngre Ă„ldersgrupperna besöker biografer.This thesis is about the cinema industry of Finland. The purpose of the thesis is to investigate why people visit cinemas today and in the future. Among other questions, these questions are discussed and investigated in the thesis: Why do people go to cinemas? How often will cinemas be visited in the future? What are the reasons for people to think they will visit cinemas more often in the future? The current situation of Finnish cinemas and their different acts are presented in the thesis. The most important phases of the Finnish cinema history is presented from the birth of cinemas in Finland all the way till the year 2015. In the history part of the thesis the effects of internet towards the cinema industry is discussed. The technological and cultural changes during the history of the culture of cinemas in Finland is discussed in the the-sis. A cinema research of consumer behavior from different consumer group aspects at cinemas is presented and analyzed. The results of the research is analyzed and demonstrated with different figures and tables of three different consumer group aspects. These aspects are about the possible differences between men and women, different age groups and different consumer groups towards the different questions in the research. Other possible effects on the cinema industry, such as other ways for watching movies, is discussed. According to the research the younger age groups think it is more important to see the latest movies when we compare to the older groups. This is one among other reasons why the younger groups visit cinemas
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