Minoische Rhyta

Detta examensarbete har genomförts vid Institutionen för produktionsekonomi på Linköpings tekniska högskola. Uppdragsgivare har varit Svenskt Näringsliv och arbetet har utförts på Södersjukhuset i Stockholm. Syftet med arbetet har varit att kartlägga flödet av patienter med sökorsak höft genom sjukhusets akutmottagning och ortopediska verksamhet, för att därefter analysera detta och föreslå åtgärder som kan minska väntetider och öka genomflödet. På akutmottagningen har tre aktiviteter visat sig vara viktigare än de övriga, nämligen läkarundersökning, röntgen och inläggning på vårdplats. Anledningen till detta är att väntan till de aktiviteterna utgör cirka två tredjedelar av en patients tid på akutmottagningen. Därför har åtgärderna på akutmottagningen syftat till att reducera dessa väntetider och mildra dess konsekvenser. Ett led i detta är att akutmottagningen anpassar antalet läkare bättre efter de varierande behoven över dygnet. Röntgenavdelningen bör kontinuerligt utvärdera behoven från akutmottagningen för att på så sätt balansera sin kapacitet. Patienter som är färdiga på akutmottagningen placeras i en separat lokal under tiden de väntar på vårdplats. Inom den ortopediska verksamheten syftar åtgärdsförslagen till en förändrad hantering av resurser och ett bättre utnyttjande av desamma. De två resurser som arbetet koncentrerar sig kring är vårdplatser och operation, och avvägningen om dessa bör vara gemensamma eller dedicerade mellan elektiva och akuta patienter. Det betydande antalet operationer som drabbas av störningar, och därför ej kan genomföras, talar för en uppdelning av operationsresurser mellan akuta och elektiva patienter. Däremot bör vårdplatserna vara gemensamma eftersom de elektiva patienterna kan jämna ut den totala efterfrågan på vårdplatser. Genom att dessutom se över utskrivningsrutinerna från vårdavdelningar kan flödet förbättras ytterligare. Åtgärder som föreslagits för att åstadkomma detta är tidig planering av utskrivningar, utskrivningskoordinator och att inrätta en lokal i väntan på hemfärd

Estniska Republikens geografi

https://www.ester.ee/record=b2067833*es

Increased aldehyde-modification of collagen type IV in symptomatic plaques - A possible cause of endothelial dysfunction.

Subendothelial LDL-adhesion and its subsequent oxidation are considered as key events in the development of atherosclerotic lesions. During oxidation of LDL, reactive aldehydes such as malondialdehyde (MDA) are formed, which modify apolipoprotein B100. However, the possibility that these reactive aldehydes could leak out of the LDL-particle and modify surrounding extracellular matrix proteins has been largely unexplored. We have investigated if aldehyde-modification of collagen type IV, one of the major basement membrane components, in plaques is associated with cardiovascular events

Circulating cytokines reflect the expression of pro-inflammatory cytokines in atherosclerotic plaques.

Inflammation is a key factor in the development of plaque rupture and acute cardiovascular events. Although imaging techniques can be used to identify vulnerable atherosclerotic plaques, we are lacking non-invasive methods, such as plasma markers of plaque inflammation that could help to identify presence of vulnerable plaques. The aim of the present study was to investigate whether increased plasma levels of pro-inflammatory cytokines reflects inflammatory activity within atherosclerotic plaques

NFAT regulates the expression of AIF-1 and IRT-1: Yin and yang splice variants of neointima formation and atherosclerosis.

Aims Alternative transcription and splicing of the allograft inflammatory factor-1 (AIF-1) gene results in the expression of two different proteins: AIF-1 and interferon responsive transcript-1 (IRT-1). Here we explore the impact of AIF-1 and IRT-1 on vascular smooth muscle cell (VSMC) activation and neointima formation, the mechanisms underlying their alternative splicing, and associations of AIF-1 and IRT-1 mRNA with parameters defining human atherosclerotic plaque phenotype.Methods and results Translation of AIF-1 and IRT-1 results in different products with contrasting cellular distribution and functions. Overexpression of AIF-1 stimulates migration and proliferation of human VSMCs, whereas IRT-1 exerts opposite effects. Adenoviral infection of angioplasty-injured rat carotid arteries with AdAIF-1 exacerbates intima hyperplasia, whereas infection with AdIRT-1 reduces neointima. Expression of these variants is modulated by changes in nuclear factor of activated T-cells (NFAT) activity. Pharmacological inhibition of NFAT or targeting of NFATc3 with siRNA lowers the AIF-1/IRT-1 ratio and favors an anti-proliferative outcome. NFAT acts as a repressor on the IRT-1 transcriptional start site, which is also sensitive to interferon-γ stimulation. Expression of AIF-1 mRNA in human carotid plaques associates with less extracellular matrix and a more pro-inflammatory plaque and plasma profile, features that may predispose to plaque rupture. In contrast, expression of IRT-1 mRNA associates with a less aggressive phenotype and less VSMCs at the most stenotic region of the plaque.Conclusions Inhibition of NFAT signaling, by shifting the AIF-1/IRT-1 ratio, may be an attractive target to regulate the VSMC response to injury and manipulate plaque stability in atherosclerosis

Immune hierarchy among HIV-1 CD8+ T cell epitopes delivered by dendritic cells depends on MHC-I binding irrespective of mode of loading and immunization in HLA-A*0201 mice

Recent human immunodeficiency virus type 1 (HIV-1) vaccination strategies aim at targeting a broad range of cytotoxic T lymphocyte (CTL) epitopes from different HIV-1 proteins by immunization with multiple CTL epitopes simultaneously. However, this may establish an immune hierarchical response, where the immune system responds to only a small number of the epitopes administered. To evaluate the feasibility of such vaccine strategies, we used the human leukocyte antigen (HLA)-A*0201 transgenic (tg) HHD murine in vivo model and immunized with dendritic cells pulsed with seven HIV-1-derived HLA-A*0201 binding CTL epitopes. The seven peptides were simultaneously presented on the same dendritic cell (DC) or on separate DCs before immunization to one or different lymphoid compartments. Data from this study showed that the T-cell response, as measured by cytolytic activity and γ-interferon (IFN-γ)-producing CD8+ T cells, mainly focused on two of seven administered epitopes. The magnitude of individual T-cell responses induced by immunization with multiple peptides correlated with their individual immunogenicity that depended on major histocompatibility class I binding and was not influenced by mode of loading or mode of immunization. These findings may have implications for the design of vaccines based on DCs when using multiple epitopes simultaneously

T-cell competition as a mechanism for immunodominance and the role for IL-12 in CTL responses

Immunodominance is a process in which the immune response focuses on one or a few of all potential epitopes that exists within an antigen. The mechanisms for immunodominance have not yet been determined. The work described in this thesis has addressed the question whether competition between peptides for presentation at the cell surface or competition between Tcells for activation by the antigen presenting cell are important mechanism for immunodominance. In an experimental model with transplantation antigens there is no detectable difference in the amount of subdominant epitopes presented at the cell surface in the presence or absence of immunodominant epitopes. In a model with synthetic peptides there is no correlation between peptide affinities for MHC class I or T-cell avidity and immunodominance. These results indicate that competition between epitopes for presentation at the cell surface is not a determining mechanism in these models. We show that the antigens need to be presented by the same cell for immunodominance to occur. We also show that immunodominance is not absolute, since mice previously inoculated with the complete antigenic barrier not only retain their capacity to respond to subdominant epitopes but they are more easily primed against subdominant epitopes indicating a passive mechanism for immunodominance that allows some printing also against subdominant epitopes. Finally, we can overcome immunodominance in both of these models by inoculation of high numbers of antigen bearing dendritic cells. Based on these results we suggest that the determining mechanism for immunodominance in these models is T-cell competition. T-cells may compete for cytokines such as IL-12, access to the APC itself for costimulation or any other factor provided by the APC. The second part of this thesis concerns the role for interleukin-12 in the immune response against tumors and for the initiation of primary and memory CTL responses against synthetic peptide antigens. IL-12 is an important cytokine that promotes cellular immunity mainly by the induction of interferon-gamma production. IL-12 also augments the cytotoxic ability of both natural killer cells and cytotoxic T-lymphocytes. We have shown that IL-12 is important for the generation of innate immune responses against a TAP deficient lymphoma (RMA-S) as well as adoptive immunity against the TAP expressing lymphoma (RMA). We also show that IL-12 is important for the generation of CTL responses against synthetic peptides pulsed on dendritic cells. The need for IL-12 can be circumvented by immunization with peptides together with adjuvant. Interestingly, IL-12 seems to be important for the initiation of CTL memory responses also in mice immunized with adjuvant. Once a memory response has been established IL-12 is no longer needed for maintenance of that response

Riskbedömning och riskhantering i samband med vägbyggen

The aim with this thesis is to investigate the risk management at the department Road construction, The National Road Administration Region Mälardalen. The aim is also to study how the risk management could be improved to better support the project leaders. Included in theses aims is to examine potential problems with the current risk management and to suggest changes. It is of utter importance to define the concept of risk, to study how risk can be measured and in which ways risk can be analyzed. In doing so, a literary study has be done and fourteen respondents has been interviewed. Risk is to be seen more as a concept than a quantity. Risk management demands time and money. It takes some effort to perform the initial brainstorm and the constant revision. However, risk management can lead to saved costs and the avoidance of accidents. To keep a list of risks is not a waterproof method, nevertheless it is better to create an awareness of risk than ignore a method for its flaws. Risk management can create a discussion about problems and difficulties, a discussion that might otherwise not have a forum