The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN

Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques

BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques

Memoir in transit : whiteness, displacement and journalism in Peter Godwin's autobiographical writing

This dissertation is an examination of Peter Godwin’s three autobiographical works that relate to his life in Rhodesia/Zimbabwe: Mukiwa: A White Boy in Africa (1996), When a Crocodile Eats the Sun (2006) and The Fear: The Last Days of Robert Mugabe (2010). The memoirs raise questions relating to white Zimbabweanness, displacement, and the legacy of the colonial period. Controversy inevitably surrounds them as they are the literary products of descendants of settlers. A number of similar memoirs have been published since the land reform in 2000. Representing the nation in literature and writing specific versions of history emerge as problematic aspects of this literature. Most of the writers no longer live in Zimbabwe and they often write for an Anglo-American audience. Godwin’s memoirs forge a new tradition of white Zimbabwean literature, one strongly preoccupied with discourses of childhood, nostalgia, and loss. He also goes beyond such notions in his writing and a clear development is visible in his memoirs, which makes a study of them worthwhile. The three memoirs occupy themselves to a large extent with history, politics and also personal identity. Having been born to European settlers, Godwin’s complex position as a white Zimbabwean is cause for much grief and pain, and also confusion with regard to his past, present and future. The results of the analysis show that the complexity of Godwin’s memoirs allows for a thorough investigation of this genre of writing and enable going beyond previous studies and criticism. My analysis also points to problems in the theoretical framework, for example with regard to various concepts such as diaspora, which is often too broadly used and defined. This study of Godwin’s memoirs also brings forth questions about the future of postcolonial literature, where African literature is going and what defines it, as well as autobiography’s role as mediator between the past and the present. This is a central struggle in Godwin’s writing, one which also includes the difficult balancing act between the personal and the professional dimensions of his life

Influenza A virus, H10N4, naturally pathogenic for mink (Mustela vison)

The thesis summarizes and discusses the results from studies of an influenza A virus isolated from an outbreak of pneumonia among farmed mink in Sweden. This new disease in mink was described based on clinical, serological, and pathological investigations, and the causality established by experimental infection of mink. The virus was identified and named A/mink/Sweden/84 (H10N4). Serological investigations showed that this virus was not present in mink in other areas of the country. A direct transmission of virus from birds to mink was suggested, since the subtypes H10 and N4 had previously only been isolated from birds. The genetic relationships between the mink virus and three avian derived influenza viruses of subtype H10 were analyzed by oligonucleotide mapping. The mink virus was shown to be closely related to two avianderived H10N4 viruses and less related to the prototype avian H10 strain, A/chicken/Germany/49 (H10N7). Experimental infection of mink with these four H10 influenza strains showed that all four viruses stimulated an antibody-mediated immune response. All three H10N4 viruses also caused clinical disease in mink and spread through contact, whereas the H10N7 virus only caused mild lung lesions but no clinical disease or contact transmission. Experimental aerosol infection of mink was used to study the early lesions in the respiratory tract caused by the H10N4 virus from mink and the prototype avian H10 virus. Through immunohistochemistry, morphometrical analysis of the pneumonia, histopathology and virus culture, marked differences in pathogenicity were observed between the two viruses. The H10N4 virus was reisolated from all infected mink, whereas no H10N7 virus could be reisolated. Both viruses caused a bronchointerstitial pneumonia in the infected mink. However, the spread of the virus within the respiratory tract and the area density of pneumonia peaked on day two for the H10N7 virus, whereas the H10N4 virus from mink continued to spread all through the one-week observation period, ultimately killing one of the infected mink on day seven. An additional study indicated that the differences in virus spread in vivo could be modelled in vitro in mink lung-cell cultures

Jämnårigsocialisation i svensk skola

Peer group socialization in Swedish schools. This study examines the significance of peers in the process of socialization in Swedish schools, that is to say, the mutual influence that children and young people exert on each other. It analyses how peer group socialization is apprehended and evaluated in curricula for Sweden’s comprehensive schools and in related research. Part One defines the object of study more precisely by relating it to socialization research. In this part of the thesis, research on the socialization of children and young people is reviewed and some central concepts that can serve to characterize peer group socialization are distinguished: friendship, peer group membership and youth socialization. In addition, the school is considered as a potential place of encounter for peers. Part Two consists of a systematic comparison of how different conceptions of peer group socialization have been expressed over time in curricula and in research on schooling. Three different periods with three more or less dominant conceptions of the significance of the peer group for socialization are identified: I. The potential of the school to create peer group community is formulated. II. The potential of peer group socialization is neglected. III. The potential of peer group socialization is rediscovered. During the first period, peer group socialization as a means of creating community is prominent in the 1962 comprehensive school curriculum (Lgr 62) and in the official studies and schools research preceding it. In the 1969 curriculum (Lgr 69), perceptions change. Researchers are more ambivalent to the peer group and there is somewhat less confidence in its positive potential to foster community. The second period is characterized by a neglect of the peer group’s potential to create community, first in the 1980 curriculum (Lgr 80) and later in that of 1994 (Lpo 94). In research on schools and youth, the peer group is represented primarily as a force that seeks to contest the culture of schools. In the third period, a tendency to rediscover peer group socialization can be observed in official studies carried out after Lpo 94. In schools research, attention is drawn to the possible contribution which the peer group can make to learning. Some youth researchers express confidence in the peer group’s potential as a positive, community-creating force, but at the same time there are those who see peer group socialization as risky and a source of problems. There may possibly be a positive community-creating force in peer group socialization that has been overlooked. All things considered, the author ventures to suggest that the community-creating potential of the peer group is an inadequately explored perspective in Swedish research on schooling, a perspective that could enable us to see the possibilities in schools, rather than the problems

Validitet och reliabilitet av ett arbetsbelastningsindex (AI) i en FHV enkät

Abstract   The purpose of this work was to scientifically evaluate the sustainability of parts of  a company-specific survey within the Occupational Health Services (FHV). The service is called HALU which is an abbreviation of the “Work Health and Lifestyle” survey and provided by Feelgood AB. HALU is a questionnaire that is used frequently towards the customer and answered on an individual level with subsequent health interviews and a statement regarding the organization's performance in order to identify the health, lifestyle and working situation of the organization. In this work, questions regarding workloads were evaluated. There were six different workload questions, and the question in this paper were whether these issues had an internal consistency, validity and reliability, and if these issues’ correlation to questions about health during the past year. These analyzes were designed as cross-sectional studies The work also included a longitudinal study in which survey responses from the same individual on two occasions analyzed to see if the responses of workload and health has correlation at two different response times. The material used is a selection from Feelgood database from which includes total includes 130,422 HALU surveys. This sample includes 17,513 surveys from 201007. The study was performed in three steps: Step 1 was a reliability study in which the internal consistency analysis regarding workload questions in the questionnaire . A workload index was created (AI) Stage 2 was a validity study where the correlation coefficient analyzed for correlation between the AI which was calculated in step 1 and the in -depth study of health issues. Step 3 was also a validity study where the correlation coefficient was analyzed in terms of relationships between different survey occasions in the same individual, in order to see if the change in workload results in change in self-perceived health . The result showed that there was strong internal consistency regarding workload issues and that there was correlation between workload and health in a cross section . There were also correlation between survey responses occasions but this was low.Syftet med detta arbete var att på ett vetenskapligt sätt utvärdera hållbarheten i delar av enföretagsspecifik tjänst inom Företagshälsovården FHV. Tjänsten heter HALU vilket är en förkortning av Hälso Arbetsmiljö och Livsstilsundersökning och tillhandahålls av Feelgood AB. HALU är en enkät som används frekvent ut mot kund och besvaras på individnivå med efterföljande hälsosamtal och en sammanställning beträffande organisationens resultat i syfte att kartlägga hälsa, livsstil och arbetsmiljöläget för organisationen. I detta arbete har frågor gällande arbetsbelastning utvärderats. Validiteten och reliabiliteten i detta index har analyserats. Indexet består av 6 frågor. Arbetet innefattar dels en tvärsnittstudie men även en longitudinell studie där enkätsvar från samma individ vid två tillfällen analyserades i syfte att se om svaren från arbetsbelastning och hälsa hade korrelation vid två olika svarstillfällen. Materialet som användes var ett urval  från Feelgoods databas vilken innefattar totalt 130.422  HALU enkäter. I detta urval ingick 17.513 enkäter från juli 2010 Studien gjordes i tre steg: Steg 1 är en reliabilitetsstudie där den interna konsistensen analyseras vad beträffar arbetsbelastningsfrågorna i enkäten. Ett arbetsbelastningsindex skapades (AI). Steg 2 är en validitetsstudie där korrelationskoefficienten analyserades beträffande samband mellan AI som räknades fram i steg 1 och de i studien ingående hälsofrågorna. Steg 3 är även det en validitetsstudie där korrelationskoefficienten analyserades vad gäller samband mellan olika enkättillfällen hos samma individ, i syfte att se om förändring i arbetsbelastning resulterade i förändring i självupplevd hälsa. I både steg 2 och 3 är det Begreppsvaliditet (construct validity) som mäts. Resultatet visar att det finns stark internkonsistens beträffande arbetsbelastningsfrågorna, det vill säga att dessa frågor mäter arbetsbelastning. Det finns även en korrelation mellan arbetsbelastning och hälsa vid ett tvärsnitt, om skattningen av arbetsbelastningen ökar påverkas svaren på hälsofrågorna negativt. Det rådde även svag korrelation mellan de olika enkätsvarstillfällena.

Marknadsföring av begåvningar inom musikbranschen

Uppsatsen behandlar hur skivbolagen väljer att marknadsföra begåvningar/egenskaper hos en artist. Undersökningen bygger på en kvalitativ studie där sex mindre fallstudier inkluderades. De sex artister/grupper som studerats innefattade valen av marknadsföring vid lanseringen, begåvning samt varumärkesbyggande. I undersökningen har alla använt sig efter det som kallas ett planerat angreppssätt, vilket går ut på att ha en strategisk plan på hur de skall marknadsföra artisterna/grupperna för att uppnå störst möjlig effekt. För att påverka konsumenterna väljer skivbolagen att sammansätta marknadsföringsinsatserna efter benämningen i referensramen, marknadsföringsmaskinen. Beroende på artist och genre, egenskaper och begåvningar sammansätts marknadsförings-maskinen olika. Förekommande media är radio, scenuppträdande och press. Vidare behandlas hur skivbolagen arbetar med att bygga varumärken och skapa värdet till produkten. Det första steget innebär att etablera artisten/gruppen med ett igenkänt namn. Det är först när namnet är etablerat som värdet på artisten kan skapas genom kollektivets erkännande. Även arbetet med att skapa varumärket har skett på differentierade sätt i de sex olika fallen. Begåvning är ett komplext och svår definierat begrepp, där varje individ har sin definition av ordet begåvning. Gemensamt är dock att begåvning anses vara en positiv avvikelse från det som anses normalt. Begåvningar hos artisterna/grupperna i undersökningen har varit karisma, utstrålning, röst, förnuftiga åsikter och utseende. Flera av dem var även begåvningar vid framställandet av musikaliskt material och textskrivande. Att få kollektivet att skapa värde i artisten och musiken innebär olika val för skivbolagen av exponering. Beroende på varje unik individ väljer skivbolagen en sammansättning av de val som finns att tillgå, för att skapa det svåra, betydelsefulla och komplexa, värdet. Nyckelord Skivbolag, artist, begåvning, marknadsföringsmaskin, värde

Corporate Social Responsibility. Varför företagen tar ett ökat ansvar i samhället

Företagens sociala ansvarstagande, det vill säga Corporate Social Responsibility (CSR), är ett aktuellt ämne som ofta diskuteras och uppmärksammas i såväl medier som också hos företagsledare. Det kan finnas flera förklaringar till att företag väljer att ta ett frivilligt ansvar. För att kunna få en fördjupad förståelse för företagens samhällsengagemang är det därför angeläget att identifiera vilka drivkrafter som ligger bakom ett CSR-arbete. Syftet är att beskriva varför de undersökta företagen arbetar med CSR samt att identifiera de främsta drivkrafterna bakom de undersökta företagens CSR-arbete. Studien baseras på en kvalitativ insamlingsmetod i form av telefonintervjuer. Det för att erhålla djupare förståelse för varför företag arbetar med CSR. Intervjuerna hade en semistrukturerad karaktär och genomfördes med respondenter från sex företag, vilka samtliga bedriver ett aktivt CSR-arbete. Urvalet av företagen har skett utifrån det brittiska analysföretaget Innovests lista över de 100 mest hållbara företagen i världen 2007, företagsnätverket CSR Sweden, förslag från CSR-konsulten Ola Löhman samt webbplatsen CSR i Praktiken.se. I studien framkommer det att det finns flera anledningar till att företagen arbetar med CSR. Ett skäl till att företagen engagerar sig i CSR-frågor är, enligt studien, det etiska ansvarstagandet. Samhällets och intressenternas krav att agera etiskt gör att företag måste ta hänsyn till dessa för att undvika att bli anklagade för ett oetiskt handlade. Det då ett oetiskt agerande kan innebära långsiktiga negativa effekter för företaget, som exempelvis ett försämrat rykte och minskad attraktivitet hos intressenterna. Studien visar således att intressenterna har en viktig roll i företagens CSR-arbete genom deras behov och krav på företagens verksamheter. Därmed är vårdandet av relationerna till intressenterna en anledning till att företagen väljer att arbeta med CSR. Vidare kopplar företagen image och rykte till varumärket, som stärks genom deras sociala och miljömässiga ansvarstagande. Att varumärket stärks genom CSR-aktiviteter är därmed ytterligare en drivkraft som framkommer i studien. De främsta drivkrafterna som har identifierats hos de undersökta företagen är lönsamhet, riskhantering, varumärket, medarbetare och långsiktigt tänkande. Det kan därför konstateras att företagen i första hand arbetar med CSR för att det har en positiv påverkan på företaget och inte för de positiva följderna det har för samhället i stort.Corporate Social Responsibility (CSR) is a frequently discussed subject, therefore Media and business managers are paying close attention to the social and environmental responsibility of the companies. There can be many different driving forces behind the voluntary CSR activities. To reach a deeper understanding of the companies’ social and environmental commitment it is important to identify the reasons behind incorporating CSR regulations. The purpose of the study is to describe why the companies in the survey work with CSR and to identify the prime reasons behind integrating CSR activities into their business operations. The study is based on a qualitative method using telephone interviews. The method allowed for a deeper comprehension of why companies work with CSR. The interviews were semi-structured and based on the respondents from six companies. All the companies followed CSR guidelines. The companies were chosen from Innovests’ list of 100 most sustainable companies in the world of the year 2007, the company network CSR Sweden, proposal from the CSR consultant Ola Löhman and the website CSR I Praktiken.se. The study demonstrates several reasons why the companies work with CSR. One reason, according to the study, is ethical responsibility. The companies have to consider the impact of the stakeholders and society on behaving ethically. Acting unethically can lead to long-term negative consequences, such as a bad reputation and decreased attractiveness to the stakeholders. The study shows that the stakeholders' demands and needs influence how the companies work with CSR. A good relationship to the stakeholder, therefore, is one of the driving forces behind the companies' CSR activities. Furthermore, the companies connect their image and reputation to their brand, which is strengthened when they take-on social and environmental responsibility. The prime reasons that were identified in the survey are profitability, risk management, employees, long-term thinking and the brand. Therefore, the conclusion is the companies in this survey are working with CSR because it influences the company in a positive manner and not because they want to benefit society at large

Critical Link 4 Professionalisation of interpreting in the community. Selected papers from the 4th International Conference on Interpreting in Legal, Health and Social Service Settings, Stockholm, Sweden, 20-23 May 2004

In this presentation I will first briefly describe the Swedish community interpreting scene and its historical background. Secondly, I will outline the various currently existing training opportunities for interpreters. Interpreter training, both at university level and in vocational courses, has been instrumental in developing professionalism and creating standards for quality interpreter services. The third and last part of the paper describes initiatives in promoting professionalism not only among interpreters but also among trainers of interpreters.The Critical Link 4 -- Editorial page -- Title page -- LCC data -- Table of contents -- Acknowledgments -- References -- Foreword: Interpreting professions, professionalisation, -- I. Critical linking up -- Critical linking up: Kinship and convergence in interpreting studies -- II. Interpreters on duty in interaction: Studies of micro dynamics -- The interpreter in multi-partymedical encounters -- Interpreting in asylum hearings: Issues of saving face -- Conversational dynamics as an instructional resource in interpreter-mediated technical settings -- A data driven analysis of telephone interpreting -- III. Interpreters in the community: Studies of macro dynamics -- Interpreter-mediated police interviews: Working as a professional team -- Community interpreting in Poland -- Alternative futures for a National Institute of Translation: A case study from Malaysia -- The interpreter's 'third client': Interpreters, professionalism and interpreting agencies -- IV. Developing local standards -- The Swedish system of authorizing interpreters -- Establishment, maintenance and development of a national register -- From Aequitas to Aequalitas -- The California Standards for Healthcare Interpreters -- V. Professional ideology: Food for thought -- Professionalisation of interpreting with the community -- "Why bother?": Institutionalization, interpreter decisions,and power relations -- The interpreter as advocate: Malaysian court interpretingas a case in point -- Professionalisation of interpreters: The case of mental health care -- Professional stocks of interactional knowledge in the interpreter's profession -- Aristotelian ethics and modern professional interpreting -- VI. Improving and assessingprofessional skills: Training initiatives and programmes -- Formative assessment: Using peer and self-assessmentin interpreter trainingInterpreter internship program: Forging employer-community partnerships -- On-line and between the lines: The internet and glossary production for publicservice interpreters -- Interpreter training from scratch -- On-line and between the lines: The internet and glossary production for publicservice interpreters -- Interpreter training from scratch -- From helpers to professionals: Training of community interpreters in Sweden -- Index -- The series Benjamins Translation LibraryIn this presentation I will first briefly describe the Swedish community interpreting scene and its historical background. Secondly, I will outline the various currently existing training opportunities for interpreters. Interpreter training, both at university level and in vocational courses, has been instrumental in developing professionalism and creating standards for quality interpreter services. The third and last part of the paper describes initiatives in promoting professionalism not only among interpreters but also among trainers of interpreters.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries

Traumatic Peripheral Nerve Injuries : Experimental Models for Repair and Reconstruction

Peripheral nerve injuries are difficult to treat, and the clinical outcome after surgical repair and reconstruction is still insufficient, particularly concerning recovery of sensory function. To improve the clinical treatment strategies, experimental models are used to systematically examine the mechanisms behind nerve regeneration and assess the improvement of nerve regeneration by introduction of new surgical nerve repair and reconstruction methods (e.g., novel devices made by bioartificial materials). Rat models, where the sciatic nerve has essentially a similar size as a human digital nerve, are widely used to evaluate nerve regeneration with the inherent advantages and disadvantages of the experimental models. Estimations revealing that a large number of diabetic patients will eventually suffer from peripheral nerve injury have motivated development of suitable experimental diabetes models for studying the nerve regeneration process and novel treatment approaches. We have successfully used the Goto-Kakizaki rat model, which shows moderately increased blood sugar closely resembling type 2 diabetes, for assessing the surgical peripheral nerve regeneration potential with and without artificial scaffolds. In order to improve outcome after repair and reconstruction of nerve injuries, one has to have a clear concept concerning how to evaluate novel repair and reconstruction techniques in experimental models before clinical studies can be initiated in an accurate way