COVID-19 pandemic has exposed both strengths and weaknesses in world communities and particularly put a severe strain on health care. It is widely accepted that lifestyle factors are an important piece of the puzzle in preventive work against infectious diseases. One of these lifestyle factors is physical activity (FA) that positively affects people's well-being and has a strengthening effect on, among other things, the immune system. The purpose of the study was to investigate how people that have had SARS-CoV-2 infection describe their FA level and general state of health before the illness and how they feel that it has affected their disease course. A total of 10 semi-structured interviews were conducted during the period FebruaryMarch, which were then interpreted using content analysis as a tool. During the analysis work three main categories were identified: Well-balanced FA level, Relatively good general health, Experience of COVID-19 and FA significance. Most respondents perceived themselves as physically active to a greater or lesser extent. Respondents' perception indicates that FA has an important role in facing COVID-19 disease. Results indicate an increasingly accepted view in research that FA can act as a protective factor against SARS-CoV-2 virus / <p>Betyg i Ladok 220613.</p>

京都大学 / 新制・課程博士 / 博士(医科学) / 甲第25202号 / 医科博第158号 / 新制||医科||10(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 川口 義弥, 教授 波多野 悦朗, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

This study examines the factors to consider in establishing an effective tax Ombudsman in South Africa. It seeks to establish how the democratic protection institutions such as the South African Public Protector and the South African Human Rights Commission and the Courts created in terms of the 1996 Constitution vis-à-vis the ways the South African Revenue Service‟ (hereinafter referred to as SARS) new court rules and Service Monitoring Offices safeguard and protect taxpayers rights against SARS‟ administrative abuses. The researcher reviews and analyses literature gathered from the following sources: the Australian and Canadian tax Ombudsman, the United Kingdom‟s tax adjudicator, the South African motor industry Ombudsman, the South African banking services Ombudsman, the South African Public Protector, the Tax Administration Act (28 of 2011) (hereinafter referred to as the TAA), the South African Constitution (108 of 1996), and other popular scientific articles and reports on the introduction of the tax Ombudsman in South Africa. The findings reveal the core factors that underscore the establishment of an effective tax Ombud in South Africa to include: independence, neutrality, credible review process and confidentiality. Other auxiliary factors with regard to the appointment of the tax Ombud are: leadership skills, honesty, integrity and courage. Furthermore, the provisions of the TAA, in relation to the appointment of the tax Ombud‟s funding, staffing, location, and powers with particular reference to cost recovery and disclosure of taxpayers‟ confidential information, impede on the tax Ombud‟s independence. It also emerged from this study that the independence of the tax Ombud‟s office is being over-emphasised, leaving other pertinent issues of equal importance, such as education and publicity, unattended to. The recommendations for this study revolve on the tax Ombud‟s appointment, budget and recruitment of its own staff, building a reputation of independence through public education and the power to recover costs. / MCom (South African and International Taxation), North-West University, Potchefstroom Campus, 2014

This study examines the factors to consider in establishing an effective tax Ombudsman in South Africa. It seeks to establish how the democratic protection institutions such as the South African Public Protector and the South African Human Rights Commission and the Courts created in terms of the 1996 Constitution vis-à-vis the ways the South African Revenue Service‟ (hereinafter referred to as SARS) new court rules and Service Monitoring Offices safeguard and protect taxpayers rights against SARS‟ administrative abuses. The researcher reviews and analyses literature gathered from the following sources: the Australian and Canadian tax Ombudsman, the United Kingdom‟s tax adjudicator, the South African motor industry Ombudsman, the South African banking services Ombudsman, the South African Public Protector, the Tax Administration Act (28 of 2011) (hereinafter referred to as the TAA), the South African Constitution (108 of 1996), and other popular scientific articles and reports on the introduction of the tax Ombudsman in South Africa. The findings reveal the core factors that underscore the establishment of an effective tax Ombud in South Africa to include: independence, neutrality, credible review process and confidentiality. Other auxiliary factors with regard to the appointment of the tax Ombud are: leadership skills, honesty, integrity and courage. Furthermore, the provisions of the TAA, in relation to the appointment of the tax Ombud‟s funding, staffing, location, and powers with particular reference to cost recovery and disclosure of taxpayers‟ confidential information, impede on the tax Ombud‟s independence. It also emerged from this study that the independence of the tax Ombud‟s office is being over-emphasised, leaving other pertinent issues of equal importance, such as education and publicity, unattended to. The recommendations for this study revolve on the tax Ombud‟s appointment, budget and recruitment of its own staff, building a reputation of independence through public education and the power to recover costs. / MCom (South African and International Taxation), North-West University, Potchefstroom Campus, 2014

【研究緣起與問題】2003年春季，SARS在全球造成一陣轟動，同時也重創全球的經濟，如今SARS會不會再來？政府如何因應？政府如何監測疫情？如何防治疫情？如果SARS等新興及再浮現感染症 （Emerging and Re-emerging Infectious Diseases）出現時，負責全國傳染病防治任務的行政院衛生署疾病管制局是如何作好全國傳染病防治工作呢？中央及地方主管機關之溝通，如何共同消除指責與誤會，發揮團隊精神，如何共同作好全國傳染病防疫任務，爭取公眾對政府之瞭解並加以支持，同時防止任何可能之攻擊，才是全民之福祉。故以「全國傳染病通報系統」的績效，其所仰賴之溝通通路之問題研究，是本研究的動機。了解「傳染病通報管理系統(WEB版)」最大的問題及新興傳染病（如SARS）防治通報的問題及「傳染病通報管理系統」最需要改進之的地方，是本研究的目的。 【研究方法與資料】本研究採取量化與質化並重的方法，以網路問卷方式的進行問卷調查，問卷對象為全國使用傳染病通報管理系統之相關人員，問卷問題內容的設計主要的型式含有開放式問卷（Open –Ended Question）、封閉式問卷（Close-Ended Question）及混合型問卷（Mixed Question）三種。同時以九十二年針對新興傳染病SARS期間為例，深度訪談當時任職於中央與地方負責傳染病防治權責具代表性者五位主管進行訪談，瞭解受訪者對新興傳染病如SARS防治的問題及「傳染病通報管理系統」最需要改進之的地方，以彌補問卷調查法無法深入瞭解到問題之缺點。 【研究結論與建議】 一、根據筆者初步研究經問卷的實證調查之後，從問卷分析資料顯示，使用者使用電腦的時間愈久，對以新版為溝通工具滿意度愈低；而愈瞭解通報系統的使用者，其以新版為溝通工具滿意度愈高，愈滿意新版改進之電腦網路溝通效果。顯示新版的通報系統在設計的操作介面與程序上，沒有人性化，作業內容繁多、需輸入的項目、資料太繁瑣、版面太繁瑣等，反而徒增使用者的困擾；而愈瞭解通報系統的使用者，其對新版的滿意度越高，表示對於使用者在操作上的教育訓練仍須加強，才能發揮新版通報系統的成效。 二、從敘述統計分析中發現： 受訪者對「訊息異動通知作業流程滿意」的使用滿意度的平均數最高，平均數為2.8095表示：較為滿意。「通報作業流程滿意嗎」的使用滿意度的平均數最低，平均數為2.3934，受訪者表示：較為滿意。以新版為溝通工具整體溝通滿意情形，平均數為2.558滿意。 三、開放式問卷分析資料顯示，花太多時間、速度太慢、網路的頻寬過窄又不穩定或無法登錄、作業內容繁多、作業流程問題、資訊管理問題及功能增添與建議等部分。 四、根據筆者初步研究深度訪談之後，彙整中央主管機關及地方主管機關的訪談核心二部分的問題與建議。 五、研究建議： 綜合問卷調查及深度訪談結果，提出政策層面、組織溝通層面、管理層面、實務操作層面等之建議。 【關鍵字】傳染病通報系統、嚴重急性呼吸道症候群(severe acute respiratory syndrome, SARS)、組織溝通、溝通通路、行政院衛生署疾病管制局 / 【Background and Issues】 In the spring of 2003, SARS outbreaks devastated the whole world; they also heavily damaged the world economy. Will SARS come back? How can governments manage it? How can government monitor the epidemics? How can we control the infection? When emerging and re-emerging infectious diseases such as SARS appear, how can the Center for Disease Control of the Department of Health, an organization in charge of national disease control, plan and execute measures for the control of communicable diseases? Effective communication between the central and the local competent authorities to remove together blames and misunderstanding, to develop team spirit, to attain jointly the goal of disease control, to solicit understanding and support of the public to the government, and to prevent any likely attack are some of the considerations in improving the welfare of the public. The reason of the present study was to understand, through the achievements thus far of the National Communicable Disease Reporting System, issues involved in the communication channels. The purposes of the study were to understand the major problems of the Communicable Disease Reporting and Management System (the Web version), issues involved in the reporting of emerging infectious diseases, and areas of the Communicable Disease Reporting and Management System where improvement was most urgently needed. 【Method and Materials】 Both the quantitative and qualitative methods were used. Questionnaire interview was conducted through the web to persons using the Communicable Disease Reporting and Management System throughout the country. The questionnaire contained open-end questions, closed-end questions and questions of mixed types. At the same time, to understand in depth areas not properly covered by the questionnaire interview, five key persons responsible for disease control at the time of the SARS outbreaks in 2003 at the central and the local levels were interviewed to understand their attitudes toward the control of emerging infectious diseases such as SARS, and the improvement most urgently needed for the Communicable Disease Reporting and Management System. 【Results and Recommendations】 1. Preliminary findings from analysis of the questionnaire interview showed that users became less satisfied with the new version communication means the longer they were in use of computers. Users who knew more about the use of the reporting system were more satisfied with the new communication means, were at the same time, more satisfied with the communication effects of the improved version. These facts suggested that the new reporting system was less user-friendly in the designing of interface and procedures. The system required more work, more detailed inputs, and thus added additional burdens on the part of the users. The more the users understood the reporting system, their satisfaction was higher, indicating that, for the new version reporting system to function in full, training of the users in the use of the system should be strengthened. 2. From the descriptive analysis, it was found that the average score of user satisfaction on the “information change reporting procedures” was as high as 2.8095, suggesting that the users were fairly satisfied. The satisfaction score on “reporting procedures” was the lowest at 2.3934. The overall satisfaction score on the use of the new version as a communication means was 2.558. 3. Findings from the open-end questions gave the following recommendations: taking too much time, too slow, frequency of the web too narrow, unstable, and unable to load, too detailed, issues related to operational procedures, issues related to information management and additional functions, etc. 4. By analysis of the in-depth interview, some issues were raised and recommendations made to the central and the local competent authorities. 5. Through questionnaire survey and in-depth interview, some recommendations concerning policies, organizational communication, management and practical operation were made. 【Key Words】 Communicable Disease Reporting System, SARS (Severe Acute Respiratory Syndrome), organizational communication, communication channels, Center for Disease Control, the Department of Health

Die Fusionsreaktion des Coronavirus MHV wird vom S-Protein vermittelt. In der vorliegenden Arbeit wurde der Eintrittsweg von MHV-A59 in Mauszellen untersucht. Die Infektivität kann durch lysosomotrope Substanzen und Inhibitoren der Clathrin-abhängigen Endozytose gehemmt werden. Der Eintritt von MHV-A59 in Mauszellen erfolgt über die Clathrin-abhängige Endozytose und setzt die anschließende Fusion der viralen und zellulären Membran bei niedrigem pH-Wert voraus. Fluoreszenzmikroskopische Studien zur Interaktion fluoreszenzmarkierter MHV-A59 Partikel mit Mauszellen bestätigen, dass MHV-A59 über Endozytose aufgenommen wird. Nach Bindung der Viren an die Zellen und anschließende Erniedrigung des pH-Wertes kommt es zur Färbung der Plasmamembran. Die Erniedrigung des pH-Wertes in Abwesenheit des Rezeptors führt zu einer irreversiblen Konformationsumwandlung im viralen Fusionsprotein, die die Inaktivierung der Fusionsaktivität und den Verlust der Infektivität zur Folge hat. Die Ergebnisse deuten auf die Beteiligung des endozytotischen Weges für den viralen Eintritt von MHV-A59 hin. Ein niedriger pH-Wert eines zellulären endosomalen Kompartiments induziert vermutlich die Konformationsänderung im S-Protein und löst die Fusionsreaktion aus. Ein vorläufiges 3D-Modell des S-Proteins von MHV-A59 konnte erstellt werden. Darüber hinaus wurde die Struktur und Fusionsfähigkeit des S-Proteins von SARS-CoV analysiert. Ein Zell-Zell-Fusionsassay konnte nachweisen, dass die Fusion zwischen S-Protein und ACE2-exprimierenden Zellen sowohl abhängig vom pH-Wert als auch von der proteolytischen Spaltung in S1- und S2-Untereinheit ist und durch Erniedrigung des pH-Wertes zusätzlich verstärkt werden kann. Im abschließenden Teil der Arbeit wurde auf Basis theoretischer Untersuchungen eine Vorhersage des mutmaßlichen Fusionspeptids des S-Proteins von MHV-A59, welches alle wesentlichen Merkmale eines internen Fusionspeptids aufweist, vorgenommen. Es liegt nahe der "Heptad-Repeat" (HR) Domäne HR1. / Fusion of the Coronavirus MHV-A59 is mediated by the viral S-protein. The entry pathway of MHV-A59 into murine cells was studied in this work. Infection was strongly inhibited by lysosomotropic compounds and substances interfering with clathrin-dependent endocytosis, suggesting that MHV-A59 is taken up via endocytosis and delivered to acidic compartments. Fluorescence microscopy of labeled MHV-A59 confirmed that the virus is taken up via endocytosis. When the virus was bound to cells and the pH was lowered to 5.0, we observed a strong labeling of the plasma membrane. Electron microscopy revealed low pH triggered conformational alterations of the S-ectodomain. These alterations are likely to be irreversible because low pH-treatment of viruses caused an irreversible loss of fusion activity. The results imply that endocytosis plays a major role in MHV-A59 infection and that the acidic pH of the endosomal compartment triggers a conformational change of the S-protein mediating fusion. Furthermore the conformation of the trimeric spike protein of the murine hepatitis virus A59 was characterized by cryoelectron microscopy. A preliminary 3D-reconsruction of the native structure could be accomplished. Besides we studied the structure and fusion capability of the spike protein expressed by SARS-CoV. The cell-based fusion assay revealed that fusion of spike protein and ACE2-receptor expressing cells was strongly dependent on low pH and on proteolytic cleavage of the S-protein into S1 and S2 subunit. Additionally fusion could be significantly increased by lowering of the pH. The theoretical part of the thesis allowed the identification of the putative fusion peptide, which showed main characteristics of internal fusion peptides. It allows the heptad regions of the spike protein to assemble in the six-helix bundle structure (6HB). This structure is of great importance to initiate the approximation of viral and cellular membrane and thus to induce fusion.

Globalt har hela världens befolkning påverkats både ekonomiskt och psykiskt av coronaviruset SARS-CoV-2, som har drabbat så många människor med covid-19 att det klassas som en pandemi. Strax efter pandemins utbrott upptäcktes det att viruset utsöndras från avföring och ut i spillvattennätet som leder till reningsverken. Då virusmängden ökar i avloppsvattnet ökar även covid-19 fallen i samhället. Ökning av virusmängd i avloppsvatten kan nämligen signalera om att det förekommer smittspridning i samhället. Avloppsvattenbaserad övervakning kan dock användas som komplement till andra teststrategier vilket EU-kommissionen har nämnt i en rekommendation. Trender kan analyseras för att i ett tidigt skede informera sjukvård och regioner om ökad smittspridning.  På Kungsängens reningsverk i Västerås kommun har Mälarenergi analyserat avloppsvattnet för att ta reda på om ökning av virus i avloppsvatten kan indikera på ökad smittspridning i Västerås kommun. De har samlat in proverna och skickat det till SGS Analytics AB Sweden som har analyserat proverna med RT-qPCR. CT-värdena har normaliserats med vattenflöden. Korrelationstest har gjorts mellan virusmängd i avloppsvattnet och covid-19 fall, dödsfall samt IVA-fall. Det fanns ett signifikant svagt negativt samband mellan virusmängd i avloppsvatten och covid-19 fall per vecka. Mellan virusmängd och IVA-fall eller dödsfall fanns inget samband. Det finns en del felkällor som kan ha påverkat virusmängden. Vid höga vattenflöden kan PCR inhibitorer från tillskottsvatten och lakvatten ha påverkat CT-värdena. Värdena är höga på sommaren trots att covid-19 fall, dödsfall och IVA-fall var som lägst. Inhibitorer skapar direkt eller indirekt högre CT-värden vilket tolkas som lägre virusmängder.

Many scientific disciplines rely on the construction and use of models: biomedical sciences are no exception. This PhD thesis addresses several aspects of the practice of scientific modeling. First, I discuss the nature of modeling as such, proposing a novel, complementary account of scientific modeling which I term the experimentation-driven modeling account and which drives the construction of mechanistic models in many fields of biological and biomedical research, such as cancer immunology. Second, I scrutinize an objection to the mechanistic account of explanation according to which the account fails to accommodate the common practice of idealizing difference-making factors. I argue that this objection ultimately fails because it is riddled with a number of conceptual inconsistencies. Third, I analyze the roles of similarity judgments in some fields of cancer research which employ a variety of mouse models to learn about the disease mechanisms, arguing that by appreciating the epistemic complexities it is possible to shed new light on more general philosophical debates regarding scientific representation. Fourth, mechanisms can also be studied using more theoretical apparatus in the form of simulations. I investigate an example of an agent-based model used to model the outbreak of SARS-CoV-2...

Bakgrund: I slutet av 2019 upptäcktes flertalet fall av pneumoni av okänd etiologi i Wuhan, Kina. Efter isolering och sekvensering framkom det att det rörde sig om ett coronavirus, benämnt SARS-CoV-2. Sociala restriktioner och munskydd har inte lyckats stoppa denna pandemi, och hoppet ligger nu på de olika vaccinkandidater som började utvecklas under 2020. Syfte: Syftet var att jämföra olika vaccins effektivitet och förekomst av olika biverkningar. Metod: En systemisk litteraturstudie utfördes, där en sökning i Pubmed utfördes och fyra artiklar valdes ut till arbetet för att jämföra vaccineffektivitet och biverkningar för de tre vaccin som var godkända av läkemedelsverket i februari. Resultat: Pfizer/BioNTechs mRNA-vaccin hade en effektivitet på 94,8%, Modernas mRNA-vaccin en effektivitet på 94,1% och Oxford-AstraZenecas vektorvaccin uppvisade en effektivitet på 70,4%. De vanligaste biverkningarna vid vaccinering var smärta vid injektionsplatsen, huvudvärk samt utmattning. Slutsats: En tillfredsställande jämförelse kunde inte genomföras då de olika fas III studierna utfördes på olika åldersgrupper och i olika delar av världen där SARS-CoV-2 mutationerna skiljde sig åt, vilket kan ha påverkat resultaten. / Background: At the end of 2019, several cases of pneumonia of unknown ethology were discovered in Wuhan, China. After isolating and sequencing the pathogen it became apparent that it was a Coronavirus, named SARS-CoV-2. Social restrictions and mask wearing mandates have not managed to stop this pandemic, and the hope lies with the different vaccine candidates that started to be developed during 2020. Aim: The aim was to compare different vaccines efficacy and prevalence of side effects. Method: A systemic literature study was implemented, the search was done in Pubmed and four papers were selected to compare vaccine efficacy and side effects for the three vaccines that were approved by Läkemedelsverket in February. Results: Pfizer/BioNTech’s mRNA-vaccine showed an efficacy of 94,8%, Moderna’s an efficacy of 94,1% and Oxford-AstraZeneca’s vector vaccine showed an efficacy of 70,4%. The most common side effects following vaccination was pain at the site of injection, headache and fatigue. Conclusion: A satisfying comparison could not be achieved since the different phase III studies were performed on different age groups and in different parts of the world where SARS-CoV-2 mutations differ, which could impact the results.

The virus SARS-CoV-2 gave rise to a global pandemic and several vaccines, whose efficiency needed to be evaluated, have been developed. Our immune system is regulated by several mechanisms that activate and inhibit immune response. PD-1 and its ligand PD-L1 are immune inhibitors with a possible correlation between the potency of the immune response and the number of inhibitors. The hypothesis of this study is that individuals with a lower antibody response after vaccination have higher levels of PD-1/PD-L1. Using an ELISA, the concentration of the proteins was measured from blood plasma from 19 individuals from the CoVacc Cohort, with known antibody response after one as well as two doses of vaccine. The study found a significant correlation between the inhibitors PD-1 and PD-L1 after both the first and the second dose. No correlation was found between the response of antibodies and PD-1/PD-L1 and the hypothesis is therefore rejected. It is possible that the interval between each dose of vaccine and the collection of blood plasma was not optimized for this study. It is also possible that the number of individuals that were included in this study was too low. Considering this result, more research should be conducted on the subject before an absolute conclusion can be drawn. / Viruset SARS-Cov-2 gav upphov till en global pandemi och flera vacciner vars effektbehövde utvärderas har utvecklats. Vårt immunförsvar regleras av flera mekanismersom samverkar genom att aktivera respektive hämma immunförsvaret. PD-1 och dessligand PD-L1 är immuninhibitorer med en möjlig korrelation mellan styrkan hosimmunsvaret och mängden inhibitorer. Hypotesen för denna studie är att individermed ett lägre antikroppssvar efter vaccination har högre nivåer av PD-1 och PD-L1.Med hjälp av en ELISA mättes koncentrationen av PD-1 och PD-L1 med blodplasmafrån 19 individer ur CoVacc kohorten med kända antikroppsnivåer som fått enrespektive två doser av vaccin mot COVID-19. Studien fann en signifikant korrelationmellan hämmarna PD-1 och PD-L1 både efter första och andra dosen. Ingenkorrelation hittades mellan antikroppsresponsen och nivåerna av PD-1 och PD-L1 ochhypotesen förkastas därför. Det är möjligt att tidpunkten för provtagning eftervaccindoserna inte valdes optimalt för denna undersökning. Det är också möjligt attför få individer ingick i studien. Mot bakgrund av detta bör mer forskning göras i ämnetinnan en absolut slutsats kan dras.