Experiments were conducted to investigate the effects of formulating rations using different ingredients and of manipulating the cation-anion balance of the rations on production, acid-base status, metabolism of macrominerals and renal function of dairy cows. The effects of dietary cation-anion balance were studied during early, mid and late lactation as well as during the dry period. Feeding an alfalfa-haylage based diet vs a corn silage based diet, both having the same cation-anion balance did not affect the voluntary consumption, milk yield or milk composition of cows in early lactation. The acid-base status of the animals was not affected by dietary treatment. The lower urinary bicarbonate concentration observed with the alfalfa haylage-based diet was not associated with a lower total urinary bicarbonate excretion since urine volume was significantly higher than when cows were fed the corn silage-based diet. Manipulating dietary cation-anion balance, however, resulted in changes in acid-base status at all stages of lactation studied. Urinary bicarbonate concentration and total daily excretion were increased by a higher dietary cation-anion balance at all stages of lactation. Similar effects of dietary cation-anion balance on urinary bicarbonate did not, however, translate into similar changes in production or intake by cows at differing stages of lactation. Cows in early and mid lactation seemed to have benefited more from a highly positive dietary cation-anion balance than cows in late lactation or dry period.

Focusing on the 1851 International Sanitary Conference, this dissertation analyses an important episode in the international regulation of health, trade, passengers, and cargo in a period of epidemic crisis. It argues that a group of diplomats and physicians appointed to represent 12 European nations instituted a new international forum that extended – and occasionally rivalled – national and local agencies for epidemic governance. Together, delegates endeavoured to establish a common sanitary policy in Europe and in the Orient. By creating shared surveillance and judicial mechanisms – while standardising definitions and practices – delegates aimed to engineer the flow of people, vessels, cargo, and diseases in the Mediterranean region. As a transnational forum, the Conference was a platform where doctors and diplomats reinterpreted models of public health and sanitary administration while creating institutions that challenged conventional concepts of borders, national policy, and state sovereignty. As a multinational event, the Conference marked the unprecedented transition from local, national and, bilateral public health policies into a coherent transnational project for the governance of epidemics. The dissertation is based on extensive research conducted in hitherto largely unexplored medical, diplomatic, and national collections in Britain, France, Italy, Portugal, Spain, and the United States of America. Sources ranging from diplomatic correspondence to medical publications and personal diaries, tie together multiple national and professional perspectives while untangling a diversity of personal and state agendas that fundamentally shaped the foundation of international public health mechanisms and contributed towards the crystallisation of medical concepts. Chapter one demonstrates how economic and political concerns about the impact of quarantine on international trade led to calls for international regulation and the standardization of quarantine practices in the Mediterranean region. Drawing on medical reports, pamphlets and diplomatic correspondence, the chapter exposes the multitude of quarantine practices in the Mediterranean region and a growing international demand for prophylactic reform. These exchanges, it is shown, culminated with the organization of the 1851 International Sanitary Conference in Paris. Chapter two argues that the Conference challenged previous diplomatic and medical protocols by including two professional groups in the process of regulating international public health. The lack of precedent allowed diplomatic and medical delegates to establish new rules for the conduct of the conference, which gave them a relatively high level of autonomy from the states they represented. Chapter three focuses on the problems of constructing a shared aetiological classification and regulating quarantine practices. It shows that, although doctors gained progressive control over the Conference, ultimately diplomatic agendas shaped the final outcome. In addition, it demonstrates that, rather than defending the elimination of quarantines, liberal states supported the continuation of quarantine practice in the Mediterranean; albeit that they managed to severely limit its operation in practice. Finally, chapter four examines how European and Oriental sanitary institutions were uniformly redesigned and new international judicial mechanisms created. These measures variously affected the sovereignty of the participating states by limiting their independent capacity to set national epidemic policies. However, the chapter argues that these negotiations took the shape of sovereignty bargains: by loosening control over specific elements of their sovereignty, states managed to advance their political, economic and sanitary agendas. By looking at the International Sanitary Conference of 1851, this dissertation shows how the foundations of international public health had consequences not only for the control of epidemic diseases and the circulation of goods and people in the Mediterranean region, but also for the authority and status of the nation states. By doing so, it reveals that international public health governance resulted from the amalgamation of a particular configuration of expert and diplomatic struggles and compromises. Moreover, the dissertation shifts the traditional local and national focus in the history of medicine to a wider and international context where local and national traditions struggled to produce coherent discourses and practices.

Background: Dengue is a viral infectious disease that is transmitted by mosquitoes. The disease causes a significant health burden in tropical countries, and has been a public health burden in Singapore for several decades. Severe complications such as hemorrhage can develop and lead to fatal outcomes. Before tetravalent vaccine and drugs are available, vector control is the key component to control dengue transmission. Vector control activities need to be guided by surveillance of outbreak and implement timely action to suppress dengue transmission and limit the risk of further spread. This study aims to explore the feasibility of developing a dengue early warning system using temperature and rainfall as main predictors. The objectives were to 1) analyze the relationship between dengue cases and weather predictors, 2) identify the optimal lead time required for a dengue early warning, 3) develop forecasting models, and 4) translate forecasts to dengue risk indices. Methods: Poisson multivariate regression models were established to analyze relative risks of dengue corresponding to each unit change of weekly mean temperature and cumulative rainfall at lag of 1-20 weeks. Duration of vector control for localized outbreaks was analyzed to identify the time required by local authority to respond to an early warning. Then, dengue forecasting models were developed using Poisson multivariate regression. Autoregression, trend, and seasonality were considered in the models to account for risk factors other than temperature and rainfall. Model selection and validation were performed using various statistical methods. Forecast precision was analyzed using cross-validation, Receiver Operating Characteristics curve, and root mean square errors. Finally, forecasts were translated into stratified dengue risk indices in time series formats. Results: Findings showed weekly mean temperature and cumulative rainfall preceded higher relative risk of dengue by 9-16 weeks and that a forecast with at least 3 months would provide sufficient time for mitigation in Singapore. Results showed possibility of predicting dengue cases 1-16 weeks using temperature and rainfall; whereas, consideration of autoregression and trend further enhance forecast precision. Sensitivity analysis showed the forecasting models could detect outbreak and non-outbreak at above 90% with less than 20% false positive. Forecasts were translated into stratified dengue risk indices using color codes and indices ranging from 1-10 in calendar or time sequence formats. Simplified risk indices interpreted forecast according to annual alert and outbreak thresholds; thus, provided uniform interpretation. Significance: A prediction model was developed that forecasted a prognosis of dengue up to 16 weeks in advance with sufficient accuracy. Such a prognosis can be used as an early warning to enhance evidence-based decision making and effective use of public health resources as well as improved effectiveness of dengue surveillance and control. Simple and clear dengue risk indices improve communications to stakeholders.

Introduction: Recent Ebola epidemic in West Africa have put viral hemorrhagic fever diseases in the spotlight. Uganda has had several outbreaks throughout the years, which have successfully been managed. Nurses’ patient education plays an important role in the work to increase public awareness about viral hemorrhagic fever diseases. Objectives: To assess how nurses at the emergency department educate the patients and relatives about the viral hemorrhagic fever diseases. Methods: An explorative and descriptive qualitative study with qualitative approach have been used. In-depth interviews with 18 open-ended questions have been conducted with nurses in the emergency department. Data was analyzed by qualitative content analysis and analyzed with Peplau’s theory of interpersonal relationship. Results: Through data analysis four categories were developed; Wide variety of educational techniques, Experienced obstacles, How to attain wider audience and Preferable characteristics as an educating nurse. Nurses used many different approaches when educating about viral hemorrhagic fever diseases, often uniquely combined. Lack of time and too unstable patients in the emergency department were seen as the main obstacles to educate. Methods to reach the community and employing a special education-nurse on the ward were suggestions to improve the preventive work against viral hemorrhagic fever diseases. Conclusion: Nurses are aware of the importance of patient education and use the educational methods they believe to be the most effective. However, patients in the emergency department often come in too late and priority should be on preventive measures. Training the nurses in educational techniques and patient education could be a key in decreasing the risk of coming outbreaks. / Bakgrund: Den senaste ebolaepidemin i västafrika har gjort att blödarsjukdomar hamnat i rampljuset. Uganda har genom åren drabbats av flera utbrott som framgångrikt hanterats. Sjuksköterskors patientutbildning spelar en viktig roll i arbetet för att öka allmänhetens medvetenhet om blödarsjudkomar. Syfte: Att undersöka hur sjuksköterskor på akutmottagningen utbildar patienter och anhöriga om blödarsjukdomar. Metod: En explorativoch deskriptiv kvalitativ studie med kvalitativ ansats användes. Sjuksköterskor som arbetar på akutmottagningen har djupintervjuats med 18 öppna frågor. Data har analyserats med en kvalitativ innehållsanalys och analyserats utifrån Peplaus ”interpersonal relationship theory”. Resultat: Genom dataanalysen utvecklades fyra kategorier; Stor variation på utbildningstekniker, Upplevda hinder, Hur man ska nå en bredare publik och Önskvärda egenskaper som utbildande sjuksköterska. Sjuksköterskorna använder många olika metoder för utbilda patienter och anhöriga om blödarsjukdomar, ofta i unika kombinationer. Tidsbrist och alltför instabila patienter på akutmottagningen sågs som de största hindren för att utbilda. Metoder för att nå allmänheten och att anställa en speciell utbildningssjuksköterska på avdelningen var några av förslagen för att förbättra det förebyggande arbetet mot blödarsjukdomar. Slutsats: Sjuksköterskorna är medvetna om vikten av patientutbildning och använder de pedagogiska metoder de anser vara mest effektiva. Då patienterna kommer till akutmottagningen är det dock ofta för sent och preventiva åtgärder borde prioriteras. Att öka sjuksköterskornas kunskap i utbildningstekniker och patientutbildning kan vara en viktig del i det preventiva arbetet för att minska risken för kommande utbrott.

Immune cytokines tumor necrosis factor alpha and type I interferons provide front-line defense against viral infection and are regulated in part by ubiquitin (Ub) and Ub-like molecules. Ubiquitin and Ub-like molecule ISG15 share a conserved C-terminal motif where a terminal glycine residue becomes attached to cellular target proteins. Nairoviruses and arteriviruses contain an ovarian tumor domain-containing protease (OTU protease) that was found to corrupt pathways by removing Ub or ISG15 from target proteins. This broad substrate specificity is unlike mammalian deubiquitinating enzymes, which cannot recognize both substrates. To understand how viral OTU domain-containing proteases remove Ub and ISG15, the crystal structure of the Crimean-Congo Heamorhaggic Fever nairovirus (CCHFV) was determined with Ub to 2.5 Å resolution. A computational model was built of the CCHFV Otu protease bound to ISG15 as well. The CCHFV Otu protease has several structural differences from known OTU proteases, manifesting in its broad substrate recognition capability.

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Impulsive differential equations are useful for modelling certain biological events. We present three biological applications showing the use of impulsive differential equations in real-world problems. We also look at the effects of stability on a reduced two-dimensional impulsive HIV system. The first application is a system describing HIV induction-maintenance therapy, which shows how the solution to an impulsive system is used in order to find biological results (adherence, etc). A second application is an HIV system describing the interaction between T-cells, virus and drugs. Stability of the system is determined for a fixed drug level in three specific regions: low, intermediate and high drug levels. Numerical simulations show the effects of varying drug levels on the stability of a system by including an impulse. We reduce these two models to a two-dimensional impulsive model. We show analytically the existence and uniqueness of T-periodic solutions, and show how stability changes when varying the immune response rate, the impulses and a certain nonlinear infection term. The third application shows how seasonal changes can be incorporated into an impulsive differential system of Rift Valley Fever, and looks at how stability may differ when impulses are included. The analysis of impulsive differential systems is crucial in developing more realistic mathematical models for infectious diseases.

Immune cytokines tumor necrosis factor alpha and type I interferons provide front-line defense against viral infection and are regulated in part by ubiquitin (Ub) and Ub-like molecules. Ubiquitin and Ub-like molecule ISG15 share a conserved C-terminal motif where a terminal glycine residue becomes attached to cellular target proteins. Nairoviruses and arteriviruses contain an ovarian tumor domain-containing protease (OTU protease) that was found to corrupt pathways by removing Ub or ISG15 from target proteins. This broad substrate specificity is unlike mammalian deubiquitinating enzymes, which cannot recognize both substrates. To understand how viral OTU domain-containing proteases remove Ub and ISG15, the crystal structure of the Crimean-Congo Heamorhaggic Fever nairovirus (CCHFV) was determined with Ub to 2.5 Å resolution. A computational model was built of the CCHFV Otu protease bound to ISG15 as well. The CCHFV Otu protease has several structural differences from known OTU proteases, manifesting in its broad substrate recognition capability.

Theileria parva is a complex protozoan parasite causing East Coast fever in Eastern and Central Africa. Vaccination using live parasites is an effective control measure and has been used in Zambia based on locally isolated and introduced T. parva stocks. Diversity among T. parva populations was investigated in parasites from two Zambian provinces with different disease epidemiologies and control histories. Isolates from the pre-vaccination era, local and exotic stocks used for vaccination, and one recent field isolate were cloned and passaged in vitro to study genomic stability over time. The results of the data from three genome-wide probes indicate a marked homogeneity and stability among the Zambian isolates in contrast to East African isolates. Results from Southern blot profiles and the polymorphic immunodominant molecule (PIM) sequence analysis suggest a common origin for the Zambian isolates from the pre-vaccination era, except for one isolate (Zam5) from Southern Province. This isolate showed characteristics suggesting a buffalo origin. Assays for genotype characterisation were developed using five allelic markers. Multilocus characterisation revealed identical profiles in a recent Zambian isolate from Southern Province and two components of an exotic cocktail vaccine, indicating the escape of one of the vaccine stocks in the field. Characterisation of T. parva field populations by RFLP-PCR assays after immunisation revealed the presence of dominant genotypes from those that had been used for vaccination. Circumstantial evidence for the involvement of one of the exotic vaccine parasites in epidemics in Southern Province is presented and a hypothesis formulated for the rapid spread of this genotype. Analysis of the characterisation data suggested the existence of two groups of T. parva parasites of different origin. The classic T. parva group, characterised by a dimorphism of the p150, p104 and p32 loci and the absence of a p67 insert and a buffalo-derived group which showed a polymorphism of p150, p104 and p32 and the presence of a p67 insert. There is evidence that recombination occurs, resulting in parasites that have characteristics of both groups. The relevance of these recombinant parasites in the epidemiology of the disease seems low. Characterisation of larger samples from areas of regular buffalo-cattle contact is necessary to clarify this. Sequence analysis of the most discriminative locus (PIM) was undertaken and gene conversion could be the main mechanism generating diversity. A more appropriate nomenclature for T. parva is proposed based on the growing evidence of molecular differences among isolates and stocks.

Zusammenfassung Katja Schwartau Peripartale hämatologische und klinisch-chemische Blutuntersuchungen zur Frühdiagnostik der Dislocatio abomasi, Gebärparese, Retentio secundinarum und Mastitis bei Milchkühen Medizinische Tierklinik der Veterinärmedizinischen Fakultät der Universität Leipzig Eingereicht im Mai 2011 Bibliographische Angaben 94 Seiten, 22 Abbildungen, 19 Tabellen, 210 Literaturangaben, Schlüsselwörter: Labmagenverlagerung, Gebärparese, Retentio secundinarum, Mastitis, Kuh Produktionskrankheiten haben in den letzten Jahren immer mehr an Bedeutung gewonnen. Diese leistungsassoziierten Bestandserkrankungen tragen wesentlich zur kurzen Nutzungsdauer von ca. 2,5 Jahren der Milchkühe bei. Es ist deshalb besonders wichtig, ihre Prophylaxe einschließlich der Früherkennung in den Vordergrund zu stellen. In der vorliegenden Untersuchung wurden deshalb frühdiagnostische Möglichkeiten der LMV (Labmagenverlagerung), GP (Gebärparese), Retentio sec. (Retentio secundinarum) und Mastitis geprüft. Des Weiteren wurden die Kühe in einer Gruppe „krank“ und einer Gruppe „gesund“ gegenübergestellt, um durch Stoffwechselabweichungen generell subklinische Veränderungen zu erkennen, die Hinweise auf bevorstehende Erkrankungen geben. Besondere Beachtung fand für die Bewertung des Erkrankungsrisikos die odds ratio. In die Untersuchung wurden insgesamt 398 Schwarzbunte Kühe einbezogen. 49 Tiere waren an einer LMV, 121 Tiere an einer GP, 131 an einer Retentio sec. und 119 Tiere an einer Mastitis erkrankt. Im Gruppenvergleich gesund/krank wurden 347 erkrankte Kühe mit 51 klinisch gesunden Tieren verglichen. Es wurden bei allen Kühen 14-7 d a.p. (Tage ante partum) und 3 d p.p. (Tage post partum) Blutproben entnommen. Es wurden Parameter des Energie-, Fett- und Leberstoffwechsels (FFS [Freie Fettsäuren], BHB [ß-0H-Butyrat], Cholesterol, Glucose, Insulin, AST [Aspartat-Amino-Transferase], Bilirubin), des Eiweißstoffwechsels (Albumin, Haptoglobin, TP [Gesamt-Eiweiß], Harnstoff, Kreatinin) und der Leukozyten sowie des Mineralstoffwechsels (Na [Natrium], K [Kalium], Cl [Chlorid], Ca [Calcium], Pi [anorganisches Phosphat], AP [Alkalische Phosphatase]) und der CK [Creatinkinase] bestimmt und mit gesunden Kühen verglichen. 92 Auf das Risiko einer LMV weisen a.p. besonders Konzentrationssteigerungen des Haptoglobins hin. Aber auch die Mediane der Glucose und der AP liegen außerhalb des Referenzbereichs bei Tieren, die später an einer LMV erkranken. Drei d p.p. kommen signifikante Konzentrationsanstiege der FFS, des BHB und des Bilirubin sowie signifikante Konzentrationsabnahmen des Insulin (odds ratio 8,43) bis unter den Normbereich hinzu. Die Aktivitäten der AP und auch die Konzentrationen von Cholesterol und Ca bleiben ebenfalls unter dem Normbereich. Die Mediane der AST-Aktivität und der Haptoglobinkonzentration liegen oberhalb des Referenzbereichs. Auf das Risiko einer GP weisen a.p. und p.p die verminderte AP-Aktivität sowie Konzentrationsanstiege der FFS (odds ratio 1,78) hin. Drei d p.p ergänzen die Konzentrationen des BHB, des Bilirubins und des Haptoglobins (odds ratio 4,59) oberhalb der Referenzbereiche die Veränderungen. Der Median der Insulinkonzentration liegt 3 d p.p. unter dem Referenzbereich. Einer Retentio sec. gehen erhöhte Glucosekonzentrationen a.p. voraus. Der Median der AP-Aktivitäten liegt schon a.p. unter dem Normbereich. Drei d p.p. unterscheidet er sich signifikant von Kühen ohne Retentio sec. Hinweise auf Mastitiden liefern p.p. die Konzentrationen des BHB (odds ratio 1,78). Die Mediane der Glucosekonzentrationen liegen a.p. oberhalb und die der AP-Aktivitäten unterhalb der Referenzbereiche. Drei d p.p. kommen Steigerungen der Haptoglobin-, Glucose- und Bilirubinkonzentrationen sowie Aktivitätssteigerungen der AST bis über den Normbereich hinzu. Als Besonderheit liegen die Ca- und Pi-Konzentrationen aufgrund des geringeren Abflusses bei einer verminderten Milchleistung signifikant über denen der gesunden Kühe. Für die Entstehung postpartaler Erkrankungen generell verdienen die signifikanten Konzentrationssteigerungen der Glucose sowie die Abnahme der AP-Aktivität besondere Beachtung. Das BHB (odds ratio 1,92 a.p.) und die CK (odds ratio 2,17 a.p.) weisen auf ein erhöhtes Krankheitsrisiko hin. Drei d p.p. kommen zu den Veränderungen dieser Parameter noch signifikante Konzentrations- bzw. Aktivitätssteigerungen der FFS, des BHB, der CK, des Bilirubins, der AST und des Haptoglobins (odds ratio 4,61) sowie erniedrigte Ca-Konzentrationen hinzu. Die Untersuchungen haben gezeigt, dass a.p. generell Abweichungen des Energiestoffwechsels und im Besonderen gesteigerte Glucosekonzentrationen sowie erniedrigte AP-Aktivitäten ein erhöhtes Risiko für postpartale Erkrankungen anzeigen. Höhere Aussagekraft besitzen Kontrollen am 3. d p.p. mit den Parametern Insulin (odds ratio 8,4), FFS, BHB und Haptoglobin (odds ratio 4,61), deren Konzentrationen gegenüber gesunden Kühen signifikant abweichen. Ähnlich gute Eignung zeigen, Bilirubin, AST und Ca.