Chaque année, les maladies respiratoires figurent parmi les dix premières causes de décès dans le monde. L'exposition continue de l'épithélium pulmonaire aux particules et microorganismes aériens explique en partie cette vulnérabilité. Cette situation génère un dilemme immunologique pour l'organisme : il doit produire une réponse immunitaire adéquate pour protéger l’épithélium respiratoire tout en limitant l’inflammation qui pourrait nuire à son intégrité. Les lymphocytes T-CD8+ jouent un rôle essentiel dans l’immunosurveillance des cellules infectées ou tumorales. Leur activation rapide repose sur l’expression généralisée du Complexe Majeur d’Histocompatibilité de type I (CMH I) par toutes les cellules nucléées. Notre laboratoire a découvert en 2020 que les Cellules Épithéliales Pulmonaires (CEP) expriment peu de CMH I. Cette observation soulève des questions sur l'efficacité de la surveillance immunitaire dans les poumons, souvent cibles de maladies graves comme les infections, les cancers et les maladies chroniques. Cette thèse vise à explorer les mécanismes régulant l'expression du CMH I dans les CEP, en conditions normales et pathologiques, afin de comprendre les implications des variations de son expression sur la santé respiratoire. La première étude présentée dans cette thèse aborde la régulation du CMH I dans les CEP de souris en réponse à un contexte inflammatoire. Ces travaux ont révélé la capacité des CEP à augmenter significativement leur expression de CMH I en cas d'inflammation. À l'aide de modèles de souris transgéniques, les molécules impliquées dans cette régulation ont été identifiées, en particulier les Interférons (IFN) via les facteurs STAT1, STAT2 et NLRC5. De plus, ces analyses ont mis en évidence une association entre l'augmentation du CMH I et une diminution significative de gènes essentiels à l'intégrité de l'épithélium pulmonaire, soulignant ainsi un équilibre délicat entre défense immunitaire et maintien de l'intégrité tissulaire. Une seconde étude, basée sur des analyses de séquençage ARN de cellules uniques, a confirmé la faible expression du CMH I dans les CEP humaines. Ces résultats ont mis en lumière une augmentation significative de son expression chez des patients atteints de trois types de maladies respiratoires chroniques : la Maladie Pulmonaire Obstructive Chronique (MPOC), la Fibrose Pulmonaire Idiopathique (FPI) et la Fibrose Kystique (FK), principalement médiée par la voie NF-B. De plus, cette étude a révélé un dimorphisme sexuel dans l’expression du CMH I chez des donneurs sains ainsi que chez les patients atteints de MPOC et de FPI, avec des tendances opposées dans les deux maladies. Les analyses d’expression différentielle de gènes suggèrent une implication du stress oxydatif dans la régulation différenciée du CMH I entre hommes et femmes. Ces travaux représentent une avancée significative dans la compréhension des mécanismes régulant le CMH I dans les CEP, ainsi que des facteurs influençant la diversité de son expression. Les variations d’expression du CMH I dans les CEP pourraient jouer un rôle majeur dans la pathogenèse des maladies respiratoires et dans la susceptibilité individuelle à différentes affections. Ces découvertes ouvrent la voie à une meilleure compréhension de la physiologie pulmonaire, des maladies respiratoires, et à des approches thérapeutiques plus ciblées et personnalisées. / Respiratory diseases consistently rank among the top ten causes of global mortality every year. The continuous exposure of the pulmonary epithelium to airborne particles and microorganisms partly explains this vulnerability. This situation creates an immunological dilemma for the organism: it must produce an adequate immune response to protect the respiratory epithelium while limiting inflammation that threatens its integrity. CD8+ T lymphocytes play an essential role in immunosurveillance against infected or tumor cells. Their swift activation hinges on the widespread expression of the major histocompatibility complex class I across all nucleated cells. Our laboratory discovered in 2020 that Lung Epithelial Cells (LECs) exhibit shallow levels of MHC I expression. This discovery prompted critical inquiries into the efficacy of pulmonary immune surveillance, crucial given the lungs' heightened susceptibility to various ailments such as infections, cancers, and chronic illnesses. This thesis aims to explore the mechanisms regulating MHC I expression in LECs under normal and pathological conditions to understand the implications of its expression variations on respiratory health. The first study that will be presented examines MHC I regulation in mice's LECs during inflammation. These works highlighted the ability of LECs to significantly increase their expression of MHC I in response to an inflammatory challenge. The molecules involved in this regulation were identified using transgenic mouse models, including IFN through STAT1, STAT2, and NLRC5 factors. Additionally, these analyses revealed an association between increased MHC I expression and a significant decrease in genes essential for the integrity of the pulmonary epithelium, emphasizing a delicate balance between defense and integrity maintenance. In a second study, analyses of single-cell RNA sequencing confirmed the low expression of MHC I in human LECs. These results also demonstrated a significant increase in its expression in LECs from patients with three types of chronic respiratory diseases: Chronic Obstructive Pulmonary Disease (COPD), Idiopathic Pulmonary Fibrosis (IPF), and Cystic Fibrosis (CF), principally mediated by the NF-B pathway. Furthermore, this study highlighted a sexual dimorphism in MHC I expression in healthy donors as well as in patients with COPD and IPF, with opposite directions in the two diseases. Differential gene expression analysis suggests an involvement of oxidative stress in the differentiated regulation of MHC I between men and women. Our comprehensive analyses offer profound insights into the intricate regulatory mechanisms governing MHC I expression in LECs and shed light on the factors contributing to its heterogeneous expression. These variations in MHC I expression levels could significantly influence the pathogenesis of respiratory disorders and individual susceptibilities to diverse respiratory ailments. These works pave the way for a better understanding of pulmonary physiology and respiratory diseases and toward more personalized therapeutic management of chronic respiratory alignments.

He, Qiqiang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 142-154). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

published_or_final_version / abstract / toc / Community Medicine / Master / Master of Philosophy

Diss. (sammanfattning) Stockholm : Karol, inst., 2002. / Härtill 4 uppsatser.

Respiratory diseases are ones of the most common diseases, which are treated by general practitioners. Not only the right diagnosis is essential, but the treatment as well. The treatment of respiratory diseases is usually long-term and often requires repeating. Health treatment of young children in a spa improves their life and health quality, inclusion in a collective of similar aged children, reduces complications of their disease, doses of medicine and highly reduces the risk of development of a chronical disease in adulthood. The aim of this thesis is to chart the use of coordinated rehabilitation in spa Lázně Luhačovice, a. s. and to survey coordinated rehabilitation awareness of spa medical and non medical personnel and children's accompaniment. Three hypotheses were set. Hypothesis 1: Children's accompaniment, who has been to spa health resort repeatedly percieves the care of his child as coordinated unlike the one who has been to spa health resort just once. Hypothesis 2: Medical staff of children spa health resorts percieves the most the medical treatment part of coordinated rehabilitation in contrast with non medical staff. Hypothesis 3: Children's accompaniment is satisfied the most with the medical treatment part of coordinated rehabilitation unlike the pedagogical and social one. A strategy of quantitative research was used, data was gathered by standardized questionnaires in June and July 2015. The standardized questionnaires were given to two different research groups. First one was spa health resort personnel, second one children's accompaniment in the spa Lázně Luhačovice, a. s. Based on statistical calculations the hypotheses can not be rejected, the results are not statistically significant. From the data obtained from the questionnaires, it is noticable that from the spa health resort medical and non medical personnel point of view, there is percieved only the part, which they provide. On the other hand, from the children's accompaniment point of view the rehabilitation is percieved as coordinated in all the parts provided. It is thanks to the fact that the accompaniment, who is in the spa health resort on the expenses of health insurance company, can see all the parts of coordinated rehabilitation as they undergo it together with their children. This thesis contributes to widening awareness of using parts of coordinated rehabilitation in children repeated respiratory diseases treatment, which are provided in facilities of spa Lázně Luhačovice, a.s. and in other health resorts, where there is this kind of care provided as well.

As infecções respiratórias agudas são uma importante causa de morbidade e mortalidade infantil em todo o mundo. Algumas dessas infecções podem resultar em Síndrome Respiratória Aguda Grave (SRAG). Os vírus respiratórios são os principais responsáveis por esta doença. O monitoramento e a vigilância das SRAG e dos vírus respiratórios são importantes para a gestão em saúde minimizando o impacto destas infecções respiratórias. O presente estudo buscou analisar a sazonalidade e impacto clínico das infecções causadas por vírus respiratórios em crianças internadas em hospital pediátrico do Paraná. Foram incluídos no estudo 229 pacientes de 0 até 15 anos de idade, de janeiro de 2012 a dezembro de 2015, com diagnóstico clínico de SRAG e amostra respiratória coletada e enviada ao Laboratório Central do Estado do Paraná para diagnóstico do agente etiológico. A busca dos casos de SRAG foi realizada utilizando o prontuário eletrônico GSUS (Gestão da Assistência de Saúde do SUS), arquivos do setor de fisioterapia e informações do Núcleo de Controle de Infecções hospitalares do hospital do estudo. Dos pacientes incluídos na pesquisa, foi preenchido um formulário de coleta de dados e posteriormente estes foram analisados de acordo com os objetivos da pesquisa. As análises estatísticas foram efetuadas com o pacote estatístico GRAPHPAD PRISM e foi considerado um nível de significância de 5%. A maioria dos pacientes da amostra pertencia à faixa etária de 0 a 6 meses de idade, não houve sexo predominante. No presente estudo as amostras positivas para pelo menos um agente etiológico contabilizaram 76,41%, e o vírus mais prevalente foi o Vírus Sincicial respiratório (VSR). Quanto à sazonalidade da detecção viral, houve predominância no final de outono e início do inverno, mais acentuada para o VSR. Quando analisada as três temperaturas ambientais da região, a incidência de SRAG foi significativamente maior no quartil descendente da temperatura média para mínima. Não foi observada diferença significativa entre os grupos etiológicos pesquisados com relação ao tempo desde o início dos sintomas até a internação. Houve predominância de internamentos em Unidade de Terapia Intensiva. O tempo de internamento foi significativamente maior naqueles pacientes com doença de base e não alterou conforme os agentes etiológicos identificados ou presença de codetecção. Os pacientes que apresentaram padrão misto na radiografia de tórax tiveram um tempo de internamento significativamente maior do que aqueles que apresentaram o padrão infiltrado intersticial. O tempo total foi significativamente menor no grupo Metapneumovírus em relação aos grupos Bordetella pertussis, Influenza, Rinovírus e grupo dos pacientes sem agentes infecciosos detectados. O tempo de ventilação mecânica não apresentou diferenças significativas entre os grupos etiológicos nem com relação à presença ou não de codetecção. A maior parte dos pacientes recebeu alta hospitalar, mas ocorreram três óbitos devido a SRAG, todos em pacientes com alguma doença de base ou condições de risco. / Acute respiratory infections are the most important cause of children morbidity and mortality worldwide. Some of these infections can result in Severe Acute Respiratory Syndrome (SARS). Respiratory viruses are primarily responsible for SARS. The monitoring and surveillance of SARS and respiratory viruses are important for health management, minimizing the impact of these respiratory infections. The present study was about the seasonality and clinical impact of respiratory viruses in children admitted to a pediatric reference hospital. The study included 229 children from 0 to 15 years old, from January 2012 to December 2015, with clinical diagnosis of SARS and respiratory sample collected and sent to the Central Laboratory of the State of Paraná for etiological agent analysis. The search for SARS cases was performed using the GSUS (Health Care Management of SUS) electronic filesystem, records of the center of physiotherapy and information of the Hospital Infection Control Center of the studied hospital. Of the patients included in the research, data collection forms were filled out and later analyzed according to the research objectives. Statistical analyzis were performed with the statistical package GRAPHPAD PRISM and a significance level of 5% was considered. The majority of patients in the sample belonged to the age group 0-6 months of age, and there was no predominant sex. Regarding the risk factors for viral infection, the presence of comorbidity or underlying disease was the most prevalent factor. In the present study, the positive samples for at least one etiological agent accounted for 76.41%, and the most prevalent virus was Respiratory Syncytial Virus (RSV). As for the seasonality of viral detection, there was a predominance in the late fall and early winter, which was more pronounced for RSV. When the environmental temperatures of the region were analyzed, the incidence of SARS was significantly higher in the descending quartile of the average minimum temperature. No significant difference was observed between the studied etiological groups in relation to the time from the beginning of the symptoms until the hospitalization. There was a predominance of hospitalizations in the Intensive Care Unit. The hospitalization time was significantly higher in patients with underlying disease or comorbidities and did not change according to the identified etiological agents or the presence of codetection. Patients who presented a mixed pattern on chest radiography had a significantly longer hospitalization time than those who had the interstitial infiltrate pattern. The total time was significantly lower in the Metapneumovirus group than in the Bordetella pertussis, Influenza, Rhinovirus and group of patients without detected infectious agents. Most patients were discharged from hospital, but there were three deaths due to SARS, all in patients with some underlying disease or risk conditions.

As infecções respiratórias agudas são uma importante causa de morbidade e mortalidade infantil em todo o mundo. Algumas dessas infecções podem resultar em Síndrome Respiratória Aguda Grave (SRAG). Os vírus respiratórios são os principais responsáveis por esta doença. O monitoramento e a vigilância das SRAG e dos vírus respiratórios são importantes para a gestão em saúde minimizando o impacto destas infecções respiratórias. O presente estudo buscou analisar a sazonalidade e impacto clínico das infecções causadas por vírus respiratórios em crianças internadas em hospital pediátrico do Paraná. Foram incluídos no estudo 229 pacientes de 0 até 15 anos de idade, de janeiro de 2012 a dezembro de 2015, com diagnóstico clínico de SRAG e amostra respiratória coletada e enviada ao Laboratório Central do Estado do Paraná para diagnóstico do agente etiológico. A busca dos casos de SRAG foi realizada utilizando o prontuário eletrônico GSUS (Gestão da Assistência de Saúde do SUS), arquivos do setor de fisioterapia e informações do Núcleo de Controle de Infecções hospitalares do hospital do estudo. Dos pacientes incluídos na pesquisa, foi preenchido um formulário de coleta de dados e posteriormente estes foram analisados de acordo com os objetivos da pesquisa. As análises estatísticas foram efetuadas com o pacote estatístico GRAPHPAD PRISM e foi considerado um nível de significância de 5%. A maioria dos pacientes da amostra pertencia à faixa etária de 0 a 6 meses de idade, não houve sexo predominante. No presente estudo as amostras positivas para pelo menos um agente etiológico contabilizaram 76,41%, e o vírus mais prevalente foi o Vírus Sincicial respiratório (VSR). Quanto à sazonalidade da detecção viral, houve predominância no final de outono e início do inverno, mais acentuada para o VSR. Quando analisada as três temperaturas ambientais da região, a incidência de SRAG foi significativamente maior no quartil descendente da temperatura média para mínima. Não foi observada diferença significativa entre os grupos etiológicos pesquisados com relação ao tempo desde o início dos sintomas até a internação. Houve predominância de internamentos em Unidade de Terapia Intensiva. O tempo de internamento foi significativamente maior naqueles pacientes com doença de base e não alterou conforme os agentes etiológicos identificados ou presença de codetecção. Os pacientes que apresentaram padrão misto na radiografia de tórax tiveram um tempo de internamento significativamente maior do que aqueles que apresentaram o padrão infiltrado intersticial. O tempo total foi significativamente menor no grupo Metapneumovírus em relação aos grupos Bordetella pertussis, Influenza, Rinovírus e grupo dos pacientes sem agentes infecciosos detectados. O tempo de ventilação mecânica não apresentou diferenças significativas entre os grupos etiológicos nem com relação à presença ou não de codetecção. A maior parte dos pacientes recebeu alta hospitalar, mas ocorreram três óbitos devido a SRAG, todos em pacientes com alguma doença de base ou condições de risco. / Acute respiratory infections are the most important cause of children morbidity and mortality worldwide. Some of these infections can result in Severe Acute Respiratory Syndrome (SARS). Respiratory viruses are primarily responsible for SARS. The monitoring and surveillance of SARS and respiratory viruses are important for health management, minimizing the impact of these respiratory infections. The present study was about the seasonality and clinical impact of respiratory viruses in children admitted to a pediatric reference hospital. The study included 229 children from 0 to 15 years old, from January 2012 to December 2015, with clinical diagnosis of SARS and respiratory sample collected and sent to the Central Laboratory of the State of Paraná for etiological agent analysis. The search for SARS cases was performed using the GSUS (Health Care Management of SUS) electronic filesystem, records of the center of physiotherapy and information of the Hospital Infection Control Center of the studied hospital. Of the patients included in the research, data collection forms were filled out and later analyzed according to the research objectives. Statistical analyzis were performed with the statistical package GRAPHPAD PRISM and a significance level of 5% was considered. The majority of patients in the sample belonged to the age group 0-6 months of age, and there was no predominant sex. Regarding the risk factors for viral infection, the presence of comorbidity or underlying disease was the most prevalent factor. In the present study, the positive samples for at least one etiological agent accounted for 76.41%, and the most prevalent virus was Respiratory Syncytial Virus (RSV). As for the seasonality of viral detection, there was a predominance in the late fall and early winter, which was more pronounced for RSV. When the environmental temperatures of the region were analyzed, the incidence of SARS was significantly higher in the descending quartile of the average minimum temperature. No significant difference was observed between the studied etiological groups in relation to the time from the beginning of the symptoms until the hospitalization. There was a predominance of hospitalizations in the Intensive Care Unit. The hospitalization time was significantly higher in patients with underlying disease or comorbidities and did not change according to the identified etiological agents or the presence of codetection. Patients who presented a mixed pattern on chest radiography had a significantly longer hospitalization time than those who had the interstitial infiltrate pattern. The total time was significantly lower in the Metapneumovirus group than in the Bordetella pertussis, Influenza, Rhinovirus and group of patients without detected infectious agents. Most patients were discharged from hospital, but there were three deaths due to SARS, all in patients with some underlying disease or risk conditions.

Introducción: El presente proyecto de intervención en salud se realizó en el asentamiento humano Pacífico Villa parte alta, ubicado en el distrito de Chorrillos, donde la prevalencia y mortalidad por enfermedades respiratorias en niños menores de 5 años es alta y representa un problema en salud. Objetivos: El proyecto tuvo el objetivo de mejorar el conocimiento de la población sobre la prevención de enfermedades respiratorias agudas en niños menores de 5 años. Para lograr esto se incidió en las principales 3 causas encontradas que eran los inadecuados hábitos de higiene en niños y cuidadores involucrados, la baja cobertura de vacunación en los niños menores de 5 años y la malnutrición en los niños que los predispone a padecer todo tipo de enfermedades. Metodología: Se siguió la metodología del marco lógico, se realizó en primer lugar una priorización de problemas y el análisis de involucrados, se esquematizó el árbol de problemas y árbol de objetivos, a continuación, se analizaron las alternativas de solución y se graficó la estructura analítica del proyecto, luego se realizó la matriz del marco lógico y finalmente se plantearon las actividades y tareas resumidas en la matriz de programación. Actividades: Se realizaron 2 actividades principales que consistieron en la realización de afiches y videos para presentar a la comunidad vía online debido a la coyuntura actual de la pandemia por Sars-CoV-2. Resultados: Los resultados del proyecto a corto plazo se midieron por encuestas de conocimiento respondidas por la comunidad, una antes de la intervención y otra después, siendo el logro final la mejora de conocimiento de la comunidad en materia de prevención de enfermedades respiratorias, reconocimiento de sus signos de alarma, importancia de la vacunación, alimentación saludable, métodos de higiene, lactancia materna, entre otros. / Introduction: This health intervention project was carried out in the Pacific Villa upper part human settlement, located in the district of Chorrillos, where the prevalence and mortality from respiratory diseases in children under 5 years of age is high and represents a health problem. Objectives: The project had the objective of improving the population’s knowledge about prevention of acute respiratory diseases in children under 5 years of age. To achieve this, the main 3 causes found were involved, which were inadequate hygiene habits in children and their caregivers, low vaccination coverage in children under 5 years of age and malnutrition in children that predisposes them to suffer all kinds of diseases. Methodology: The logical framework approach was followed, first a prioritization of problems and the analysis of those involved were carried out, the tree of problems and tree of objectives were outlined, then the solution alternatives were analyzed and the analytical structure of the project, then the logical framework matrix was made and finally the activities and tasks summarized in the programming matrix were proposed. Activities: Two main activities were carried out, which consisted of making posters and videos to present to the community online due to the current situation of the Sars-CoV-2 pandemic. Results: The results of the short-term project were measured by knowledge surveys answered by the community, one before the intervention and another after, the final achievement being the improvement of the community's knowledge in the prevention of respiratory diseases, recognition of its warning signs, the importance of vaccination, healthy eating, hygiene methods, breastfeeding, among others. / Tesis

This thesis investigates the possibilities of increasing efficacy and general improvement of unsupervised medical treatments by implementing electronics and embedded systems (so-called smart devices) to allow the physician to monitor or track the treatment and adherence of the patient to it. The diseases in focus are respiratory: asthma and Chronic Obstructive lung [Pulmonary] Disease (COPD). This thesis will furthermore attempt to show that shortcomings in the current treatment of these diseases incur significant human costs by loss of quality of life for the patients and causes (avoidable) costs to health-care systems and societies on a macro-economic scale, both direct and indirect. It will find that the technology to create a smart-inhaler exists, and while not a panacea, it can address many of the identified issues with the current mode of treatment.This thesis was written in partnership with SHL Medical AB, and the author wishes to extend specialthanks to Plamen Balkandjiev and Mattias Myrman for their help, support, and patience. / Detta examensarbete undersöker möjligheterna att öka effektiviteten samt allmänna förbättringar av oövervakad medicinsk behandling genom implementering av elektronik och inbyggda system (så kallade smarta-apparater) för att möjliggöra för läkare att övervaka eller följa behandlingen samt huruvida patienten fullföljer den eller ej. Sjukdomarna i fokus är astma och Kronisk Obstruktiv Lungsjukdom (KOL). Vidare kommer detta arbete försöka visa att tillkortakommanden i den befintliga behandlingen av sjukdomar inte bara medför signifikanta minskningar i livskvalitet för patienten utan även orsakar (icke oundvikliga) kostnader för sjukvårdssystem och samhällen på en makro-ekonomisk skala, indirekt såsom direkt. Den kommer även visa att tekniken som krävs för att skapa en smartinhalator existerar, och medans denna inte är en panacé kan den likväl åtgärda många av de identifierade problemen med den befintliga behandlingsmetoden.Detta exmanensarbete skrevs i samarbete med SHL Medical AB och dess författare önskar utsträckaett särskilt tack till Plamen Balkandjiev och Mattias Myrman för deras hjälp, stöd och tålamod.

Über die Ätiologie und Epidemiologie der Erkrankungen des Respirationstraktes im Frühneolithikum Mitteleuropas gibt es bislang keine umfassenden Studien. Die Häufigkeit, mögliche Geschlechts- und Altersunterschiede, Populationsunterschiede und Erkenntnisse über mögliche Ursachen und auslösende Faktoren der Atemwegserkrankungen zur Zeit der Bandkeramik sind von besonderem Interesse. Zudem soll aufgezeigt werden wie wichtig es ist, alle Strukturen zu untersuchen, die den „knöchernen Respirationstrakt“ repräsentieren. Von den ersten Ackerbauern und Viehzüchtern aus Wandersleben (Thüringen, Kreis Gotha) lagen insgesamt 112 erwachsene Individuen zur Untersuchung vor. Rippen und Schädel wurden mit paläopathologischen Methoden untersucht. Diese waren neben einer makroskopischen Begutachtung der Knochen, röntgenologische, endoskopische, lupenmikroskopische, lichtmikroskopische und rasterelektronenmikroskopische Untersuchungen, um eine verlässliche Diagnosestellung zu gewährleisten. 100 % (n = 71/71) der befundbaren Individuen zeigten Spuren chronischer Erkrankungen im Bereich der knöchernen Strukturen, die die oberen Atemwege umgeben. Bei 76,8% (n = 53/69) der Individuen mit befundbaren Rippen konnten Spuren von chronischen Erkrankungen aufgezeigt werden. Signifikante Geschlechts- oder Altersunterschiede bestehen insgesamt nicht. Bei der linearbandkeramischen Population aus Wandersleben ist davon auszugehen, dass es sich in vielen Fällen um Chronifizierungen von Erkältungskrankheiten und um die Folgen einer vergleichbar schlechten Luftqualität hauptsächlich im Haus handelt. Dazu haben die damaligen Lebensumstände, vor allem aber die sesshafte Lebensweise und Wirtschaftszweige mit Ackerbau und Viehzucht, maßgeblich beigetragen.