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Variants in the dihydropyrimidine dehydrogenase gene (DPYD) in patients with rectal cancer undergoing adjuvant 5-FU-based chemotherapy: A monocentric analysis from the GAST-05 study
No full textIn dieser monozentrischen posthoc Studie wurde der Einfluss des okkulten DPYD-Mutationsstatus bei Patienten mit Adenokarzinomen (Stadium ≥ II) im oberen Rektum unter 5-Fluorouracil (FU)-haltiger Chemotherapie (CTx) auf das Auftreten von CTC-AEs (Common-Toxicity-Criteria-Adverse-Events) Grad ≥ 3 untersucht. 75 Patienten (medianes Alter: 69 Jahre, F: 26, M: 49) der GAST-05-Phase-IIb Studie (ISRCTN35198481) waren beim prätherapeutischen Staging auf den DPYD*2A-Wildtyp (WT) getestet worden. Postoperativ erhielten 43 Patienten (Pat.) eine FOLFOX-CTx (4 Zyklen; FA: 400 mg / m², 5-FU: 2.400 mg / m², OX: 100 mg / m²). Nach Empfehlung der Europäischen Arzneimittelagentur (EMA) wurde auf DPYD*2A (c.1905+1G>A; IVS14+1G>A; rs3918290), DPYD*13 (c.1679T>G; rs55886062), den Polymorphismus c.2846A>T (rs67376798) und Haplotyp B3 (Hap B3; c.1236G>A; c.1129-5923C>G) getestet. Die maximale Toxizität (pro CTx-Zyklus) zwischen WT- und DPYD-mutierten Pat. wurde mit Fisher´s exact Test berechnet. Gemischte logistische Regressionsmodelle wurden angepasst, um die Auswirkungen von DPYD-Mutationen auf die CTC-AEs (hoch- vs. niedriggradig) zu untersuchen. Das Überleben der Pat. wurde mit Hilfe des Kaplan-Meier-Schätzers und des Logrank-Tests berechnet. Die DPYD-Untersuchung ergab 100% WT für DPYD*2A, DPYD*13 und den Polymorphismus c.2846A>T. Bei 5 Pat. wurde ein okkulter heterozygoter (het) DPYD-Hap B3-Status festgestellt. Bei allen 43 Pat. (38x WT, 5x het_Hap B3), die mit FOLFOX behandelt wurden, lag die Adhärenz gegenüber den CTx Zyklen 1 bis 4 bei 100%, 97,7%, 95,3% und 93,0%. Bei den WT-Pat. betrug die applizierte Dosis von 5-FU und OX 92,6% und 75,3%, bei den het_Hap B3-Pat. 68,8% und 55,0% der Zieldosis. Im Vergleich zur WT Kohorte hatten die het_Hap B3-Pat. ein 2,43-fach höheres relatives Risiko für höhergradige CTC-AEs (Grad ≥ 3) und ein verkürztes DFS (p = 0,010; Nachbeobachtung: 101 Monate im Median). Die posthoc Testung bei DPYD*2A-WT GAST-05-Patienten ergab in > 11% einen bis dahin unbekannten het_Hap B3-Status.In this monocentric posthoc study the impact of occult mutational DPYD status in patients with adenocarcinomas (stages ≥ II) of the upper rectum was investigated towards the occurrence of CTC-AEs (Common-Toxicity-Criteria-Adverse-Events) grades ≥ 3 associated with 5-Fluorouracil (FU) chemotherapy (CTx). 75 patients (pts) (median age: 69 yrs, f: 26, m: 49) of the GAST-05-phase-IIb-trial (ISRCTN35198481) had been tested for DPYD*2A-wildtype (WT) at staging. After upfront surgery, FOLFOX-CTx (4 cycles; FA: 400 mg / m², 5-FU: 2.400 mg / m², OX: 100 mg / m²) was applied in 43 pts DPYD-testing was performed for evaluation of DPYD*2A (c.1905+1G>A; IVS14+1G>A; rs3918290), DPYD*13 (c.1679T>G; rs55886062), the polymorphism c.2846A>T (rs67376798) and Haplotype B3 (Hap B3; c.1236G>A; c.1129-5923C>G) according to recent EMA recommendations. Maximal toxicity (per CTx cycle) was compared between WT vs DPYD mutational pts using Fisher’s exact test. Mixed logistic regression models were fit to study the effect of DPYD mutations on CTC-AEs (high vs low grade). Survival was calculated using the Kaplan-Meier estimator and compared between groups using the logrank-test. DPYD re-testing revealed 100% WT for DPYD*2A, DPYD*13 and the polymorphism c.2846A>T. Interestingly, in 5 pts an occult heterozygous (het) DPYD Hap B3 status was detected. For all 43 pts (38x WT, 5x het_Hap B3) receiving FOLFOX, the adherence to CTx cycle number 1 to 4 was 100%, 97.7%, 95.3% and 93.0%, respectively. For WT pts the administered dosages of 5-FU and OX were 92.6% and 75.3%, and for het_Hap B3 pts 68.8% and 55.0% of the target dose, respectively. Compared to the WT cohort, the relative risk (RR) for severe CTC-AEs (grades ≥ 3) was 2,43 for het_Hap B3 pts. These pts were associated with limited DFS (p = 0.010, follow-up: 101 months in median).2025-04-3
Measurement of top quark pair production in association with charm quarks at √s = 13 TeV with the ATLAS detector
Get PDFThe Large Hadron Collider at CERN has produced a uniquely large set of proton-proton collision data at never-before-seen energies since the beginning of its operation in 2010.
Using data collected by the ATLAS detector at a centre-of-mass energy of between 2015 and 2018, corresponding to an integrated luminosity of , this thesis presents the results of the first dedicated ATLAS measurement of the production cross-section of top quark pairs in association with charm quarks. This measurement tests and provides information for future improvements of the modelling in quantum chromodynamics of systems which act at multiple distinct energy scales. This process is also an important background to measurements of other, much rarer, top quark processes such as {()} and .
A key challenge of this measurement is the simultaneous identification of - and -jets, for which a custom heavy-flavour tagging algorithm is employed. A profile likelihood fit is used to extract the cross-sections for top quark pairs in association with two or more -jets () and with one -jet (). This measurement is performed both in a fiducial phase space designed to mimic the acceptance of the ATLAS detector, and in a more inclusive phase space. In the fiducial phase space this measures cross-sections of and for and production, respectively. An additional fit extracts the ratios of and cross-sections to that of total jets production. The measured values tend to exceed predictions from simulation, but nonetheless are consistent with them within 0.5 to 2 standard deviations. Sensitivity is ultimately limited by uncertainties in the modelling of the system, as well as in the calibration of the heavy-flavour tagging algorithm and by limited data statistics. A focus is placed in this thesis on the work done to validate and understand the fit model.2025-06-0
Entgiftung bei Alkoholabhängigen mit Clomethiazol oder Diazepam - Vergleich von Behandlungsvariablen
No full textBackground: Current guidelines on alcohol-related disorders recommend pharmacological treatment of alcohol withdrawal syndrome (AWS) based on symptom severity. In Germany, benzodiazepines—particularly diazepam—or clomethiazole are commonly used in inpatient care. This study aimed to compare the efficacy of diazepam and clomethiazole in the treatment of AWS.
Methods: A retrospective analysis of 160 inpatient AWS cases was conducted (84 treated with diazepam, 76 with clomethiazole). The variables analyzed included duration of inpatient treatment, symptom severity and medication dosage. Statistical significance was assessed using the chi-square test (p<0.05). To assess the influence of combined benzodiazepine and alcohol withdrawal treatments on the results, a secondary analysis was performed excluding such combined treatments.
Results: Diazepam was prescribed for a significantly longer duration, and the total administered dose was higher compared to clomethiazole. After excluding combined withdrawal cases, the difference in treatment duration remained significant, while the difference in total dosage did not.
Conclusion: Both diazepam and clomethiazole are effective in managing AWS. Treatment choice often depends on individual patient factors. Clomethiazole may offer shorter treatment durations, but further studies with larger, more homogeneous populations are needed to confirm this result.2025-07-2
Self-determined action at the end of life – autonomy and trust in the interaction dynamics of patients and their relatives
No full textVolkswagen StiftungAngehörige sind neben der ärztlichen Betreuung ein wichtiges Fundament für die Patientenautonomie. Am Lebensende ist für die Erkrankten selbstbestimmtes Handeln nur mit Unterstützung – sei es bei alltäglichen Aufgaben oder bei der mentalen Begleitung – möglich. Inwieweit eine Wechselwirkung von Vertrauen, Bedürfnissen, Handlungsstrategien und selbstbestimmten Entscheidungen in der Interaktionsdynamik zwischen Patient*innen und Angehörigen besteht, wird in der vorliegenden Studie wissenschaftlich untersucht.
Im Rahmen einer qualitativen Studie wurden biographisch-narrative Interviews mit Patient*innen (n=6) und narrative Interviews mit Angehörigen (n=6) geführt. Davon wurde eine Stichprobe von drei Paaren ausgewählt. Die Analyse der transkribierten Interviews erfolgte anhand der Grounded Theory nach Strauss und Corbin.
Als zentrales Ergebnis ist das Kernphänomen Krankheitsadaptierendes Erleben hervorzuheben. Dieses ist sowohl bei Patient*innen wie auch Angehörigen festzustellen und steht im Kontext von Vertrauen. Vertrauen – interpersonales Vertrauen in Ärzt*innen und vor allem in die Paarbeziehung, aber auch Selbstvertrauen in die eigene Person – ist ab der Diagnosestellung sicherheitsspendendes Fundament. Das Krankheitsadaptierende Erleben befasst sich im Wesentlichen mit dem Umgang von Erkrankung am Lebensende und nimmt Einfluss auf eigene Bedürfnisse und Erwartungen an den jeweils anderen. Bei selbstbestimmten Entscheidungen am Lebensende setzen Patient*innen
ärztlicherseits angebotene lebenszeitverlängernde Therapien in Relation zur subjektiven Lebensqualität. Diese persönliche Entscheidung wird dann in Relation zur Umwelt gesetzt, insbesondere dann, wenn Angehörige die getroffene Entscheidung nicht mittragen und das rankheitsadaptierende Erleben von Patient*innen mit dem Krankheitsadaptierenden Erleben ihrer Angehörigen in Konflikt gerät. Im Spannungsfeld von verbalen und nonverbalen Auseinandersetzungen ändern Patient*innen unter Umständen ihre initiale Entscheidung.
Weiterhin ist festzustellen, dass Angehörige in der Interaktionsdynamik oftmals ihre eigenen Bedürfnisse zur Umsetzung der Bedürfnisse des erkrankten Partners zurückstellen. Dies zeigt sich insbesondere in der Anpassung und Neugestaltung des alltäglichen Lebens. Daran lässt sich eine Rollenumverteilung, begründet in den veränderten körperlichen und kognitiven Kapazitäten des erkrankten Partners, feststellen. Dies birgt die Gefahr der Be- bis Überlastung von Angehörigen, was ein weiterer einflussnehmender Faktor auf selbstbestimmte Entscheidungen am Lebensende ist. Hier werden Entscheidungen der Patient*innen zu Gunsten der Entlastung ihrer Angehörigen, zum Beispiel
durch Nutzen von Pflegediensten oder Pflegeeinrichtungen, getroffen.
Die Entwicklung und Ausgestaltung des Krankheitsadaptierenden Erlebens, sowohl von Patient*innen als auch ihren Angehörigen, von der Diagnosestellung bis zum Lebensende ist nicht statisch, sondern prozesshaft, weil selbstbestimmtes Handeln und selbstbestimmte Entscheidungen immer auch in sozialen Strukturen stattfinden.
Damit Selbstbestimmung am Lebensende gelingen kann, sollten divergente Wahrnehmungen von Krankheitsadaptierendem Erleben frühzeitig bei Behandlungsentscheidungen wahrgenommen werden und angeleitet offen kommuniziert werden. Je mehr Unterstützung Angehörige systemseitig bei Pflege und Alltag mit ihren erkrankten Partner*innen erhalten, desto freier können Patient*innen ihre Entscheidungen anhand individueller Bedürfnisse für ihr Lebensende treffen.In addition to medical care, family members are an important foundation for patient autonomy. At the end of life, patients can only act independently with support—be it in everyday tasks or in mental support. This study scientifically investigates the extent to which trust, needs, action strategies, and self-determined decisions interrelate in the interaction dynamics between patients and family members.
As part of a qualitative study, biographical-narrative interviews were conducted with patients (n=6) and narrative interviews with family members (n=6). A sample of three pairs was selected. The analysis of the transcribed interviews was conducted using Strauss and Corbin's grounded theory.
The key finding is the core phenomenon of illness-adaptive experience. This can be observed in both patients and family members and is related to trust. Trust – interpersonal trust in physicians and especially in the relationship, but also self-confidence – is a foundation of security from the moment of diagnosis. Disease-adaptive experience essentially deals with how patients cope with illness at the end of life and influences their own needs and expectations of each other. When making self-determined decisions at the end of life, patients compare the life-prolonging therapies offered by doctors with their subjective quality of life. This personal decision is then placed in relation to the environment, especially when relatives do not support the decision made and the patient's disease-adaptive experience conflicts with the disease-adaptive experience of their relatives. In the tension between verbal and nonverbal conflicts, patients may change their initial decision.
Furthermore, it can be observed that relatives often put their own needs aside in the dynamics of interaction to meet the needs of their sick partner. This is particularly evident in the adaptation and reorganization of everyday life. This reveals a redistribution of roles, rooted in the altered physical and cognitive capacities of the sick partner. This poses the risk of burdening or even overburdening relatives, which is another factor influencing self-determined decisions at the end of life. Patients' decisions are made to relieve the burden on their relatives, for example, by using care services or nursing facilities.
The development and design of the disease-adaptive experience, both of patients and their relatives, from diagnosis to the end of life, is not static but rather processual, because self-determined actions and self-determined decisions always take place within social structures.
For self-determination at the end of life to succeed, divergent perceptions of disease-adaptive experience should be recognized early in treatment decisions and openly communicated under guidance. The more systemic support relatives receive in caring for and in everyday life with their sick partners, the more freely patients can make their decisions based on their individual needs for the end of their lives.2025-07-3
Cell-type specific roles of long non-coding RNAs in Neurodegenerative diseases
No full textLong non-coding RNAs (lncRNAs) are a heterogeneous group of RNAs that occupy a substantial proportion of the genome and are intricately involved in the regulation of various cellular processes. A notable feature of lncRNAs is their high cell- and tissue- specificity, and emerging evidence suggests that lncRNAs can play unique roles in individual cell-types. The specificity of lncRNAs is particularly noteworthy in the brain tissue as approximately 40% of the lncRNAs are predicted to be brain specific in expression. In the ageing brain, there are drastic changes at the cellular and molecular level that contribute to the age-related cognitive decline. Consequently, ageing is the primary risk factor for neurodegenerative diseases (NDDs) including Alzheimer’s disease (AD). Despite several studies describing the cell-type specific roles of lncRNAs in the brain, there is currently, limited information on the role of lncRNAs in the ageing- and AD- brain. lncRNAs provide a largely unexplored window into cellular functions in the healthy and diseased brains and offers a novel opportunity for the discovery of biomarkers and therapeutic targets for age-related NDDs like AD.
My doctoral work was aimed at evaluating the roles of lncRNAs in a cell-type specific manner in the ageing- and AD- brain. To accomplish this, I identified and characterized two lncRNAs during my doctorate that are presented as two manuscripts in this dissertation. In the first manuscript, I describe a novel neuron-specific lncRNA that we named as “NeuID” (abbreviation for Neuronal Identity). NeuID was observed to be a neuron-specific and brain enriched lncRNA that is decreased in the brains of AD patients. NeuID possessed a human homolog and played a role in the regulation of gene-expression in neurons. Specifically, NeuID knockdown (KD) decreased the levels of synaptic genes in neurons and upregulated non-neuronal genes. The decrease in synaptic genes upon NeuID KD was consistent with the reduced neuronal activity and decreased dendritic spines and synapse density of primary hippocampal neurons. The changes in synaptic plasticity elicited by NeuID KD further resulted in impairment of memory consolidation in mice. These findings suggest that NeuID regulates synaptic plasticity through transcriptomic control of synaptic genes, and this in turn regulates memory formation in mice. I found NeuID to be decreased in the brains of AD patients and further observed that NeuID expression is negatively correlated with progressive Braak & Braak stages of AD pathology. Based on these observations, I studied the roles of NeuID in neuronal cells in the context of amyloid beta (Aβ) based AD-pathology. Aβ-exposure resulted in the reduction of NeuID levels in neurons and decrease in neuronal activity comparable to the findings in NeuID KD neurons. Overexpression of NeuID using CRISPRa resulted in the rescue of Aβ-mediated neuronal activity changes. Mechanistically, NeuID binds to the PRC2 complex subunit EZH2 to regulate h3k27me3-levels of non-neuronal genes. Decrease in h3k27me3 levels at the non-neuronal gene loci leads to the upregulation of non-neuronal genes. The upregulation of non-neuronal genes in neurons due to NeuID KD is contributing to the observed neuronal function impairment. Overall, this study identifies, to the best of my knowledge, the first neuron-specific lncRNA that is involved in the regulation of neuronal function in the context of AD. Additionally, NeuID provides an opportunity for the development of a lncRNA mediated therapy against neuronal pathology in AD.
The second manuscript in this dissertation is focused on an ageing-related lncRNA named “3222401L13Rik”, and here I describe the functions of this lncRNA in microglia cells in the context of ageing and AD. 3222401L13Rik was observed to be increased in the glial cells of the aged mice brain. It was further increased in expression in aged microglia cells based on the single-cell ageing mouse brain database. 3222401L13Rik also has a human homolog named “ENSG00000272070” which shows decreased levels in the brains of AD patients. Both 3222401L13Rik and ENSG00000272070, upon KD, increased the expression of proinflammatory cytokine “TNF” in microglia cells of mice and human origin respectively. The elevated expression of TNF was consistent with the observed increase in the phagocytic activity of microglia. The transcriptomic changes elicited in primary microglia and human derived iPSC microglia like cells (iMGLs) were comparable to the transcriptomic changes in the AD brain. Consequently, the KD of the lncRNA in primary microglia and iMGLs increased the engulfment of pathologic Aβ due to the increased phagocytic activity of microglia. Mechanistically, the lncRNA binds to the AD-associated TF PU.1, and the transcriptomic changes in microglia induced by PU.1 activity are similar, at least in part, to the transcriptomic changes elicited by 3222401L13Rik. In conclusion, these findings identify an ageing-related lncRNA that regulates microglia function through interaction with AD-associated TF PU.1. This lncRNA reveals a novel molecular mechanism behind PU.1 function in microglia, and lncRNA mediated regulation of PU.1 function could be a potential means to target microglia pathology in AD. In the context of ageing, I speculate that the increased levels of 3222401L13Rik in the ageing brain and microglia might play a protective role in healthy ageing by attenuating the levels of proinflammatory cytokines and microglia activity.
In summary, this dissertation demonstartes the roles that lncRNAs play in specific cell-types in the brain, and adds to the growing literature of lncRNA involved in brain function. Moreover, these findings demonstrate a link between lncRNAs and AD-related cellular impairments, therefore, providing a yet unexplored avenue for therepautic intervention in AD.2025-07-2
CRISPR/Cas9 Activation of Delta-like non-canonical Notch ligand 1 (DLK1) to Protect from Contractile Dysfunction in Engineered Human Myocardium
No full textDeutsches Zentrum für Herz- und KreislaufforschungDelta-like non-canonical Notch ligand 1 (DLK1) is a gene that is highly upregulated in all three germ layers during the development of the human body, but is almost absent in end-stage heart failure. This work confirmed the decreased DLK1 expression in a heart failure phenotype in vivo and in vitro. We mimicked neurohormonal stress in monolayer induced pluripotent stem cell-derived cardiomyocytes by supplementation of Transforming Growth Factor-β1 or L-noradrenaline for 3 days, demonstrating diminished DLK1 expression upon stress. To reactivate the DLK1 expression in vitro, we utilized a Clustered Regularly Interspaced Short Palindromic Repeats activation (CRISPRa). Lentiviral gene delivery of our tested guide ribonucleic acid E was utilized to transduce induced pluripotent stem cell-derived cardiomyocytes. To further validate the successful reactivation on the protein level, we applied the Western blot technique, demonstrating sufficient DLK1 overexpression. As we observed that DLK1 protein abundance in human serum samples is abolished in heart failure, we analyzed supernatants of monolayer induced pluripotent stem cell-derived cardiomyocytes after CRISPR mediated DLK1 enhancement. Concordantly, we saw increased DLK1 protein abundance in our samples. To further study functional effects mediated by cardiomyocyte specific DLK1 activation, we used our established Engineered Human Myocardium model. DLK1 activated Engineered Human Myocardium displayed functional differences in their contractile force generation compared to their respective controls. Furthermore, we demonstrated that increased preloading of Engineered Human Myocardium improved functional maturation. To recapitulate a heart failure phenotype in Engineered Human Myocardium, we applied neurohormonal stress for 1 week by daily supplementation of Transforming Growth Factor-β1 and L-noradrenaline. Engineered Human Myocardium with CRISPR enhanced DLK1 transcription is partially protected from NAT induced contractile dysfunction. We further elucidated transcriptomic changes and found evidence for enhanced mitotic activity. From our data, we conclude that DLK1 induces a pro-regenerative program, preventing contractile deterioration. In accordance with the recent literature, we observed an influence of DLK1 activation on Transforming Growth Factor-β1 signaling. An inhibitory role of DLK1 on Notch signaling was not detected. Perspectively, DLK1 is a promising target to rejuvenate the heart and ameliorate contractile function loss in heart failure.2025-07-1
Structural finger-jointing of European beech and birch – Studies on the joining and bonding mechanisms
No full textIn der Vergangenheit wurde die Keilzinkung von Laubhölzern im Vergleich zu
Nadelhölzern weniger erforscht und genormt. Dies ist mit mangelnden Kenntnissen und
Unsicherheiten bei der Herstellung von tragenden, auf Laubholz basierenden Holzwerkstoffen,
verbunden. Der Schwerpunkt der Untersuchungen in dieser Dissertation lag auf der tragenden
Keilzinkung der europäischen Laubholzarten Rotbuche (Fagus sylvatica, L., kurz Buche) und
Moorbirke (Betula pubescens, Ehrh.) sowie Hängebirke (Betula pendula, Roth), kurz Birke. Mittels
einer semi-industriellen Keilzinkenanlage für Kurzholz und handelsüblicher Klebstoffsysteme
wurden verschiedene Parameter hinsichtlich der Füge- und Verklebungsmechanismen
untersucht. Die wissenschaftlichen Veröffentlichungen dieser Dissertation befassten sich mit
der Bestimmung und Bewertung der Delaminierungsbeständigkeit von Buchen-
Keilzinkenverbindungen (Publication I), der Charakterisierung des Fügeverhaltens in
Abhängigkeit von der Holzart und der Feuchtebelastung (Publication II) und der Analyse der
Oberflächeneigenschaften von Keilzinkenverbindungen in Abhängigkeit vom Fräsprozess
(Publication III). Weiterhin wurden die Verklebungsfestigkeit und die elasto-mechanischen
Eigenschaften von Laubholz-Keilzinkenverbindungen bestimmt (Publication IV und
Publication V), die Keilzinkengeometrie angepasst und die elasto-mechanischen Eigenschaften
angepasster Keilzinkenverbindungen ermittelt (Publication VI und Publication VII). Darüber
hinaus wurden Keilzinkenverbindungen in weiteren Laubholzwerkstoffen charakterisiert
(Publication VIII). Die Ergebnisse dieser Studien sollen als Grundlage für die Herstellung und
für Anpassungen im Zusammenhang mit tragenden Laubholz-Keilzinkenverbindungen
dienen. Insgesamt wurde in dieser Arbeit festgestellt, dass sich Buche und Birke aufgrund ihrer
ähnlichen physikalischen und anatomischen Eigenschaften bei der Keilzinkenverbindung sehr
ähnlich verhalten. Es wurde bestätigt, dass ihre höhere Dichte der Faktor ist, der sie am meisten
von den Nadelhölzern unterscheidet und bei ihrer Keilzinkung berücksichtigt werden muss. In
der Publication I erfüllten die PRF verklebten Buchen-Keilzinkenverbindungen die
Normanforderungen der Delaminierungsprüfung, während die MUF Verklebungen die
Normanforderungen nicht erfüllten. PUR verklebte Keilzinkenverbindungen waren
beständiger gegen Delaminierung, wenn das Holz mit einem höheren Feuchtigkeitsgehalt
verklebt wurde. Die Publication II zeigte die hohe Bedeutung der Selbsthemmung für die
Anfangsfestigkeit der Keilzinkenverbindung und für die Ausbildung der Klebefuge. Es wurde
festgestellt, dass Holzarten mit höherer Dichte dazu neigen, sich weniger zu verdichten als
Holzarten mit niedriger Dichte, wenn sie keilgezinkt werden. Die Verdichtung schien bei den
Holzarten mit höherer Dichte, Buche und Birke, in Richtung der Zinkenspitze des
Keilzinkenprofils zuzunehmen, während die Verdichtung im Keilzinkenprofil der Pappel eher
konstant war. Es wurde festgestellt, dass die Passgenauigkeit des Keilzinkenprofils von großer
Bedeutung ist und sich bei Laubhölzern noch stärker auswirkt als bei Nadelhölzern.
Verformungen in Folge von Änderungen der relativen Luftfeuchtigkeit wirkten sich negativ
auf die Selbsthemmung von Buchen-Keilzinkenverbindungen aus. Die Publication III
verdeutlichte die Komplexität der Keilzinkenoberfläche nach verschiedenartigen
Fräsprozessen und dass die Oberfläche durch die Wahl der Bearbeitungsparameter beeinflusst
werden kann. Der Zusammenhang zwischen der Leistungsfähigkeit und der Gestaltung der
Keilzinkenoberfläche ist jedoch nicht untersucht worden. Bei den getesteten Klebstoffsystemen
waren die Festigkeiten der Keilzinkenverbindungen von Buche und Birke höher als bei
herkömmlichen Nadelholz-Keilzinkenverbindungen. PUR Verklebungen erreichten
tendenziell etwas geringere Keilzinkenfestigkeiten als PRF und MUF Verklebungen
(Publication IV und Publication V). Zusammenfassend wurde in dieser Arbeit die hohe Relevanz der Klebstoffauswahl für die tragende Laubholz-Keilzinkung deutlich. Für die hohe Festigkeit, hohe Steifigkeit und geringe Dimensionsstabilität (z.B. Buche) der Laubhölzer sind leistungsfähige Klebstoffsysteme erforderlich. Die anatomische Struktur und die chemische Zusammensetzung der Laubhölzer sollten bei der Formulierung des Klebstoffs und bei dessen Verarbeitung berücksichtigt
werden. Frühere Studien (erörtert in Publication IV und Publication V) haben die Schwächen der
heutigen tragenden Keilzinkenverbindungen aufgezeigt, insbesondere für hochfeste
Laubhölzer. Im Rahmen dieser Dissertation wurde ein neuartiges Keilzinkenprofil entwickelt,
das bei Buche und Birke zu hohen Keilzinkenfestigkeiten führte, die über denen herkömmlicher
Keilzinkenprofile lagen. Die generelle Machbarkeit der Keilzinkung wurde in dieser Arbeit für
viele Werkstoffe nachgewiesen.In the past, the finger-jointing of hardwoods was less researched and standardised compared
to softwoods. This is associated with a lack of knowledge and uncertainties in the production
of load-bearing hardwood engineered wood products (EWPs, used synonymously with
building products). The focus of the studies of this dissertation was set on the structural finger-
jointing of the European hardwood species beech (Fagus sylvatica, L.) and
birch (Betula pubescens, Ehrh. and Betula pendula, Roth). Various parameters regarding the
joining and bonding mechanisms were investigated using a commercial finger-jointing line for
short pieces of wood and commercial adhesive systems. The scientific publications of this
doctoral thesis addressed the determination and evaluation of the delamination resistance of
beech finger joint bondings (Publication I), the characterisation of the joining behaviour
depending on the wood species and exposure to varying relative humidity (Publication II) and
the analysis of surface properties related to finger joint bonding depending on the cutting
process (Publication III). Furthermore, the bonding strength and elasto-mechanical properties
of hardwood finger joints were determined (Publication IV and Publication V), the finger joint
geometry adjusted and the elasto-mechanical properties of adjusted finger joints determined
(Publication VI and Publication VII). In addition, finger joints in further hardwood-based
materials were characterised (Publication VIII). The results of these studies are intended to
serve as a basis for the production and for adaptations related to structural hardwood
finger joints. Overall, this thesis found that beech and birch behave very similarly in finger-
jointing due to their similar physical and anatomical properties. It was confirmed that their
higher density is the factor that most distinguishes them from softwoods and must be
considered when finger-jointing. In Publication I the normative requirements of the resistance
to delamination test were met by PRF bonded beech finger joints, whereas the MUF bondings
did not meet the standard requirements. PUR bonded finger joints were more resistant to
delamination when wood with a higher moisture content was bonded. Publication II showed
the high relevance of self-locking for the initial strength of the finger joint and for the formation
of the bondline. It was found that higher-density wood species tend to densify less than low-
density wood species, when finger jointed. Densification appears to increase towards the tip of
the finger joint in the higher-density wood species beech and birch, whereas densification in
the poplar finger joint tended to be more constant. The accuracy of fit of the finger joint profile
was found to be highly relevant and even more for hardwoods than for softwoods.
Deformations due to varying relative humidity’s had a negative effect on the self-locking of
beech finger joints. The Publication III highlighted the complexity of the finger joint surface
after different mechanical treatment, and that the surface can be influenced by the choice of
machining parameters. However, the relation between the performance and the design of the
finger joint surface has not been investigated. With the adhesive systems tested, beech and birch
finger joint strengths were higher compared to conventional softwood finger joints. PUR bonds
tended to achieve slightly lower finger joint strengths than PRF and MUF bonds
(Publication IV and Publication V). In summary, the high relevance of the adhesive selection
for the structural hardwood finger-jointing became evident in this thesis. High-performance
adhesive systems are necessary for the high strength, high stiffness and low dimensional
stability (e.g. beech) of the hardwoods. The anatomical structure and chemical composition of
the hardwoods should be considered when formulating the adhesive, as well as the further
processing. Previous studies (discussed in Publication IV and Publication V) have highlighted the
weaknesses of today's structural finger joints, especially in the high strength range of
hardwoods. A novel finger joint profile was developed as part of this dissertation, resulting in
beech and birch finger joint strengths that were higher compared to conventional finger joint
profiles. The general feasibility of finger-jointing has been demonstrated for many materials in
this thesis.2025-08-2
Maize Root Colonization by Trichoderma virens: Mechanisms of Defense against Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) and Implications for Multi-Trophic Interactions
No full textThe work was made possible with the support of a scholarship from the German Academic Exchange Service (DAAD).Zusammenfassung
Trichoderma-Arten sind als wurzelbesiedelnde Pilze bekannt, die die pflanzliche Resistenz gegenüber biotischen und abiotischen Stressfaktoren stärken und gleichzeitig das Pflanzenwachstum fördern. Diese Pilze produzieren eine Vielzahl von volatilen und nicht-nicht-volatilen Metaboliten, die in der Pflanze verschiedene Interaktionen vermitteln und sowohl direkte als auch indirekte Abwehrmechanismen beeinflussen. Trichoderma kann die direkte pflanzliche Abwehr gegenüber Herbivoren verstärken und die Emission von herbivor-induzierten Pflanzenvolatilen (HIPVs) modulieren, welche die natürlichen Feinde anlocken. Frühere Studien haben gezeigt, dass T. virens und dessen vir4-Knockout-Mutante (defizient in der Sesquiterpen-Biosynthese) die Genexpression und die Synthese spezialisierter Metaboliten in Maiswurzeln unterschiedlich beeinflussen. Aufgrund dieser metabolischen Veränderungen wurde die Hypothese aufgestellt, dass eine Besiedelung der Pflanzenwurzeln durch den Pilz kaskadierende Effekte auf höheren trophischen Ebenen auslösen könnte. Diese Dissertation untersucht, wie T. virens und seine vir4-Mutante die Abwehrreaktionen von Mais beeinflussen – mit besonderem Fokus auf volatilen und nicht-volatilen Metaboliten, phytohormonellen Signalwegen sowie deren Auswirkungen auf tritrophische Interaktionen mit dem Herbivor Helicoverpa armigera und dem Prädator Macrolophus pygmaeus. Zusätzlich wird die Bioaktivität sesquiterpenbasierter T. virens-Metaboliten auf die Entwicklung des Herbivors bewertet.
Kapitel 1 befasst sich mit der Wirkung der Wurzelkolonisation durch T. virens auf die Fitness von H. armigera, potenzielle Veränderungen der HIPV-Emissionen sowie deren Einfluss auf die Anlockung von Prädatoren in Olfaktometer-Assays. Unsere Ergebnisse zeigen, dass Larven von H. armigera, die sich von Mais ernährten, der mit dem Wildtyp von T. virens kolonisiert war, signifikant weniger Gewicht zulegten als Larven auf mit der vir4-Mutante kolonisierten oder nicht kolonisierten Pflanzen. Dies deutet darauf hin, dass das vir4-Gencluster zur Resistenz gegenüber Herbivoren beiträgt. Obwohl die Pilzbesiedelung moderate Veränderungen in der HIPV-Zusammensetzung hervorrief, blieben die Gesamtmenge der Volatilemissionen unbeeinflusst. Zudem zeigte M. pygmaeus in Y-Typ-Olfaktometer-Assays eine klare Präferenz für durch Herbivorie geschädigte Pflanzen gegenüber solchen, die nicht geschädigt waren, wobei die Pilzbesiedelung keinen signifikanten Einfluss auf die Prädatorenanziehung hatte. Diese Ergebnisse zeigen, dass T. virens die direkte Abwehrfähigkeit von Mais gegenüber H. armigera verbessert, während indirekte Verteidigungsmechanismen aufrechterhalten bleiben.
Kapitel 2 untersucht die Auswirkungen der Pilzbesiedelung auf nicht-volatile Abwehrmechanismen, einschließlich spezialisierter und primärer Metaboliten sowie phytohormoneller Signalwege. HPLC-MS Analysen ergaben, dass Benzoxazinoide– die Hauptklasse sekundärer Maismetaboliten – sowie die phenolische Verbindung Chlorogensäure vorwiegend durch Herbivorie induziert wurden und nur geringfügig durch den Pilz beeinflusst waren. Ein ähnliches Muster zeigte sich bei den Phytohormonen, wobei auch hier die Herbivorie der Hauptauslöser hormoneller Veränderungen war. Dennoch ergab das Metabolomics-Profiling deutliche Verschiebungen im Metabolitenspektrum von Pilz-inokulierten Keimlingen, insbesondere bei solchen, die vom Wildtyp kolonisiert waren. Die Herbivorie verstärkte diese metabolischen Unterschiede zusätzlich. Auch Primärmetaboliten wurden durch Pilzbesiedelung und Herbivorie unterschiedlich beeinflusst. Diese Ergebnisse untermauern unsere früheren Beobachtungen, dass die Leistungsfähigkeit von H. armigera-Larven in Wildtyp-besiedelten Sämlingen signifikant reduziert war, was die Rolle des vir4-Gens von T. virens bei der Hochregulierung bestimmter metabolischer Merkmale in Mais hervorhebt. Diese führten letztlich zur verstärkten Resistenz gegen den Herbivoren.
Kapitel 3 befasst sich mit der Extraktion und Reinigung von Heptelidsäure und Hydroheptelidsäure aus dem Wildtyp von T. virens und deren larvizider Wirkung auf H. armigera. Die Ergebnisse zeigen, dass Heptelidsäure das Larvenwachstum signifikant hemmte und in den getesteten Konzentrationen eine insektizide Wirkung entfaltete. Im Gegensatz dazu zeigte Hydroheptelidsäure nur geringe larvizide Aktivität. Diese Befunde unterstreichen das Potenzial T. virens-abgeleiteter Sekundärmetaboliten als vielversprechende Kandidaten für eine nachhaltige und umweltfreundliche Schädlingsbekämpfung.
Insgesamt vertieft diese Dissertation unser Verständnis darüber, wie T. virens die chemische Abwehr von Mais beeinflusst und welche weitreichenden Effekte daraus in einem multitrophischen Kontext entstehen. Die Ergebnisse verdeutlichen, dass die pilzinduzierte pflanzliche Resistenz maßgeblich durch das vir4-Biosynthesegen von T. virens vermittelt wird, und heben die zentrale Rolle dieser Pflanze-Pilz-Symbiose für die Verbesserung der Pflanzenresistenz im Rahmen eines nachhaltigen Pflanzenschutzes hervor. Zudem betont die Arbeit das Potenzial von T. virens als Quelle wertvoller bioaktiver Sekundärmetaboliten mit Bedeutung für eine zukunftsfähige Schädlingsbekämpfung.Summary
Trichoderma spp. are widely recognized as root-colonizing biocontrol agents that enhance plant resistance to biotic and abiotic stresses while promoting growth. These fungi produce a diverse array of volatile and non-volatile metabolites that mediate interactions with plants, influencing both direct and indirect defense mechanisms. Trichoderma can enhance direct plant resistance against herbivores and modulate the emission of herbivore-induced plant volatiles (HIPVs) that attract natural enemies. Previous studies have demonstrated that T. virens and its vir4 knockout mutant (deficient in sesquiterpene biosynthesis) differentially influence maize (Zea mays L.) root gene expression and specialized metabolites. Given these metabolic alterations, we hypothesized that fungal root colonization could have cascading effects on higher trophic levels. This dissertation investigates how T. virens and its vir4 mutant influence maize defense responses, focusing on volatile and non-volatile metabolites and phytohormonal signaling pathways, and their subsequent effects on tri-trophic interactions involving the herbivore Helicoverpa armigera and the predator Macrolophus pygmaeus. Additionally, we assess the bioactivity of T. virens-derived, sesquiterpenes-based metabolites on herbivore performance.
Chapter 1 examines the impact of T. virens root colonization on H. armigera performance, as well as potential alterations in HIPV emissions and their ultimate influence on predator attraction in olfactometer assays. Our findings indicate that H. armigera larvae feeding on maize colonized by wild-type T. virens gained significantly less weight compared to those feeding on plants colonized by the vir4 mutant or uncolonized controls, suggesting that the vir4 gene cluster contributes to herbivore resistance. Although fungal colonization induced moderate changes in HIPV composition, total volatile emissions remained unaffected. Furthermore, in Y-tube olfactometer assays, M. pygmaeus displayed a strong preference for herbivore-damaged maize over undamaged plants, but fungal colonization had no significant impact on predator attraction. These results demonstrate that T. virens enhances maize's direct resistance against H. armigera while maintaining indirect defense mechanisms.
Chapter 2 investigates the effects of fungal colonization on maize's non-volatile defense responses, including specialized and primary metabolites as well as phytohormonal signaling pathways. High-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis revealed that benzoxazinoids (BXDs), the predominant class of maize secondary metabolites involved in plant defense, as well as the phenolic compound chlorogenic acid, were primarily induced by herbivory, with minimal alterations due to fungal colonization. A similar trend was observed for phytohormones, with herbivory acting as the primary driver of hormonal changes. However, untargeted metabolomic profiling using LC-QTOF-MS/MS system identified distinct metabolic shifts in fungal-inoculated seedlings, particularly those colonized by the wild-type strain. Feeding damage by herbivore further augmented these metabolic changes. Similarly, primary metabolites were differentially affected by fungal colonization and herbivore feeding. These findings provide insights into our earlier observations of H. armigera larval significantly attenuated performance in the wild- type fungal-colonized seedlings which reinforces the role of T. virens vir4 gene in differentially regulating certain metabolic features in maize that led to the enhanced resistance against this herbivore.
Chapter 3 is building on the findings from Chapter 2, which identified the T. virens vir4-derived sesquiterpene lactone heptelidic acid as a potential biomarker influencing fungal–plant–herbivore interactions and contributing to reduced herbivore performance. This chapter focuses on the extraction and purification of heptelidic acid and hydroheptelidic acid from wild-type T. virens and evaluates their larvicidal activity against H. armigera larvae. The results demonstrate that heptelidic acid significantly inhibited larval growth and exerted insecticidal effects at the tested concentrations. In contrast, hydroheptelidic acid exhibited limited larvicidal activity. These findings highlight the potential of T. virens-derived secondary metabolites as promising candidates for sustainable and eco-friendly pest management strategies targeting H. armigera.
Overall, this dissertation deepens our understanding of how T. virens influences maize defensive chemistry and its broader impact within a multitrophic system. The findings highlight fungus-induced plant resistance mediated primarily by T. virens vir4 biosynthetic gene and underscore the key role of this plant-microbe symbiotic relationship in enhancing plant resistance, vitaly important in the context of sustainable crop protection. Our study further highlights the potential of T. virens as a source of vital bioactive secondary metabolites that could play a critical role in sustainable pest management of H. armigera.2025-08-2
Pathological and genetic characterisation of JC Polyomavirus encephalopathy with an eleven-year-long disease course
No full textThe JCPy virus typically causes progressive multifocal leukoencephalopathy in immunocompromised humans and is characterised by multifocal demyelinated lesions of the white matter. In 2009, a case report described a JCPy virus infection with initial grey matter lesions and massive infection of cortical neurons, and named this disease JCPy virus encephalopathy. Genetic analysis revealed an archetype-like viral serotype, and a unique deletion in the Agno gene. No further publications with detailed histological descriptions are available.
We now investigated a patient with JCPy virus encephalopathy and an exceptionally long disease course over eleven years. We aimed at analysing the clinical symptoms, diagnostic findings, genetic features, and to provide a detailed neuropathological characterisation. To this end, formalin fixed, paraffin-embedded brain biopsy and autopsy tissue was used for triple immunohistochemical stainings. A staging system reflecting the lesional evolution was established and the viral infection and replication in neurons, different oligodendrocyte subpopulations and astrocytes was investigated. The cell loss of these populations was determined, as well as the acute and permanent axonal damage. Finally, the viral serotype (archetype versus prototype) was studied by quantitative polymerase chain reaction analysis.
Our patient developed myoclonia, seizures, and a global cognitive decline. Magnetic resonance imaging initially showed a cortical atrophy that progressed to a global atrophy and subcortical parenchymal lesions in later disease stages. No immunosuppressive condition was identified, except for a mutation of unclear significance in the interferon induced with helicase C domain 1 gene. JCPy virus encephalopathy was diagnosed by brain biopsy. Post-mortem brain tissue analysis revealed prominent grey-white junction lesions as a characteristic feature. These lesions showed an evolution form early stages with beginning demyelination to advanced stages with a dehiscence at the grey-white junction and pronounced cortical demyelination. Late lesion stages showed a demyelinated and atrophic cortical ribbon with neovascularisation and a cystic tissue defect of the underlying white matter. Tissue fragments of disconnected white matter “floating” in the cystic white matter cavity were named white matter islands. High numbers of infected and few virus replicating cells were found only in early grey-white junction lesions, that did not show any dehiscence yet. Neurons and astrocytes revealed an almost equally high infection rate, while numbers of infected oligodendrocytes were low, only peaking at the periphery of earliest lesions stages. Unclassifiable infected cells were found in limited numbers in the grey matter, and high numbers in the white matter. Few virus-replicating cells were present, and those that were identified were neurons. A minor neuronal cell loss was observed in early lesions, and a drastic loss in advanced lesions. Astrocytes also revealed a clear reduction only in late-stage lesions. In contrast, oligodendrocytes showed an early and subtotal loss in earliest lesion stages. White matter islands did not show a primary demyelination and oligodendrocytes were comparatively well preserved, however a pronounced axonal damage was found. Finally, genetic viral analysis revealed a prototype-like viral serotype that is typically found in the brain of progressive multifocal leukoencephalopathy patients.
Both the clinical symptoms as well as the cerebral imaging findings underline a cortical pathology, consistent with the diagnosis of JCPy virus encephalopathy. JCPy virus infections typically progress rapidly within weeks or months in immunosuppressed patients, so that the lack of a proven immunodeficiency and the extremely long disease course over 11 years are exceptional in our patient. Potentially, the mutation found in the interferon induced with helicase C domain 1 gene contributed to an immunodeficiency, as its protein initiates antiviral immune responses. Next to infected neurons, we identified grey-white junction lesions as the pathological hallmark of this disease. The long disease course allowed us to characterise the progression of the grey-white junction lesions and the resulting tissue damage. Results suggest that these dehiscent lesions are the most relevant pathomechanism leading to irreversible tissue damage. Why does this dehiscence occur in JCPy virus encephalopathy? Demyelination at the grey-white junction was associated with a pronounced axonal damage and numerous infected neurons in the lower cortical layers. We hypothesise that metabolic disturbances of infected neurons as well as the demyelination could lead to the pronounced axonal damage and tissue damage at the grey-white junction (“double hit”-theory).
Despite the prominent infection, most neurons, similar to astrocytes, survive the initial viral attack. Only single virus replicating neurons are present that may be involved in the spread of the virus. The pathomechanism leading to the massive neuronal infection remains unclear. While we could not confirm an archetype-like viral serotype, mutations in the Agno gene must further be analysed. In late lesion stages a pronounced neuronal loss is observed, now without evidence of viral infection. Axonal transections and the dehiscence may result in a retrograde neuronal degeneration. Also, due to a massive loss of afferent signals, an anterograde transneuronal degeneration may occur. Oligodendrocytes appear to play an important pathogenetic role not only in progressive multifocal leukoencephalopathy, but also in JCPy virus encephalopathy, as indicated by the subtotal loss that is observed already in earliest lesion stages. The pronounced cell loss and the high infection rate at the lesion periphery indicate that oligodendrocytes are a main viral target, causing a lytic infection and resulting in a massive cortical demyelination.
The present study is limited by the analysis of a single patient, due to the rarity of this disease entity. In vitro studies are warranted to explore the mechanisms of JCPy virus neuronal infections.
In conclusion, our histopathological analyses identify an initial cortical pathology with dehiscence at the grey-white junction and massive non-lytic infection of neurons as well as a lytic infection of oligodendrocytes as main pathology of JCPy virus encephalopathy. The resultant tissue damage includes a detachment of the grey and white matter with a pronounced neuronal loss and neovascularisation in the overlaying grey matter, and a severe tissue destruction in the underlying, non-demyelinated white matter.2025-12-1
Essays on the Economics of Global Food Security
No full textDiese Dissertation untersucht zentrale Herausforderungen bei der Verwirklichung gesunder und nachhaltiger Ernährungsweisen für Menschen weltweit, insbesondere in Ländern mit niedrigem und mittlerem Einkommen (LMICs). Im Fokus stehen die Rolle von Produktion, Märkten, Erschwinglichkeit und tief verwurzelten kulturellen Praktiken. In vier empirischen Essays kombiniere ich globale Datensätze, Haushaltsumfragen, anthropologische Quellen und Informationen zu Lebensmittelpreisen, um strukturelle, verhaltensbezogene und wirtschaftliche Einflussfaktoren auf Ernährungsvielfalt und -adäquatheit zu analysieren.
Essay 1 bewertet, inwieweit 186 Länder in der Lage sind, internationale Ernährungsempfehlungen
allein durch inländische Lebensmittelproduktion zu erfüllen. Unter Verwendung von Produktionsdaten für sieben Lebensmittelgruppen sowie Ernährungsempfehlungen der WWF Livewell-Diät zeigt die Analyse, dass über ein Drittel der Länder nur für keine, eine oder zwei Lebensmittelgruppen die Empfehlungen erfüllen kann. Viele kleine oder stark vom Handel abhängige Länder—insbesondere in der Karibik, Westafrika und im Golfraum—weisen eine geringe Selbstversorgung auf.
Essay 2 nutzt harmonisierte Daten zu Lebensmittelkonsum und -ausgaben von 1,1 Millionen Haushalten in 45 LMICs, um die Quellen der Ernährungsvielfalt zu untersuchen. Die Ergebnisse zeigen, dass Märkte die Hauptquelle für Nahrungsmittel darstellen—selbst für arme, ländliche und landwirtschaftlich orientierte Haushalte—insbesondere bei tierischen Produkten und Obst. Die Ernährungsvielfalt wird nahezu ausschließlich durch gekaufte Lebensmittel bestimmt, nicht durch Eigenproduktion. Zudem ist das Einkommen ein entscheidender Faktor für die Ernährung, wobei ärmere Haushalte sich nährstoffreiche Lebensmittel oft nicht leisten können.
Essay 3 untersucht die langfristige Persistenz kultureller Einflüsse auf den Lebensmittelkonsum, indem anthropologische Daten zu traditionellen Viehhaltungssystemen mit Haushaltsdaten verknüpft werden. Mittels Regression-Discontinuity-Designs und ethnisch verknüpfter Daten zeigt sich, dass Haushalte in Regionen mit historischer Rinderhaltung heute mehr tierische Produkte (ausgenommen Rindfleisch), Milch, und Gemüse konsumieren. Diese Muster bleiben auch bei Kontrolle sozioökonomischer und geographischer Faktoren bestehen, was auf eine intergenerationelle Weitergabe von Ernährungsvorlieben und Viehhaltungstraditionen hinweist.
Essay 4 führt neue globale Armutsgrenzen ein, die auf der Erschwinglichkeit von gesunden
Mindestkosten-Ernährungsweisen basieren. Diese „Healthy Diet Poverty Lines“ (HPLs) fassen
Armut als das Unvermögen auf, sich eine ernährungsphysiologisch angemessene Ernährung zu
leisten—nicht nur eine kalorisch ausreichende. Laut dieser Schwellenwerte lebten 2022 weltweit
zwischen 2,3 und 2,9 Milliarden Menschen in Armut—das ist 3,5- bis 4,4-mal so viel wie nach
der konventionellen Armutsgrenze von 2,15 US-Dollar pro Tag. Die globale Einkommenslücke
zur Deckung gesunder Ernährung beläuft sich auf 1,7 bis 2,4 Billionen US-Dollar jährlich.This dissertation investigates key challenges in achieving healthy and sustainable diets for people around the globe, in low- and middle-income countries (LMICs) in particular. It focuses on the roles of production, markets, affordability, and deep-rooted cultural practices. Across four empirical essays, I combine global datasets, household survey data, anthropological records, and food price information to explore the structural, behavioral, and economic determinants of
diet diversity and adequacy.
Essay 1 evaluates the capacity of 186 countries to meet international dietary guidelines through domestic food production alone. Using adjusted production data across seven food groups and dietary benchmarks from the WWF’s Livewell diet and EAT-Lancet recommendations, the analysis reveals that over one-third of countries can meet recommendations for only zero, one, or two food groups. Many small or trade-dependent countries—particularly in the Caribbean, West Africa, and the Gulf—lack production self-sufficiency, with little improvement projected through 2032.
Essay 2 uses harmonized food consumption and expenditure data from 1.1 million households across 45 LMICs to examine the sources of dietary diversity. Results show that markets are the dominant source of food—even for poor, rural, and agricultural households—particularly for animal-source foods and fruits. Diversity in diets is driven almost entirely by purchased
foods rather than own production. Moreover, poor households often cannot afford nutrient-rich foods.
Essay 3 explores the long-term persistence of cultural traits on food consumption by linking anthropological records of ancestral livestock practices with household-level diet data. Using a regression discontinuity design and ethnicity-linked data, the analysis finds that households in historically cattle-reliant societies exhibit higher consumption of animal-source foods (excluding beef), milk, vegetables, and higher dietary diversity today—despite cattle traditionally being less used for subsistence. These patterns persist even after accounting for socioeconomic and geographic factors, pointing to intergenerational transmission of food preferences and livestock practices.
Essay 4 introduces new global poverty lines based on the affordability of least-cost healthy diets. These Healthy Diet Poverty Lines (HPLs) redefine poverty to include nutritious diets, not just caloric sufficiency. Applying these thresholds suggests that between 2.3 and 2.9 billion people globally are poor—3.5 to 4.4 times more than those identified using the conventional \2.4 trillion annually.2025-09-1