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Retrospektive Mortalitätsanalyse geriatrischer unfallchirurgisch-orthopädischer Patienten der Universitätsmedizin Göttingen zwischen 2013 und 2017
No full textDue to demographic change, the number of older patients in trauma surgery and orthopedics is steadily increasing. Comorbidities and age-related changes such as reduced physical and mental adaptability in geriatric patients make their treatment very complex and mortality high. In recent years, there has therefore been increased research into interdisciplinary treatment of older patients and possible approaches to reducing mortality. However, critical time intervals with an increased risk of in-hospital mortality after the acute phase have not yet been established. Since knowledge about this and about the factors influencing mortality is essential for a possible reduction in in-hospital mortality in older patients, this study was conducted.
This study is a retrospective study conducted at the University Medical Center Göttingen, in which data from 6,201 trauma surgery and orthopedic patients over the age of 60 from 2013 to 2017 were collected and analyzed. The aim was to analyze in-hospital mortality and investigate factors influencing mortality. In addition, a critical in-hospital time interval with an increased risk of mortality after the acute phase was defined and evaluated.
Overall, this study found an in-hospital mortality rate of 2.7%. In the statistical analysis, the parameters treatment method, age, presence of a resistant pathogen, day of discharge, and discharge ward showed a significant influence on mortality. The in-hospital mortality rate did not differ significantly between treatment methods (surgery: 2.8%; conservative therapy: 2.5%), while the other significant parameters had a clear influence on mortality in some cases. The in-hospital mortality rate increased with age (60-69 years: 1.3%; over 80 years: 4.7%). The presence of a resistant pathogen also significantly reduced the survival rate according to the data collected in this study. With regard to the day of discharge, more patients died on a weekend or public holiday than on a weekday, regardless of the treatment method. The different discharge wards represented a special feature in this study, so that the focus was placed on the normal ward with regard to in-hospital mortality. The in-hospital mortality rate in the normal ward was 0.6% for the entire patient population (operated patients: 0.5%; conservatively treated patients: 0.8%). The parameters “gender,” “type of admission,” and “day of admission” had no statistically significant influence on mortality.
The results of this study show that there appears to be a critical time interval after the acute phase with an increased risk of mortality for geriatric trauma surgery and orthopedic patients. In this study, this was determined for the entire patient population from day 10 to day 21. For the group of patients who underwent surgery, a critical time interval from day 13 to day 26 was identified, and for patients treated conservatively, from day 4 to day 13. Further studies are needed to examine the influence of other parameters on the critical time interval, as the patient population sizes of deceased patients were too small for more in-depth analyses.2025-09-1
Reductive Elimination in Transition Metal Complexes: Selectivity and Trends across the d-Block
No full textTransition metal-catalyzed cross-coupling chemistry requires more insights into the details of
diverse and complex reaction mechanisms of different metals and the factors influencing them.
This thesis aimed to investigate the reductive elimination step of a broad range of transition
metals by applying electrospray ionization mass spectrometry as an established method to
investigate short lived organometallic species.
Homoleptic gas phase metalate species were generated by transmetalation of methyl, phenyl,
(trimethylsilyl)methyl and mesityl groups onto transition metal precursors and electrospray
ionization of the resulting reaction mixtures. They were then fragmented with collision induced
dissociation to study their intrinsic unimolecular reactivity. The selectivity between reductive
elimination and radical loss in homoleptic metalates [M(TMSM)4]− of the first-row transition
metals was found to be governed by the threshold of the first radical loss step. This threshold
increased from manganese to copper, causing a switch from predominant one-electron radical
dissociation for manganese to nickel to two-electron reductive elimination for copper.
Gas phase species containing four aryl groups generated from transmetalation of aryl reagents
to cobalt(II) salts were found to likely possess the structure [Co(Ar)2(η-Ar2)]− instead of
[Co(Ar)4]−, as they were assigned in earlier works.
Lithium-bridged metalates species with mixed coinage metal centers [LiMM'(Me)8]− with
M, M' = Cu, Ag, Au were generated and the relative reaction rates of Cu>Ag>Au in the
reductive elimination were directly investigated from the fragment distribution of the post-
reductive elimination species [LiMM'(Me)6]−. The first reductive elimination step proceeded
exclusively on the more reactive metal center in each case. Analogous lithium-bridged species
could not be generated for combinations of iron, cobalt, and nickel.
Electronic and steric substituent effects on the reductive elimination step were investigated in
tetraorganyl aurates. A linear free energy correlation was found for the electronic influences
on para-substituded aryl aurates with a reaction parameter of ρ = −0.34 (0.29). Measurements
with ortho-alky substituted aryl aurates revealed preferred elimination of less sterically
hindered groups, indicating that the approach of the coupling partners was the defining factor
for the observed selectivity. Mixed alkyl aurates together with H and benzyl groups gave no
clear correlations as to the governing factors between electronic and steric influences of the
ligands.2025-08-2
Size sensitive rheology of reconstituted actin and vimentin filament networks
No full textIntermediate filament (IF) networks provide mechanical resilience to cells. Understanding their viscoelastic properties—and crucially, their dependence on the length scale of deformation—is vital for deciphering physiological function. This study investigates the scale-dependent mechanics of vimentin IF networks across linear and nonlinear regimes, systematically contrasting them with actin networks, which are primarily responsible for facilitating cell movement.
We integrate single-point (1P) and two-point (2P) passive microrheology with optical-tweezers-based microrheology (both passive and active) to systematically dissect size-dependent mechanics in in vitro protein networks. A new automated approach is developed to characterize probes on different length scales simultaneously and quantify the magnitude of these changes with regard to their statistical significance. A significant resulting contribution is that while employing polydisperse probes within identical samples, eliminating artifacts from sample preparation and enabling direct comparison of local versus bulk dynamics also using different-sized particle pair correlations. The shear modulus plateaus were shown to be dependent when probe size exceeds the network mesh size, as demonstrated in vimentin and confirmed in actin. This confirms that observed size effects reflect intrinsic network physics. Mesh sizes were also quantified for both systems. The work further establishes the scope of strain-relaxation dynamics measurements in pure vimentin. Due to its complex viscoelasticity, active-passive calibration was implemented prior. To probe network properties by separate means, we also introduced fluorescently labeled filaments and extracted key filament characteristics via imaging for quantitative model comparison.
Actin networks was shown to be conforming to semiflexible polymer theory. Vimentin, however, displays unique complexity—its linear mechanics fit semiflexible predictions, but its nonlinear viscoelasticity necessitates empirical models (such as fractional Kelvin-Voigt). This reflects vimentin’s broader relaxation spectrum and molecular intricacies, potentially involving load-induced structural transitions. Critically, a strain-rate-dependent crossover in force relaxation was observed: deformations exceeding characteristic network timescales shift responses from exponential to power-law decay, possibly linking filament reorganization to emergent nonlinearity.2025-09-0
The role of Sec61β in Ebola and Marburg virus glycoprotein processing and the potential of the Sec61 channel as antiviral target
No full textEbola-Virus (EBOV) und Marburg-Virus (MARV) gehören zu Familie der Filoviridae. Sie sind für Menschen und nichtmenschliche Primaten (NHP) hochgradig pathogen und führen vor allem in West-, Ost- und Zentralafrika zu wiederkehrenden Ausbrüchen. Zugelassene Impfstoffe gibt es nur für eine von den fünf Filovirus-Spezies, die nachweislich Menschen infizieren können. Die Behandlungsmöglichkeiten sind sehr begrenzt und beruhen hauptsächlich auf unterstützenden Maßnahmen. Antivirale Medikamente gegen Filoviren werden daher dringend benötigt. Die Adressierung von Wirtszellproteinen durch antivirale Medikamente wurde als vielversprechende Strategie zur Entwicklung potenzieller Breitbandmedikamente mit geringerer Resistenzneigung beschrieben. Studien mit Flaviviren deuteten darauf hin, dass sich Proteine des ER-Importweges dafür eignen könnten. So sind einerseits sind behüllte Viren von der Translokation ihres Glykoproteins (GP) durch den Sec61-Kanal als Teil des ER-Importweges abhängig und andererseits ist der Verlust dieser ER-Proteine mit dem zellulären Überleben vereinbar.
Auf dieser Grundlage habe ich die Auswirkungen von Sec61β, einer kleinen Untereinheit des Sec61-Translokationskanals, auf die Prozessierung und Funktion von Filovirus-Glykoproteinen untersucht. Dazu habe ich SEC61B-KO-Zellen generiert. Ich konnte zeigen, dass der Verlust von Sec61β deutlich die proteolytische Spaltung von MARV-GP, aber nicht von EBOV-GP verhinderte. Darüber hinaus konnte ich zeigen, dass die Spaltung von MARV-GP an einer Furinschnittstelle (FCS), die sich zwischen den GP-Untereinheiten GP1 und GP2 befindet, für den Zelleintritt von Pseudoviren, die MARV-GP tragen, wichtig ist. Das unterscheidet sich von bereits veröffentlichten Arbeiten zu EBOV, die zeigen, dass die FCS für den viralen Eintritt verzichtbar ist. Meine Analyse mehrerer anderer Mitglieder der Filoviridae-Familie zeigt, dass die FCS für alle getesteten Ebolavirus GPs und das Lloviu-Virus GP entbehrlich ist, während eine defekte FCS verringerten Eintritt aller getesteten Marburgvirus GPs vermittelt, auch wenn stamm- und zelltypspezifische Unterschiede beobachtet wurden. Darüber hinaus konnte ich nachweisen, dass SKI-1, welches wie Furin ein Mitglied der Proprotein-Konvertasen ist, MARV-GP spalten kann. Meine Ergebnisse lassen vermuten, dass der Defekt der MARV-GP-Spaltung in SEC61B-KO-Zellen auf eine verminderte Proprotein-Konvertase-Aktivität und/oder auf eine veränderte N-Glykosylierung von GP zurückzuführen sein könnte. Abschließend konnte ich gemeinsam mit Partnern zeigen, dass die Inhibition des Sec61-Kanals durch Apratoxin S4 die Infektion mit EBOV und MARV blockiert.
Zusammengefasst konnte ich zeigen, dass der Sec61-Kanal als Teil des ER-Translokationskomplexes ein vielversprechendes Ziel in Wirtszellen bei Filovirus-Infektionen darstellt.Ebola virus (EBOV) and Marburg virus (MARV), members of the family of Filoviridae, are highly pathogenic for humans and non-human primates (NHPs) and lead to reoccurring outbreaks mainly in the region of West, East and Central Africa. Licensed vaccines exists only for one out of five filovirus species, which have been shown to infect humans. Treatment options are very limited and rely mostly on supportive care. Thus, antiviral drugs against filoviruses are urgently needed. Targeting host cell proteins is a promising strategy to enable broad-spectrum antiviral activity and to reduce resistance development. Previous studies on flaviviruses indicated that proteins of the ER import pathway might constitute suitable targets. On the one hand enveloped viruses depend on translocation of their glycoprotein (GP) through the Sec61 channel as part of the ER import pathway and on the other hand knockdown of these ER proteins showed to be compatible with cellular survival.
Based on this, I studied the impact of Sec61β, a small subunit of the Sec61 translocation channel, on filovirus glycoprotein processing and function. For this, I generated SEC61B-KO cells. I demonstrated that loss of Sec61β markedly reduced proteolytic processing of MARV-GP, but not EBOV-GP. Furthermore, I could show that cleavage of MARV-GP at a furin cleavage site (FCS) located between the GP subunits GP1 and GP2 is important for cell entry of pseudoviruses bearing MARV-GP, which is distinct to published work on EBOV, showing that the FCS is dispensable for viral entry. My analysis of several other members of the Filoviridae family showed that the FCS was dispensable for all Ebolavirus GPs tested and Lloviu virus GP whereas a defective FCS reduced entry driven by all Marburgvirus GPs tested, although strain and cell type specific differences were observed. In addition, I provided evidence that SKI-1, like furin a member of the proprotein convertases, can cleave MARV-GP. My results suggest that the defect in MARV-GP cleavage in SEC61B-KO cells might be due to reduced proprotein convertase activity and/or altered N-glycosylation of GP. Finally, I could show jointly with partners that inhibition of the Sec61 channel by Apratoxin S4 blocks EBOV and MARV infection.
Taken together, I demonstrated that the Sec61 channel, as part of the ER translocation complex, is a promising host cell target for filovirus infections.2025-11-1
Auswirkungen der COVID-19-Pandemie auf psychiatrische Störungen: Ein Vergleich von Autismus-Spektrum-Störungen und depressiv Erkrankten anhand der COVID-Studie
No full textThe COVID-19 pandemic substantially increased psychosocial stress, yet little is known about its effects on individuals with pre-existing psychiatric disorders. This dissertation compared patients with depression (n=41) and autism spectrum disorder (ASD; n=15) using data from the COVID study at the University Medical Center Göttingen. Standardized interviews assessed psychosocial burden (GoPSI), adjustment disorder (ADNM-20), and resilience before the pandemic, during the first lockdown, and during the second lockdown. Both groups showed significantly higher burden and lower resilience in the first lockdown, with partial improvements thereafter. Quantitative outcomes did not differ significantly, but qualitative reports highlighted distinct challenges: loneliness in depression and disrupted routines in ASD.2025-10-2
Transferable Building Blocks for Rapid & Accurate Prediction of Proteins and Molecular Crystals Optoelectronic Properties
No full textPropriedades eletrostáticas, como momentos de dipolo, polarizabilidade e índice de
refração, são essenciais para compreender interações moleculares, estabilidade e reatividade,
particularmente em proteínas. Essas propriedades influenciam a estrutura, função e
comportamento de tais moléculas em sistemas biológicos, permitindo o design destas com
características elétricas personalizadas para aplicações, por exemplo, em biocatálise. No
entanto, calcular essas propriedades para macromoléculas utilizando métodos quânticos é
computacionalmente caro. Para superar isso, utiliza-se a transferibilidade da densidade
eletrônica de sistemas semelhantes, analisando grandes moléculas em termos de blocos
construtores menores, como átomos ou grupos funcionais. O banco de dados desenvolvido,
GruPol, é capaz de estimar os momentos de dipolo e polarizabilidades de proteínas utilizando
a metodologia de transferibilidade de blocos construtores entre sistemas similares.
Ainda, incorporam-se efeitos de polarização através de um Modelo de Interação de Dipolos
que considera interações com solventes e mudanças de pH. Além disso, o CrysPol, uma
ferramenta complementar, prevê índices de refração e polarizabilidades de cristais moleculares,
permitindo estimar tais propriedades e suas dependências de frequência do campo
externo.Electrostatic properties such as dipole moments, polarizability, and refractive index
are essential for understanding molecular interactions, stability, and reactivity, particularly
in proteins. These properties influence the structure, function, and behavior of such a
molecules in biological systems, enabling the design of proteins with customized electrical
characteristics for applications, for example, in biocatalysis and drug delivery. However,
calculating these properties for large macromolecules using quantum methods is computationally
demanding. To overcome this, electron density transferability from similar systems
is employed, analyzing large molecules in terms of smaller building blocks, such as atoms
or functional groups. GruPol, a software tool developed here, predicts the dipole moments
and polarizabilities of proteins using a database of functional group properties. Moreover,
a Dipole Interaction Model is employed to consider solvent interactions and pH changes.
Additionally, CrysPol, a companion tool, predicts refractive indices and polarizabilities of
molecular crystals, enabling the prediction of frequency-dependent properties. These tools
offer valuable insights into protein interactions and support the rational design of proteins
and materials with tailored electrostatic properties.2025-09-2
Predictive Factors for the Need of Tracheostomy in Patients With Large Vessel Occlusion Stroke Being Treated With Mechanical Thrombectomy
No full textHintergrund: Patienten mit einem ischämischen Schlaganfall infolge eines Verschlusses großer Hirngefäße (LVOS), die sich einer mechanischen Thrombektomie (MT) unterziehen, sind sowohl für schlaganfallbedingte als auch nicht-schlaganfallbedingte Komplikationen anfällig, die eine Tracheotomie (TS) erforderlich machen können. Risikofaktoren für die Durchführung einer TS wurden in dieser spezifischen Patientengruppe bislang nicht systematisch untersucht.
Methodik: In dieser monozentrischen, retrospektiven Analyse wurden prospektiv erhobene Daten von LVOS-Patienten ausgewertet, die zwischen 2014 und 2019 nach MT auf einer neurologischen Intensivstation eines akademischen Zentrums behandelt wurden. Mittels logistischer Regressionsanalysen wurde der prädiktive Wert peri- und postinterventioneller Variablen, bildgebender Befunde sowie der prämorbiden Anamnese in Bezug auf die Indikation zur Tracheotomie während des Intensivaufenthalts untersucht.
Ergebnisse: Von insgesamt 635 Patienten, die eine MT erhielten, wurden 40 (6,3 %) im Verlauf ihres Aufenthalts auf der Neuro-Intensivstation tracheotomiert. Diese Patienten waren im Median jünger [71 (62–75) vs. 77 (66–83) Jahre, p < 0,001], wiesen initial höhere NIHSS-Werte auf [18 (15–20) vs. 15 (10–19), p = 0,009] und zeigten signifikant erhöhte Raten an nosokomialer Pneumonie (HAP) [97,5 % vs. 37,6 %, p < 0,001], fehlgeschlagenen Extubationen [37,5 % vs. 3,2 %, p < 0,001], Sepsis [27,5 % vs. 2,7 %, p < 0,001], symptomatischer intrazerebraler Blutung [12,5 % vs. 3,9 %, p = 0,026] sowie dekompressiver Hemikraniektomie (DH) [51,4 % vs. 3,8 %, p < 0,001].
In der multivariaten Regressionsanalyse blieben HAP (OR 21,26; 95 %-KI 2,76–163,56; p = 0,003), Sepsis (OR 5,39; 95 %-KI 1,71–16,91; p = 0,004), fehlgeschlagene Extubationen (OR 8,41; 95 %-KI 3,09–22,93; p < 0,001) sowie DH (OR 9,94; 95 %-KI 3,92–25,21; p < 0,001) als unabhängige Prädiktoren für die Notwendigkeit einer TS bestehen.
Ein längerer Zeitraum zwischen Aufnahme und TS korrelierte mit einer verlängerten Verweildauer auf der Intensivstation (r = 0,384; p = 0,03), zeigte jedoch keinen signifikanten Zusammenhang mit dem funktionellen Outcome (NIHSS bei Entlassung: r = 0,125; p = 0,461; modifizierte Rankin-Skala nach 90 Tagen: r = –0,179; p = 0,403).
Schlussfolgerung: Bei LVOS-Patienten, die sich einer MT unterziehen, besteht ein erhöhtes Risiko für eine Tracheotomie insbesondere bei fehlgeschlagenen Extubationen, nach Durchführung einer DH sowie bei Auftreten schwerer infektiöser Komplikationen in der Akutphase. Diese Parameter können entscheidend zur Indikationsstellung und zum Timing einer TS beitragen und könnten helfen, die Sedierungsdauer zu reduzieren sowie die Verweildauer auf der Intensivstation zu verkürzen.Background: Patients with large vessel occlusion stroke (LVOS) who are eligible for mechanical thrombectomy (MT) are at risk for both stroke-related and non-stroke-related complications that may necessitate tracheostomy (TS). Risk factors for TS have not yet been systematically investigated in this specific subgroup of stroke patients.
Methods: This single-center study analyzed prospectively collected data from patients with LVOS treated with MT between 2014 and 2019 in a large academic neurological intensive care unit (neuro-ICU). The predictive value of peri- and post-interventional factors, stroke imaging findings, and pre-stroke medical history was assessed using logistic regression models to determine their potential in predicting tracheostomy during the ICU stay.
Results: Among 635 LVOS patients treated with MT, 40 (6.3%) underwent tracheostomy during their neuro-ICU stay. Patients who required TS were younger [71 (62–75) vs. 77 (66–83) years, p < 0.001], had higher initial National Institutes of Health Stroke Scale (NIHSS) scores [18 (15–20) vs. 15 (10–19), p = 0.009], and showed higher rates of hospital-acquired pneumonia (HAP) [39 (97.5%) vs. 224 (37.6%), p < 0.001], failed extubation [15 (37.5%) vs. 19 (3.2%), p < 0.001], sepsis [11 (27.5%) vs. 16 (2.7%), p < 0.001], symptomatic intracerebral hemorrhage [5 (12.5%) vs. 22 (3.9%), p = 0.026], and decompressive hemicraniectomy (DH) [19 (51.4%) vs. 21 (3.8%), p < 0.001].
In multivariable logistic regression analysis, HAP [odds ratio (OR) 21.26, 95% confidence interval (CI) 2.76–163.56, p = 0.003], sepsis [OR 5.39, CI 1.71–16.91, p = 0.004], failed extubation [OR 8.41, CI 3.09–22.93, p < 0.001], and DH [OR 9.94, CI 3.92–25.21, p < 0.001] remained the strongest predictors for TS.
Patients with longer intervals between admission and TS had prolonged ICU stays (r = 0.384, p = 0.03). However, there was no correlation between the timing of TS and clinical outcome (NIHSS at discharge: r = 0.125, p = 0.461; modified Rankin Scale at 90 days: r = -0.179, p = 0.403).
Conclusions: Patients with LVOS undergoing MT are at elevated risk of requiring TS, particularly when extubation fails, DH is necessary, or severe infectious complications occur during the acute phase of ischemic stroke. These factors likely inform both the indication and optimal timing of tracheostomy, with the potential to reduce overall sedation and shorten ICU length of stay.2025-11-2
Enantioselective C–H Activations via Cobalt-/Nickel- Electrocatalysis and Iron-Catalyzed C–H Alkylations
No full textDuring the past decade, catalytic C–H activation strategies with transition metal catalysts have been established. However, achieving more sustainable enantioselective transformations with cost-effective base metal catalysts remained
challenging. To address this limitation, in this thesis, novel enantioselective C–H activation strategies based on cobalt, nickel, and iron catalysis were developed. Moreover, in the devised cobalt- and nickel catalytic systems, electrochemistry could
be utilized as an abundant oxidant surrogate to allow efficient catalysis. In addition, the sustainable energy carrier molecular hydrogen (H2) was generated as an attractive byproduct. In the first project, an enantioselective cobaltaelectro-catalyzed annulation of aryl hydrazones with olefins was achieved, furnishing valuable, Fsp³-rich indanes
181 (Scheme 4.1). Moreover, the previously unprecedented potential of novel chiral κ²-N,O-oxazoline enols and amide preligands for enantioselective C–H activation could be demonstrated. Based on these findings, novel chiral κ²-N,O-oxazoline urea and thiourea ligands were designed and synthesized. Thereby challenging enantioselective cobaltaelectrocatalyzed
C–H annulations furnished indoles 183 with multiple distinct chiral C–N axes (Scheme 4.2).This electrocatalytic approach is exceptionally mild, straightforward to operate, and generates only molecular hydrogen (H2) as the sole stoichiometric byproduct. With these results, the foundations for the utilization of κ²-N,O-oxazoline urea ligands in enantioselective catalysis are set. Based on the presented data, we anticipate that the devised chiral κ²-N,O-oxazoline preligands provide a valuable contribution to the known chiral ligand toolbox and expect their utilization in enantioselective catalysis in the future. Afterwards, enantioselective cobaltaelectro-catalyzed C–H activations beyond traditional C–H/N–H annulations were explored. More specifically, the robustness of a traceless carboacylation of benzamides 33 with bridged 7-oxabenzonorbornadienes
45 was described (Scheme 4.3). Notably, during this transformation, four stereogenic centers were generated simultaneously. In contrast, nickelaelectro-catalysis was found to be also viable, but furnished the corresponding dihydroisoquinolinones 262. In this case, a data-driven approach guided the discovery of previously unknown chiral Salox ligand derivatives which was essential to achieve high enantioselectivity during catalysis. Moreover, the devised strategy represents the first example of an
enantioselective nickelaelectro-catalyzed C–H activation. In the last part of this thesis, the versatility, robustness and product diversification of the first atropo-enantioselective iron-catalyzed C–H alkylation of indoles 187 was
showcased (Scheme 4.4). Here, the presence of the chiral NHC ligand L42 with the dispersion energy donor (DED) motifs was essential to achieve high reactivity and selectivity. Noteworthily, during catalysis, C–N axial as well as C-central chirality was successfully induced simultaneously. The desired C(2)-alkylated indole products 188 could be
obtained in excellent yields, diastereo- and enantioselectivities.2025-11-1
New entrants and holistic business models in agriculture
No full textAgriculture is becoming increasingly heterogeneous in its structure and output, accompanied by multifaceted expectations for the future, which adds complexity to political frameworks and support schemes. Addressing these developments requires innovative transitional processes and solutions. Associated with this, new evaluation concepts are required to capture and aggregate the individual and qualitative contributions of supported enterprises, especially concerning public, social, and ecosystem services. From a bottom-up perspective, the systematic analysis and presentation of new production methods can facilitate the upscaling of innovative solutions and practices.
To support green and social transitions in agriculture, solutions from novel areas in the sector should be investigated. Although specific aspects of these novel areas have been partly explored, systematic investigations are lacking. Considering entry methods into farming, comparing traditional farm successors with the category of newcomers from outside the sector, can strengthen support for new entrants. Newcomers often enter agriculture by implementing innovative business models. A holistic template for investigating these business models is beneficial for capturing and transferring their multifunctional contributions.
This dissertation addresses two key aspects: new entrants and business models. First, it analyses the differences between two groups of new entrants—family successors and newcomers—because they are pivotal for generational renewal and sustainable business transformations. Second, it seeks to holistically capture innovative business models to derive transfer-able implications for the broader implementation of nature-based solutions (NBS), including novel production systems (e.g., urban agriculture, indoor farming, and aquaponics) and production methods.
The following research questions are addressed:
I. Is an individual consideration of the two new entrant groups beneficial in relation to their individual contributions and necessary regarding each group´ requirements (Contribution 1)?
II. What conceptual framework enables the holistic capture of NBS business models (Contribution 2)?
III. Which transferable governance and financing concepts exist within NBS business model clusters (Contribution 3)?
Methodologically, a quantitative online survey of new entrants across several European countries was used to test five hypotheses derived from the literature. A regression model was employed to determine whether differentiating between the two groups of new entrant farmers is necessary (Contribution 1). Guided interviews based on a new business model template derived from the literature were conducted on NBS implementations in different countries. Pestoff’s welfare triangle was applied to cluster NBS interventions into business model clusters to develop transferable implications (Contributions 2 and 3).
The results showed that compared with established farmers, new entrants are more likely to innovate in agriculture. For the respective sample, the regression model determined type-dependent differences between family successors and newcomers. Newcomers bring ideas, innovations, and networks to the agricultural sector and rural areas, where most of their work and living activities take place. Even after entering agriculture, their reliance on limited production resources fosters innovative resource-efficient solutions and sustainable transformations (Contribution 1).
To fully understand these business models, a holistic analysis is required. The Nature-based Sustainability Business Model Canvas (NB S BMC) considers not only economic but also societal and ecological dimensions, providing a general tool for capturing and evaluating innovative business models on a valid and comparable basis (Contribution 2). Clustering heter-ogeneous business models allows for the derivation of transferable implications. By applying Pestoff’s welfare triangle to the NBS case study, three business model clusters emerge: public provisions, sales, and diversification. NBS governance models are highly adaptable, independent of business model type, and can include a diverse range of stakeholders. Given the temporary nature of public support, alternative financing strategies, such as donation models, collaborations with research and commerce, and recurring revenue streams, are crucial for the sustainability of public and diversified business model clusters (Contribution 3).
In conclusion, this cumulative dissertation highlights the need for the systematic investigation of novel agricultural approaches. New entrants and NBS contribute considerably to innovative transition processes and solutions. Their contributions and requirements must be considered by using individual approaches. Owing to their heterogeneous and multifaceted achievements, the business models of newcomers and NBS can only be effectively captured using holistic concepts. Financing remains a common challenge in these novel areas owing to their early stages and limited resources. Therefore, tailored support schemes are required to achieve targeted upscaling.
The areas examined in this dissertation qualitatively contribute to economic, social, and ecological innovation. Further research is required to explore the scalability of newcomers’ and NBS` qualitative contributions and their potential to contribute quantitatively to overall agricultural production.2025-12-0
Die Entwicklung und der Verlauf der REM-Schlaf-Verhaltensstörung bei Parkinson-Patienten
No full textREM sleep behaviour disorder (RBD) is a parasomnia that occurs predominantly in neurodegenerative diseases such as Parkinson’s disease (PD). Moreover, in individuals with an established diagnosis of PD, RBD is associated with a more severe disease progression. However, only few studies assess the individual evolution of REM sleep without atonia (RWA) in PD patients. The 'de Novo Parkinson' study examines the longitudinal progression of RBD in a cohort of 159 de novo PD patients. RBD prevalence increased from 25% at baseline to 52% after six years. Among 31 patients with valid serial video-polysomnographies, the share of RWA increased significantly (p< 0.001) from 19% to 41% modeled to grow by 29.7% every two years. Age (p<0.04) and time (p<0.001) were identified as independent factors influencing RWA significantly. Sex, LEDD, UPDRS sum scores, benzodiazepines, MMSE total scores and dyskinesia showed no significant effect. The results support the role of RBD and RWA as progression markers in Parkinson’s disease and confirm the need for further research into its determinants and clinical implications.2026-01-1