Ausgewählte Chancen und Herausforderungen der digitalen Transformation für die Produktentwicklung und Unternehmensorganisation im Finanzdienstleistungssektor

Vor dem Hintergrund der digitalen Transformation sind Finanzdienstleistungsunternehmen auf unterschiedlichen Ebenen zahlreichen Chancen sowie Herausforderungen ausgesetzt. Während der Einsatz neuer Technologien die Optimierung bestehender Geschäftsprozesse sowie das Angebot digitalisierter Finanzdienstleistungen ermöglicht, geht dies zugleich mit veränderten Arbeitsbedingungen innerhalb der Unternehmensorganisation einher. Darüber hinaus sind Finanzdienstleister dazu angehalten die sich ändernden Kundenerwartungen bei den bisherigen Geschäftsaktivitäten sowie bei der Produktentwicklung zu berücksichtigen. Das Ziel der vorliegenden kumulativen Dissertation ist es, bestehende Forschungsdesiderate hinsichtlich der Auswirkungen der digitalen Transformation auf den Finanzdienstleistungssektor, differenziert nach der Kunden- und Produktperspektive sowie der internen Unternehmensperspektive, vertiefend zu analysieren. Das Technology-Organization-Environment (TOE)-Framework von DePietro et al. (1990) wird dabei als theoretischer Rahmen zur Einordnung und Strukturierung der Forschungsmodule verwendet. Die Ergebnisse der acht Module zeigen, dass die Kundenbedürfnisse und –erwartungen im Finanzdienstleistungssektor verstärkt von der digitalen Transformation beeinflusst werden. Dies zeigt sich in der Beratungstätigkeit bspw. durch das Angebot neuer Kundenkanäle sowie der aus dem steigenden Wettbewerbsdruck resultierenden erhöhten Preistransparenz. Im Rahmen der Produktentwicklung sind zudem u. a. ESG-Risiken und Silent Cyber-Risiken zu beachten. Aus der Analyse der Auswirkungen der digitalen Transformation auf die Unternehmensorganisation geht hervor, dass über den Einsatz digitaler Innovationen innerhalb des Backoffice die Realisation von Effizienzgewinnen sowie das Entgegenwirken eines Personalmangels möglich ist. Darüber hinaus wird in den Modulen der Einfluss des Faktors Mensch auf die Cyber-Sicherheit hervorgehoben. Während dieser einerseits als „schwächstes Glied“ und potenzielles Angriffsziel im Sicherheitskonstrukt der Unternehmen dargestellt wird, ist andererseits das Potenzial der Beschäftigten zur Frühwarnung zu berücksichtigen

Die proximale Humerusfraktur: ist die Operation immer die beste Wahl

Hintergrund Proximale Humerusfrakturen gehören zu den dritthäufigsten, osteoporotischen Verletzungen mit steigender Inzidenz. Die Indikationsstellung wird weiterhin kontrovers diskutiert. Ziel unserer Studie war es herauszufinden, ob der Trend zur konservativen Therapie gerechtfertigt ist und sich hiermit v. a. beim geriatrischen Patienten vergleichbare, reproduzierbare Ergebnisse erreichen lassen. Material und Methoden In die retrospektive Single-center-Studie wurden 128 Patienten mit konservativer und kopferhaltender operativer Therapie zwischen 2013 und 2015 eingeschlossen und davon wurden 91 nachuntersucht. Demografische Daten, operative Versorgung sowie Komplikationen wurden erhoben. Eine Follow-up-Untersuchung fand statt, in der Subjective Shoulder Value (SSV), visuelle Analogskala (VAS), Disability of Arm, Shoulder and Hand Questionnaire (DASH), Constant Murley Score (CMS) und Bewegungsausmaß erhoben wurden. Eine radiologische Auswertung wurde durchgeführt. Ergebnisse In den Scores wurden folgende Ergebnisse für konservative und operative Therapie erzielt (konservativ: VAS Schmerz 8,9 Punkte, CMS abs. 70,7 Punkte, DASH: 16,5 Punkte; operativ: VAS Schmerz 1,7 Punkte, CMS abs. 63,5 Punkte, DASH: 24,2 Punkte). Es zeigte sich kein signifikanter Unterschied zwischen Nagel- und Plattenosteosynthese. Die Komplikationsrate betrug 20 %. Die konservative Gruppe erzielte ein besseres Bewegungsausmaß. Die dislozierten Frakturen waren auffallend, wenngleich nicht statistisch signifikant schlechter im Vergleich zu den Neer-1-Frakturen und nur leichtgradig schlechter als die operativ versorgten Patienten. Schlussfolgerung Die Behandlung der proximalen Humerusfraktur bleibt weiterhin eine individuelle Entscheidung abhängig von Funktionsanspruch, Alter und Komorbiditäten. Die konservative Therapie kann in Erwägung gezogen werden, teils auch bei formell bestehender Operationsindikation (v. a. 2‑ und 3‑Part-Frakturen), da sich hiermit vergleichbare Langzeitergebnisse mit hoher Patientenzufriedenheit und reduziertem (perioperativem) Risiko erzielen lassen

Rate-Induced Transitions in Networked Complex Adaptive Systems: Exploring Dynamics and Management Implications Across Ecological, Social, and Socioecological Systems

Complex adaptive systems (CASs), from ecosystems to economies, are open systems and inherently dependent on external conditions. While a system can transition from one state to another based on the magnitude of change in external conditions, the rate of change -- irrespective of magnitude -- may also lead to system state changes due to a phenomenon known as a rate-induced transition (RIT). This study presents a novel framework that captures RITs in CASs through a local model and a network extension where each node contributes to the structural adaptability of others. Our findings reveal how RITs occur at a critical environmental change rate, with lower-degree nodes tipping first due to fewer connections and reduced adaptive capacity. High-degree nodes tip later as their adaptability sources (lower-degree nodes) collapse. This pattern persists across various network structures. Our study calls for an extended perspective when managing CASs, emphasizing the need to focus not only on thresholds of external conditions but also the rate at which those conditions change, particularly in the context of the collapse of surrounding systems that contribute to the focal system's resilience. Our analytical method opens a path to designing management policies that mitigate RIT impacts and enhance resilience in ecological, social, and socioecological systems. These policies could include controlling environmental change rates, fostering system adaptability, implementing adaptive management strategies, and building capacity and knowledge exchange. Our study contributes to the understanding of RIT dynamics and informs effective management strategies for complex adaptive systems in the face of rapid environmental change.Comment: 25 pages, 4 figures, 1 box, supplementary informatio

Adhesins as targets for vaccine development.

Blocking the primary stages of infection, namely bacterial attachment to host cell receptors and colonization of the mucosal surface, may be the most effective strategy to prevent bacterial infections. Bacterial attachment usually involves an interaction between a bacterial surface protein called an adhesin and the host cell receptor. Recent preclinical vaccine studies with the FimH adhesin (derived from uropathogenic Escherichia coli) have confirmed that antibodies elicited against an adhesin can impede colonization, block infection, and prevent disease. The studies indicate that prophylactic vaccination with adhesins can block bacterial infections. With recent advances in the identification, characterization, and isolation of other adhesins, similar approaches are being explored to prevent infections, from otitis media and dental caries to pneumonia and sepsis

ARGONAUTE10 and ARGONAUTE1 Regulate the Termination of Floral Stem Cells through Two MicroRNAs in Arabidopsis

Stem cells are crucial in morphogenesis in plants and animals. Much is known about the mechanisms that maintain stem cell fates or trigger their terminal differentiation. However, little is known about how developmental time impacts stem cell fates. Using Arabidopsis floral stem cells as a model, we show that stem cells can undergo precise temporal regulation governed by mechanisms that are distinct from, but integrated with, those that specify cell fates. We show that two microRNAs, miR172 and miR165/166, through targeting APETALA2 and type III homeodomain-leucine zipper (HD-Zip) genes, respectively, regulate the temporal program of floral stem cells. In particular, we reveal a role of the type III HD-Zip genes, previously known to specify lateral organ polarity, in stem cell termination. Both reduction in HD-Zip expression by over-expression of miR165/166 and mis-expression of HD-Zip genes by rendering them resistant to miR165/166 lead to prolonged floral stem cell activity, indicating that the expression of HD-Zip genes needs to be precisely controlled to achieve floral stem cell termination. We also show that both the ubiquitously expressed ARGONAUTE1 (AGO1) gene and its homolog AGO10, which exhibits highly restricted spatial expression patterns, are required to maintain the correct temporal program of floral stem cells. We provide evidence that AGO10, like AGO1, associates with miR172 and miR165/166 in vivo and exhibits “slicer” activity in vitro. Despite the common biological functions and similar biochemical activities, AGO1 and AGO10 exert different effects on miR165/166 in vivo. This work establishes a network of microRNAs and transcription factors governing the temporal program of floral stem cells and sheds light on the relationships among different AGO genes, which tend to exist in gene families in multicellular organisms

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Postsynaptic Serine Racemase Regulates NMDA Receptor Function.

d-serine is the primary NMDAR coagonist at mature forebrain synapses and is synthesized by the enzyme serine racemase (SR). However, our understanding of the mechanisms regulating the availability of synaptic d-serine remains limited. Though early studies suggested d-serine is synthesized and released from astrocytes, more recent studies have demonstrated a predominantly neuronal localization of SR. More specifically, recent work intriguingly suggests that SR may be found at the postsynaptic density, yet the functional implications of postsynaptic SR on synaptic transmission are not yet known. Here, we show an age-dependent dendritic and postsynaptic localization of SR and d-serine by immunohistochemistry and electron microscopy in mouse CA1 pyramidal neurons. In addition, using a single-neuron genetic approach in SR conditional KO mice from both sexes, we demonstrate a cell-autonomous role for SR in regulating synaptic NMDAR function at Schaffer collateral (CA3)-CA1 synapses. Importantly, single-neuron genetic deletion of SR resulted in the elimination of LTP at 1 month of age, which could be rescued by exogenous d-serine. Interestingly, there was a restoration of LTP by 2 months of age that was associated with an upregulation of synaptic GluN2B. Our findings support a cell-autonomous role for postsynaptic neuronal SR in regulating synaptic NMDAR function and suggests a possible autocrine mode of d-serine action.SIGNIFICANCE STATEMENT NMDARs are key regulators of neurodevelopment and synaptic plasticity and are unique in their requirement for binding of a coagonist, which is d-serine at most forebrain synapses. However, our understanding of the mechanisms regulating synaptic d-serine availability remains limited. d-serine is synthesized in the brain by the neuronal enzyme serine racemase (SR). Here, we show dendritic and postsynaptic localization of SR and d-serine in CA1 pyramidal neurons. In addition, using single-neuron genetic deletion of SR, we establish a role of postsynaptic SR in regulating NMDAR function. These results support an autocrine mode of d-serine action at synapses