Kosten aus einer asymmetrischen Informationsverteilung zwischen Abschlussprüfer und Mandant

Die Einschätzungen des Abschlussprüfers über die Eigenschaften eines Mandanten fließen in die Annahme eines Prüfungsauftrages sowie die Festsetzung der Prüfungsgebühr ein. Der vorliegende Beitrag analysiert, wie die Informationsasymmetrie über das beim Mandanten vorliegende Risiko in der Gebührensetzung bei Erst- und Folgeprüfungen berücksichtigt werden kann. Für den Mandanten werden dabei zwei Risikotypen unterschieden, so dass die Informationsunsicherheit sich darauf bezieht, ob ein hohes oder ein geringes Prüfungs- oder Auftragsrisiko vorliegt. Ein Vergleich der Gebührensetzung bei symmetrischer und asymmetrischer Information zeigt, wann der Abschlussprüfer oder der Mandant die Kosten der vorvertraglichen Informationsasymmetrie trägt. Im Ergebnis ist festzuhalten, dass es bei asymmetrischer Information allein von den mandantenspezifischen Prüfungskosten abhängig ist, ob der riskante oder nicht riskante Mandant die Kosten trägt. Die Zusammensetzung des Mandantenportfolios beim Abschlussprüfer nimmt hingegen keinen Einfluss auf die Kosten, die der Informationsasymmetrie zurechenbar sind

Audit market segmentation - The impact of mid-tier audit firms on competition -

It is a global phenomenon that more than 75% of a developed country's listed companies are clients of a Big-4 auditor. However, the economic consequences of this concentration are inconclusive. On the one hand, a kind of `similarity'-hypothesis suggests that the existence of a few global auditors might induce Bertrand-oligopoly-like national audit market structures due to a lack of auditor differentiation in size and quality. Consequently, virtually no profits should be gained by the audit companies. On the other hand, the “too-big-to-fail”-hypothesis suggests that governmental bodies might refrain from sanctions against Big-4 auditors, because they are afraid of further consolidating an oligopolistic market structure by dissolving another major supplier. In the long run, impairing competition could result in rather high audit profits. Irrespective of which hypothesis they adhere to, regulating authorities recently recognized enabling mid-tier auditors to serve large multinational clients as a promising cure for the aforementioned problems. Accordingly, the goal of our paper is to develop a comprehensive model of audit market segmentation for analyzing the competitive impact of mid-tier auditors. As a modeling device we make use of a Hotelling setting, which has several advantages: Firstly, it depicts strategically motivated product differentiation, i.e., auditors supplying different quality levels can be analyzed. Secondly, in contrast to perfect competition models, in our model most audit firms realize non-negative profits better describing business practice. Thirdly, explicitly matching suppliers and customers allows to distinguish supply-side and demand-side audit quality. Major results of our analysis are the following: A loss in high-quality auditors' flexibility to customize their audit programs is followed by an increase of audit quality offered by mid-tier firms. But, if mid-tier firms left the audit market, the Big-4 firms would raise the offered quality level, incurring growing profits as well. Further, the “market power” hypothesis stating that greater market shares imply rising fees can be supported theoretically.

Audit market segmentation : the impact of mid-tier audit firms on competition

It is a global phenomenon that more than 75% of a developed country's listed companies are clients of a Big-4 auditor. However, the economic consequences of this concentration are inconclusive. On the one hand, a kind of similarity'-hypothesis suggests that the existence of a few global auditors might induce Bertrand-oligopoly-like national audit market structures due to a lack of auditor differentiation in size and quality. Consequently, virtually no profits should be gained by the audit companies. On the other hand, the “too-big-to-fail”-hypothesis suggests that governmental bodies might refrain from sanctions against Big-4 auditors, because they are afraid of further consolidating an oligopolistic market structure by dissolving another major supplier. In the long run, impairing competition could result in rather high audit profits. Irrespective of which hypothesis they adhere to, regulating authorities recently recognized enabling mid-tier auditors to serve large multinational clients as a promising cure for the aforementioned problems. Accordingly, the goal of our paper is to develop a comprehensive model of audit market segmentation for analyzing the competitive impact of mid-tier auditors. As a modeling device we make use of a Hotelling setting, which has several advantages: Firstly, it depicts strategically motivated product differentiation, i.e., auditors supplying different quality levels can be analyzed. Secondly, in contrast to perfect competition models, in our model most audit firms realize non-negative profits better describing business practice. Thirdly, explicitly matching suppliers and customers allows to distinguish supply-side and demand-side audit quality. Major results of our analysis are the following: A loss in high-quality auditors' flexibility to customize their audit programs is followed by an increase of audit quality offered by mid-tier firms. But, if mid-tier firms left the audit market, the Big-4 firms would raise the offered quality level, incurring growing profits as well. Further, the “market power” hypothesis stating that greater market shares imply rising fees can be supported theoretically

Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes’ availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy

Lgr5+ stem and progenitor cells reside at the apex of a heterogeneous embryonic hepatoblast pool.

During mouse embryogenesis, progenitors within the liver known as hepatoblasts give rise to adult hepatocytes and cholangiocytes. Hepatoblasts, which are specified at E8.5-E9.0, have been regarded as a homogeneous progenitor population that initiate differentiation from E13.5. Recently, scRNA-seq analysis has identified sub-populations of transcriptionally distinct hepatoblasts at E11.5. Here, we show that hepatoblasts are not only transcriptionally but also functionally heterogeneous, and that a subpopulation of E9.5-E10.0 hepatoblasts exhibit a previously unidentified early commitment to cholangiocyte fate. Importantly, we also identify a subpopulation constituting 2% of E9.5-E10.0 hepatoblasts that express the adult stem cell marker Lgr5, and generate both hepatocyte and cholangiocyte progeny that persist for the lifespan of the mouse. Combining lineage tracing and scRNA-seq, we show that Lgr5 marks E9.5-E10.0 bipotent liver progenitors residing at the apex of a hepatoblast hierarchy. Furthermore, isolated Lgr5+ hepatoblasts can be clonally expanded in vitro into embryonic liver organoids, which can commit to either hepatocyte or cholangiocyte fates. Our study demonstrates functional heterogeneity within E9.5 hepatoblasts and identifies Lgr5 as a marker for a subpopulation of bipotent liver progenitors.M.H. is a Wellcome Trust Sir Henry Dale Fellow and is jointly funded by the Wellcome Trust and the Royal Society (104151/Z/14/Z); M.H. and N.P. are funded by a Horizon 2020 grant (LSFM4LIFE). C.H. was funded by a Cambridge Stem Cell Institute Seed funding for interdisciplinary research awarded to M.H. and B.D.S., B.D.S acknowledges funding from the Royal Society E.P. Abraham Research Professorship (RP\R1\180165) and Wellcome Trust (098357/Z/12/Z). W.L. and B.G. were supported by programmatic funding from the Wellcome Trust, CRUK and Bloodwise, core infrastructure support from the Wellcome and MRC to the Wellcome & MRC Cambridge Stem Cell Institute, and an MRC Clinical Research Infrastructure grant supporting single cell molecular analysis. S.R. was funded on a Herchel-Smith Fellowship. The authors acknowledge core funding to the Gurdon Institute from the Wellcome Trust (092096) and CRUK (C6946/A14492)

Umberto Eco, Narratives of Conspiracy and the Anti-Semite Among Us

http://www.quest-cdecjournal.it/discussion.php?id=3

Identification of DNA sequence variation in Campylobacter jejuni strains associated with the Guillain-Barre syndrome by high-throughput AFLP analysis.

BACKGROUND: Campylobacter jejuni is the predominant cause of antecedent infection in post-infectious neuropathies such as the Guillain-Barre (GBS) and Miller Fisher syndromes (MFS). GBS and MFS are probably induced by molecular mimicry between human gangliosides and bacterial lipo-oligosaccharides (LOS). This study describes a new C. jejuni-specific high-throughput AFLP (htAFLP) approach for detection and identification of DNA polymorphism, in general, and of putative GBS/MFS-markers, in particular. RESULTS: We compared 6 different isolates of the "genome strain" NCTC 11168 obtained from different laboratories. HtAFLP analysis generated approximately 3000 markers per stain, 19 of which were polymorphic. The DNA polymorphisms could not be confirmed by PCR-RFLP analysis, suggesting a baseline level of 0.6% AFLP artefacts. Comparison of NCTC 11168 with 4 GBS-associated strains revealed 23 potentially GBS-specific markers, 17 of which were identified by DNA sequencing. A collection of 27 GBS/MFS-associated and 17 enteritis control strains was analyzed with PCR-RFLP tests based on 11 of these markers. We identified 3 markers, located in the LOS biosynthesis genes cj1136, cj1138 and cj1139c

MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells

Dendritic cells (DCs) produce major histocompatibility complex II (MHCII) in large amounts to function as professional antigen presenting cells. Paradoxically, DCs also ubiquitinate and degrade MHCII in a constitutive manner. Mice deficient in the MHCII-ubiquitinating enzyme membrane-anchored RING-CH1, or the ubiquitin-acceptor lysine of MHCII, exhibit a substantial reduction in the number of regulatory T (Treg) cells, but the underlying mechanism was unclear. Here we report that ubiquitin-dependent MHCII turnover is critical to maintain homeostasis of lipid rafts and the tetraspanin web in DCs. Lack of MHCII ubiquitination results in the accumulation of excessive quantities of MHCII in the plasma membrane, and the resulting disruption to lipid rafts and the tetraspanin web leads to significant impairment in the ability of DCs to engage and activate thymocytes for Treg cell differentiation. Thus, ubiquitin-dependent MHCII turnover represents a novel quality-control mechanism by which DCs maintain homeostasis of membrane domains that support DC's Treg cell-selecting function

Safe use of proton pump inhibitors in patients with cirrhosis

Aims: Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis. Methods: A systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child–Turcotte–Pugh (CTP) classification. Results: A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having ‘no additional risks known’. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. Conclusions: We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients