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This is a randomized trial (ATHENA study) in de novo kidney transplant patients to compare everolimus versus mycophenolic acid (MPA) with similar tacrolimus exposure in both groups, or everolimus with concomitant tacrolimus or cyclosporine (CsA), in an unselected population. In this 12-month, multicenter, open-label study, de novo kidney transplant recipients were randomized to everolimus with tacrolimus (EVR/TAC), everolimus with CsA (EVR/CsA) or MPA with tacrolimus (MPA/TAC), with similar tacrolimus exposure in both groups. Non-inferiority of the primary end point (estimated glomerular filtration rate [eGFR] at month 12), assessed in the per-protocol population of 338 patients, was not shown for EVR/TAC or EVR/CsA versus MPA/TAC. In 123 patients with TAC levels within the protocol-specified range, eGFR outcomes were comparable between groups. The mean increase in eGFR during months 1 to 12 post-transplant, analyzed post hoc, was similar with EVR/TAC or EVR/CsA versus MPA/TAC. The incidence of treatment failure (biopsy proven acute rejection, graft loss or death) was not significant for EVR/TAC but significant for EVR/CsA versus MPA/TAC. Most biopsy-proven acute rejection events in this study were graded mild (BANFF IA). There were no differences in proteinuria between groups. Cytomegalovirus and BK virus infection were significantly more frequent with MPA/TAC. Thus, everolimus with TAC or CsA showed comparable efficacy to MPA/TAC in de novo kidney transplant patients. Non-inferiority of renal function, when pre-specified, was not shown, but the mean increase in eGFR from month 1 to 12 was comparable to MPA/TAC.
This paper investigates what we can learn from the financial crisis about the link between accounting and financial stability. The picture that emerges ten years after the crisis is substantially different from the picture that dominated the accounting debate during and shortly after the crisis. Widespread claims about the role of fair-value (or mark-to-market) accounting in the crisis have been debunked. However, we identify several other core issues for the link between accounting and financial stability. Our analysis suggests that, going into the financial crisis, banks’ disclosures about relevant risk exposures were relatively sparse. Such disclosures came later after major concerns about banks’ exposures had arisen in markets. Similarly, banks delayed the recognition of loan losses. Banks’ incentives seem to drive this evidence, suggesting that reporting discretion and enforcement deserve careful consideration. In addition, bank regulation through its interlinkage with financial accounting may have dampened banks’ incentives for corrective actions. Our analysis illustrates that a number of serious challenges remain if accounting and financial reporting are to contribute to financial stability.
We examine the degree to which competition amongst lenders interacts with the cyclicality in lending standards using a simple measure, the average physical distance of borrowers from banks’ branches. We propose that this novel measure captures the extent to which lenders are willing to stretch their lending portfolio. Consistent with this idea, we find a significant cyclical component in the evolution of lending distances. Distances widen considerably when credit conditions are lax and shorten considerably when credit conditions become tighter. Next, we show that a sharp departure from the trend in distance between banks and borrowers is indicative of increased risk taking. Finally, we provide evidence that as competition in banks’ local markets increases, their willingness to make loans at greater distance increases. Since average lending distance is easily measurable, it is potentially a useful measure for bank supervisors.
Behavior is characterized by sequences of goal oriented conducts, such as food uptake, socializing and resting. Classically, one would define for each task a corresponding satisfaction level, with the agent engaging, at a given time, in the activity having the lowest satisfaction level. Alternatively, one may consider that the agent follows the overarching objective to generate sequences of distinct activities. To achieve a balanced distribution of activities would then be the primary goal, and not to master a specific task. In this setting the agent would show two types of behaviors, task-oriented and task-searching phases, with the latter interseeding the former. We study the emergence of autonomous task switching for the case of a simulated robot arm. Grasping one of several moving objects corresponds in this setting to a specific activity. Overall, the arm should follow a given object temporarily and then move away, in order to search for a new target and reengage. We show that this behavior can be generated robustly when modeling the arm as an adaptive dynamical system. The dissipation function is in this approach time dependent. The arm is in a dissipative state when searching for a nearby object, dissipating energy on approach. Once close, the dissipation function starts to increase, with the eventual sign change implying that the arm will take up energy and wander off. The resulting explorative state ends when the dissipation function becomes again negative and the arm selects a new target. We believe that our approach may be generalized to generate self-organized sequences of activities in general.
Beauty is the single most frequently and most broadly used aesthetic virtue term. The present study aimed at providing higher conceptual resolution to the broader notion of beauty by comparing it with three closely related aesthetically evaluative concepts which are likewise lexicalized across many languages: elegance, grace(fulness), and sexiness. We administered a variety of questionnaires that targeted perceptual qualia, cognitive and affective evaluations, as well as specific object properties that are associated with beauty, elegance, grace, and sexiness in personal looks, movements, objects of design, and other domains. This allowed us to reveal distinct and highly nuanced profiles of how a beautiful, elegant, graceful, and sexy appearance is subjectively perceived. As aesthetics is all about nuances, the fine-grained conceptual analysis of the four target concepts of our study provides crucial distinctions for future research.
Visibility and digital accessibility of the School of Salamanca in a linked open-data environment
(2019)
This paper raises the bibliographic and technological approach to increasing visibility and accessibility of the work of the School of Salamanca in the current technological state of the web. The objective is to avoid the cultural effect of not acting in this field, for which authors draw an analogy with Plantin's privilege in 16th-Century Spanish printing. The Virtual Library of the School of Salamanca is described as a Linked Open-Data resource about the authors of this school and their digitized works, in which the relationships between authors and concepts are crucial. For this purpose, different properties of the DBpedia ontology are used, and the descriptions of the authors are systematically linked to other Linked Open-Data resources. All descriptions (authors, works and concepts) are offered in Europeana Data Model and MARC 21. Also discussed are the advantages of Wikipedia and Wikidata in increasing visibility.
A summary of this text was presented at the international conference organized by the Max Planck Institute for the History of European Law: "The School of Salamanca: A Case of Global Knowledge Production?", held in Buenos Aires from 24th to 26th October 2018.
In this exploratory article, we consider the future of Deutsche Bank and Commerzbank and develop a new approach to the topic: instead of a merger of DB and CB we propose to consider a partial merger of the IT and related back office functions in order to create the basis for an Open Banking platform in Germany. Such a platform would act as a cross-institutional infrastructure company in which the participating banks develop a common data and IT platform (while respecting the data protection regulations). Significant parts of the transaction processes would be pooled by the institutions and executed by the Open Banking platform. Moreover, the institutions remain legally independent and compete with each other at the level of products and services that are developed and produced using just this common data and IT platform – “national champions” would not be created.
But such an “Open Banking Platform” could become even the nucleus of a European Banking platform that could be competitive with existing global data platforms from the USA and China which are already offering financial services and are likely to expand their offerings in the foreseeable future. The proposed model of an open data platform for banks prevents the emergence of national champions and supports the main goal of the banking union: creation of a financial system, in which single banks can be resolved without provoking a systemic crisis and forcing taxpayers to finance bailouts.
Purpose: The purpose of this study was to report our initial experience of hyaluronic acid gel injection (HGI) in the vesicovaginal septum (VVS) for bladder dose reduction in brachytherapy (BT) for uterine cervical carcinoma.
Material and methods: Between September 2016 and May 2018, 15 uterine cervical cancer patients received HGI in the VVS as a part of their definitive radiotherapy (RT) treatment consisting of external beam radiation therapy (EBRT) with additional BT. Of those, 9 patients received BT both with and without HGI, and remaining 6 patients were excluded because these 6 patients received HGI in the VVS for all BT fractions. All 9 patients received HGI in the rectovaginal septum. For these patients, the dosimetric parameters bladder D2cc, HR-CTV D90, and rectum D2cc were selected, and two groups were generated (BT with vs. without HGI in the VVS) for dosimetric comparison.
Results: The median cumulative EQD2 for HR-CTV, rectum D2cc, and bladder D2cc for the 9 patients were 73.3, 52.8, and 67.1, respectively. While no statistical difference could be detected for rectal dose reduction, bladder dose was significantly less in the group with HGI in the VVS compared to that without (449 cGy [range, 416-566, 1SD = 66.1] vs. 569 cGy [range, 449-647, 1SD = 59.5], p = 0.033), with no compromising of target coverage. Although it did not reach statistically significance, there was a trend toward better HR-CTV D90 in the group with HGI compared to that without HGI in the VVS (713 cGy vs. 706 cGy, p = 0.085). No severe bleeding, hematuria, bladder wall injury, or urethral injury requiring hospitalization was experienced in association with HGI in the VVS.
Conclusions: HGI in the VVS can be performed safely and can effectively reduce the bladder dose in BT for uterine cervical cancer patients.
Bone marrow and plasma FGF‐23 in heart failure patients : novel insights into the heart–bone axis
(2019)
Aims: Fibroblast growth factor 23 (FGF‐23) is known to be elevated in patients with congestive heart failure (CHF). As FGF‐23 is expressed in the bone but can also be expressed in the myocardium, the origin of serum FGF‐23 in CHF remains unclear. It is also unclear if FGF‐23 expressed in the bone is associated with outcome in CHF. The aim of the present study was to investigate FGF‐23 levels measured in bone marrow plasma (FGF‐23‐BM) and in peripheral blood (FGF‐23‐P) in CHF patients to gain further insights into the heart–bone axis of FGF‐23 expression. We also investigated possible associations between FGF‐23‐BM as well as FGF‐23‐P and outcome in CHF patients.
Methods and results: We determined FGF‐23‐P and FGF‐23‐BM levels in 203 CHF patients (85% male, mean age 61.3 years) with a left ventricular ejection fraction (LVEF) ≤45% and compared them with those of 48 healthy controls (48% male, mean age 39.2 years). We investigated the association between FGF‐23‐BM and FGF‐23‐P with all‐cause mortality in CHF patients, 32 events, median follow‐up 1673 days, interquartile range [923, 1828]. FGF‐23‐P (median 60.3 vs. 22.0 RU/mL, P < 0.001) and FGF‐23‐BM (median 130.7 vs. 93.1 RU/mL, P < 0.001) levels were higher in CHF patients compared with healthy controls. FGF‐23‐BM levels were significantly higher than FGF‐23‐P levels in both CHF patients and in healthy controls (P < 0.001). FGF‐23‐P and FGF‐23‐BM correlated significantly with LVEF (r = −0.37 and r = −0.33, respectively), N terminal pro brain natriuretic peptide levels (r = 0.57 and r = 0.6, respectively), New York Heart Association status (r = 0.28 and r = 0.25, respectively), and estimated glomerular filtration rate (r = −0.43 and r = −0.41, respectively) (P for all <0.001) and were independently associated with all‐cause mortality in CHF patients after adjustment for LVEF, estimated glomerular filtration rate, New York Heart Association status, and N terminal pro brain natriuretic peptide, hazard ratio 2.71 [confidence interval: 1.18–6.20], P = 0.018, and hazard ratio 2.80 [confidence interval: 1.19–6.57], P = 0.018, respectively.
Conclusions: In CHF patients, FGF‐23 is elevated in bone marrow plasma and is independently associated with heart failure severity and all‐cause mortality. The failing heart seems to interact via FGF‐23 within a heart–bone axis.
Specialized de novo assemblers for diverse datatypes have been developed and are in widespread use for the analyses of single-cell genomics, metagenomics and RNA-seq data. However, assembly of large sequencing datasets produced by modern technologies is challenging and computationally intensive. In-silico read normalization has been suggested as a computational strategy to reduce redundancy in read datasets, which leads to significant speedups and memory savings of assembly pipelines. Previously, we presented a set multi-cover optimization based approach, ORNA, where reads are reduced without losing important k-mer connectivity information, as used in assembly graphs. Here we propose extensions to ORNA, named ORNA-Q and ORNA-K, which consider a weighted set multi-cover optimization formulation for the in-silico read normalization problem. These novel formulations make use of the base quality scores obtained from sequencers (ORNA-Q) or k-mer abundances of reads (ORNA-K) to improve normalization further. We devise efficient heuristic algorithms for solving both formulations. In applications to human RNA-seq data, ORNA-Q and ORNA-K are shown to assemble more or equally many full length transcripts compared to other normalization methods at similar or higher read reduction values. The algorithm is implemented under the latest version of ORNA (v2.0, https://github.com/SchulzLab/ORNA).