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Matching Supply and Demand of Electricity Network- Supportive Flexibility: A Case Study with Three Comprehensible Matching Algorithms
No full textDue to an ongoing energy transition, electricity networks are increasingly challenged by situations where local electrical power demands are high but local generation is low and vice versa. This finally leads to a growing number of technical problems. To solve these problems in the short-term, the electrical power of load and generation must be adjusted as available flexibility. In zonal electricity systems, one often discussed concept to utilize flexibility is local flexibility markets. Based on auction theory, we provide a comprehensible framework for the use of network-supportive flexibility in general. In this context, we discuss the problem of matching supply and demand. We introduce three matching approaches that can be applied and adapted for different network situations. In addition to a qualitative description of the three approaches, we present a case study of an exemplary distribution network and explore different scenarios to demonstrate the utility of the algorithms. We compare the three approaches on a qualitative level with quantitative inputs from the case study. The comparison considers the specific cost, flexible energy, ensured demand coverage, data minimization, computational effort and the transferability of the three approaches
Offset carbon emissions or pay a price premium for avoiding them? A cross-country analysis of motives for climate protection activities
No full textThis paper contributes to the economic literature on pure and impure public goods by considering two alternatives for contributing to the public good climate protection: compensating carbon emissions from conventional consumption or paying higher prices for climate-friendly products. We analytically and empirically examine a wide range of motives and their impact on individuals’ choice in favor of these two alternatives. Relying on data from representative surveys among more than 2000 participants from Germany and the USA, our results indicate that environmental awareness, warm glow motives, and the desire to set a good example significantly motivate the choice of both climate protection activities in both countries. However, some motives differ considerably between both alternatives and countries. A green identity enhances the willingness to pay a price premium for climate-friendly goods or services in Germany, while social norms seem to be of much higher relevance in the USA. Our results further suggest that the choice of climate protection activities, especially of carbon offsetting, entails a high degree of uncertainty
Menstrual blood-derived mesenchymal stromal cells: impact of preconditioning on the cargo of extracellular vesicles as potential therapeutics
No full textMesenchymal stromal cells (MSCs) have been shown to exert their therapeutic effects through the secretion of broad spectrum of paracrine factors, including extracellular vesicles (EVs). Accordingly, EVs are being pursued as a promising alternative to cell-based therapies. Menstrual blood-derived stromal cells (MenSCs) are a type of MSC that, due to their immunomodulatory and regenerative properties, have emerged as an innovative source. Additionally, new strategies of cell priming may potentially alter the concentration and cargo of released EVs, leading to modification of their biological properties. In this study, we aimed to characterize the EVs released by MenSCs and compare their therapeutic potential under three different preconditioning conditions (proinflammatory stimuli, physioxia, and acute hypoxia).
MenSCs were isolated from five healthy women. Following culturing to 80% confluence, MenSCs were exposed to different priming conditions: basal (21% O2), proinflammatory stimuli (IFNγ and TNFα, 21% O2), physioxia (1–2% O2), and acute hypoxia (< 1% O2) for 48–72 h. Conditioned media from MenSCs was collected after 48 h and EVs were isolated by a combination of ultra-filtration and differential centrifugation. An extensive characterization ranging from nano-flow cytometry (nFC) to quantitative high-throughput shotgun proteomics was performed. Bioinformatics analyses were used to derive hypotheses on their biological properties.
No differences in the morphology, size, or number of EVs released were detected between priming conditions. The proteome analysis associated with basal MenSC-EVs prominently revealed their immunomodulatory and regenerative capabilities. Furthermore, quantitative proteomic analysis of differentially produced MenSC-EVs provided sufficient evidence for the utility of the differential preconditioning in purpose-tailoring EVs for their therapeutic application: proinflammatory priming enhanced the anti-inflammatory, regenerative and immunomodulatory capacity in the innate response of EVs, physioxia priming also improves tissue regeneration, angiogenesis and their immunomodulatory capacity targeting on the adaptive response, while acute hypoxia priming, increased hemostasis and apoptotic processes regulation in MenSC-EVs, also by stimulating immunomodulation mainly through the adaptive response.
Priming of MenSCs under proinflammatory and hypoxic conditions affected the cargo proteome of EVs released, resulting in different therapeutic potential, and thus warrants experimental exploration with the aim to generate better-defined MSC-derived bioproducts.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside
No full textBackground: Rhabdomyosarcoma (RMS) is the most common pediatric softtissue
malignancy, characterized by high clinicalopathological and molecular
heterogeneity. Preclinical in vivo models are essential for advancing our
understanding of RMS oncobiology and developing novel treatment strategies.
However, the diversity of scholarly data on preclinical RMS studies may challenge
scientists and clinicians. Hence, we performed a systematic literature survey of
contemporary RMS mouse models to characterize their phenotypes and assess
their translational relevance.
Methods: We identified papers published between 01/07/2018 and 01/07/2023
by searching PubMed and Web of Science databases.
Results: Out of 713 records screened, 118 studies (26.9%) were included in the
qualitative synthesis. Cell line-derived xenografts (CDX) were the most
commonly utilized (n = 75, 63.6%), followed by patient-derived xenografts
(PDX) and syngeneic models, each accounting for 11.9% (n = 14), and
genetically engineered mouse models (GEMM) (n = 7, 5.9%). Combinations of
different model categories were reported in 5.9% (n = 7) of studies. One study
employed a virus-induced RMS model. Overall, 40.0% (n = 30) of the studies
utilizing CDX models established alveolar RMS (aRMS), while 38.7% (n = 29) were
embryonal phenotypes (eRMS). There were 20.0% (n = 15) of studies that involved
a combination of both aRMS and eRMS subtypes. In one study (1.3%), the RMS
phenotype was spindle cell/sclerosing. Subcutaneous xenografts (n = 66, 55.9%)
were more frequently used compared to orthotopic models (n = 29, 24.6%).
Notably, none of the employed cell lines were derived from primary untreated
tumors. Only a minority of studies investigated disseminated RMS phenotypes
(n = 16, 13.6%). The utilization areas of RMS models included testing drugs (n =
64, 54.2%), studying tumorigenesis (n = 56, 47.5%), tumor modeling (n = 19,
16.1%), imaging (n = 9, 7.6%), radiotherapy (n = 6, 5.1%), long-term effects related
to radiotherapy (n = 3, 2.5%), and investigating biomarkers (n = 1, 0.8%). Notably,
no preclinical studies focused on surgery.
Conclusions: This up-to-date review highlights the need for mouse models with
dissemination phenotypes and cell lines from primary untreated tumors.
Furthermore, efforts should be directed towards underexplored areas such as
surgery, radiotherapy, and biomarkers.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
The significance of KCNJ 15 / KCNJ 16 interactions in a novel complex tubular kidney disease
No full textIn den vergangenen Jahrzehnten wurden seltene Krankheiten erforscht, die durch eine
Dysfunktion von Ionenkanälen in den Tubuluszellen der Niere hervorgerufen werden und
mit renalem Salzverlust einhergehen. Vor allem das EAST/SeSAME-Syndrom wird seit
2009 untersucht, das auf eine Mutation in KCNJ 10 zurückgeht und unter anderem mit
Epilepsie, Ataxie, Hörverlust, metabolischer Alkalose und renalem Salzverlust
einhergeht.
Nun wurde eine neuartige Erkrankung entdeckt, die auf eine Mutation in KCNJ 16
zurückzuführen ist und ähnliche Symptome wie das bereits bekannte EAST/SeSAMESyndrom
hervorruft. Es wurden bisher sechs betroffene Patienten mit fünf
verschiedenen Mutationen (Missense und Nonsense-Mutationen) in KCNJ 16
identifiziert, deren Symptomausprägung und Zeitpunkt der Diagnosestellung
unterschiedlich sind. Zwei der Patienten weisen eine homozygote Mutation in KCNJ 16
(T64I bzw. R137C) auf, die anderen vier Patienten sind compound-heterozygot (bei zwei
Patienten I132R, R176X; bei zwei Patienten R137C, R176X; bei einem Patienten I132R,
P250L). Die Mutationen führen zu veränderten Aminosäuren am C- und N-Terminus
sowie im Selektivitätsfilter des Kaliumkanals. Die Patienten leiden an Hypokaliämie,
sensorineuraler Schwerhörigkeit, renalem Salzverlust und anders als Patienten mit
EAST/SeSAME-Syndrom an metabolischer Azidose.
Um den Pathomechanismus dahinter näher zu verstehen, wurde in der vorliegenden
Arbeit der heteromere Kanal Kir 4.2/5.1 (KCNJ 15/16) untersucht, der vor allem im
proximalen Tubulus der Niere exprimiert wird, wo auch der pH-Wert reguliert wird.
Für die Durchführung der Versuche wurde KCNJ 16 mittels side directed mutagenisis
dahingehend genetisch verändert, dass die Basen der DNA den identifizierten
Mutationen entsprechend ausgetauscht wurden.
Es wurden Proteininteraktionsstudien mittels Proximity ligation assay und Co-
Immunoprecipitation durchgeführt, um die Interaktion zwischen den Kanaluntereinheiten
Kir 4.2 und Kir 5.1 zu untersuchen. Dabei wurden humane embryonale Nierenzellen
(HEK) und immortalisierte Fibroblasten der Niere (Cos7) mit der genetisch veränderten
DNA transfiziert und in der Zellkultur bebrütet, sodass diese die mutierten Kanäle
synthetisierten und exprimierten. Dadurch konnte nachgewiesen werden, dass Kir 4.2
sowohl mit dem Wildtyp als auch mit allen fünf mutierten Formen von Kir 5.1 interagiert
und die Symptome der Patienten nicht durch gänzlich fehlende Interaktion der
Kanaluntereinheiten erklärt werden können.
Anschließend wurden Lumineszenzversuche mit Xenopus laevis Oozyten durchgeführt,
um die Quantität der exprimierten Kanäle der mutierten Varianten mit der der
Wildtypkanäle zu vergleichen. Dabei wurde den Oozyten die genetisch veränderte RNA
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injiziert, sodass diese die entsprechenden Kanäle mit den identifizierten Mutationen
exprimierten. Diese Versuche zeigten, dass quantitativ weniger der mutierten Kanäle an
die Zelloberfläche gelangten als der Wildtypkanäle. Die geringere Kanaldichte ist also
einer der Gründe für einen geringeren Ionenstrom von Kalium durch die Zellmembran
und kann so die davon hervorgerufenen Symptome der Betroffenen erklären.
In der vorliegenden Arbeit wurde an der ersten bekannten Erkrankung geforscht, die auf
eine Mutation in KCNJ 16 zurückzuführen ist. Sie liefert damit wichtige neue
Informationen für das tiefer gehende Verständnis von Kir 5.1, der Funktion von
Einwärtsgleichrichtern in der Niere und des damit verbundenen Elektrolyt- und Säure-
Basen-Gleichgewichts des Körpers.In recent decades, rare diseases have been researched that are caused by dysfunction
of ion channels in the tubular cells of the kidney and are associated with renal salt loss.
In particular, the EAST/SeSAME syndrome has been investigated since 2009, which is
caused by a mutation in KCNJ 10 and is associated, among other things, with epilepsy,
ataxia, hearing loss, metabolic alkalosis and renal salt loss.
A new disease has now been discovered that is due to a mutation in KCNJ 16 and causes
symptoms similar to the already known EAST/SeSAME syndrome. To date, six affected
patients have been identified with five different mutations (missense and nonsense
mutations) in KCNJ 16, whose symptoms and time of diagnosis are different. Two of the
patients have a homozygous mutation in KCNJ 16 (T64I or R137C), the other four
patients are compound heterozygous (in two patients I132R, R176X; in two patients
R137C, R176X; in one patient I132R, P250L). The mutations lead to changed amino
acids at the C and N terminus as well as in the selectivity filter of the potassium channel.
Patients suffer from hypokalemia, sensorineural hearing loss, renal salt wasting and,
unlike patients with EAST/SeSAME syndrome, metabolic acidosis.
In order to understand the pathomechanism behind it in more detail, the present work
examined the heteromeric channel Kir 4.2/5.1 (KCNJ 15/16), which is mainly expressed
in the proximal tubule of the kidney, where the pH value is also regulated.
To carry out the experiments, KCNJ 16 was genetically modified using side directed
mutagenesis so that the bases of the DNA were exchanged according to the identified
mutations.
Protein interaction studies using proximity ligation assay and co-immunoprecipitation
were performed to investigate the interaction between the channel subunits Kir 4.2 and
Kir 5.1. Human embryonic kidney cells (HEK) and immortalized kidney fibroblasts (Cos7)
were transfected with the genetically modified DNA and incubated in cell culture so that
they synthesized and expressed the mutated channels. This made it possible to
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demonstrate that Kir 4.2 interacts with both the wild type and all five mutated forms of
Kir 5.1 and that the patients' symptoms cannot be explained by a complete lack of
interaction between the channel subunits.
Luminescence experiments were then carried out with Xenopus laevis oocytes to
compare the quantity of expressed channels of the mutated variants with that of the wildtype
channels. The genetically modified RNA was injected into the oocytes so that they
expressed the corresponding channels with the identified mutations. These experiments
showed that quantitatively fewer of the mutated channels reached the cell surface than
the wild-type channels. The lower channel density is one of the reasons for a lower ion
current of potassium through the cell membrane and can therefore explain the symptoms
this causes in those affected.
In the present work, research was carried out on the first known disease that can be
traced back to a mutation in KCNJ 16. It thus provides important new information for a
deeper understanding of Kir 5.1, the function of inward rectifiers in the kidney and the
associated electrolyte and acid-base balance of the body
Housing Market Convergence: Evidence from Germany
No full textThis paper analyses the convergence pattern of German housing prices and rents, employing a new dataset covering the country’s administrative districts. In addition to conventional tests for ?-convergence and ?-convergence, we apply Phillips and Sul’s (2007) approach to allow for the various heterogeneity and transitional dynamics across districts. Our results reveal no evidence of convergence across Germany or within states; instead, we discover widespread evidence of divergence and inter-state convergence, as well as support for the existence of convergence clubs. At the federal level, we identify club numbers ranging from 11 (for existing flat prices) to five (for new flat rents). At the state level, the estimated number of clubs is generally lower, ranging from zero to six
Revenue decoupling and energy consumption: Empirical evidence from the U.S. electric utilities sector
No full textEnergy efficiency provides a substantial opportunity to tackle increasing greenhouse gas emissions. However, in traditionally regulated energy markets, energy providers maximize their profits by selling electricity or heat as long as their marginal revenue exceeds their marginal costs of production. This so called ’throughput incentive’ fundamentally restricts the motivation of utilities to invest in energy efficiency. This paper therefore investigates the relation between the regulatory policy revenue decoupling, that separates utilities’ revenue from sales fluctuations, and electricity customers’ energy demand and efficiency in the U.S. To address the research question at hand, we follow recent developments in energy demand function modeling and Stochastic Frontier Analysis (SFA) estimation techniques that allow to account for persistent as well as transient efficiency. The estimation results show a signif- icant negative correlation between revenue decoupling and electricity consumption patterns. Furthermore, we find electricity customers have small transient inefficiency. However, results indicate an underlying persistent inefficiency across the entire electric sector
Protein secretion zones during overexpression of amylase within the Gram‑positive cell wall
No full textWhereas the translocation of proteins across the cell membrane has been thoroughly investigated, it is still unclear how proteins cross the cell wall in Gram-positive bacteria, which are widely used for industrial applications. We have studied the secretion of α-amylase AmyE within two different Bacillus strains, B. subtilis and B. licheniformis.
We show that a C-terminal fusion of AmyE with the fluorescent reporter mCherry is secreted via discrete patches showing very low dynamics. These are visible at many places within the cell wall for many minutes. Expression from a high copy number plasmid was required to be able to see these structures we term “secretion zones”. Zones corresponded to visualized AmyE activity on the surface of cells, showing that they release active enzymes. They overlapped with SecA signals but did not frequently co-localize with the secretion ATPase. Single particle tracking showed higher dynamics of SecA and of SecDF, involved in AmyE secretion, at the cell membrane than AmyE. These experiments suggest that SecA initially translocates AmyE molecules through the cell membrane, and then diffuses to a different translocon. Single molecule tracking of SecA suggests the existence of three distinct diffusive states of SecA, which change during AmyE overexpression, but increased AmyE secretion does not appear to overwhelm the system.
Because secretion zones were only found during the transition to and within the stationary phase, diffusion rather than passive transport based on cell wall growth from inside to outside may release AmyE and, thus, probably secreted proteins in general. Our findings suggest active transport through the cell membrane and slow, passive transition through the cell wall, at least for overexpressed proteins, in bacteria of the genus Bacillus.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Functional and hemodynamic result with the PASCAL Ace™ percutaneous mitral valve repair in patients with severe mitral valve regurgitation
No full textHintergrund: Die Edge-to-edge kathetergestützte Therapie der MI hat sich zu einer wertvollen und etablierten Behandlungsoption bei Patienten mit hochgradiger MI entwickelt, die ein hohes Operationsrisiko aufweisen. Neben dem MitraClip® ist auch das PASCAL®- kathetergestützte Klappenreparatur-System für die interventionelle Behandlung der MI zugelassen. Seit September 2020 ist zusätzlich das PASCAL Ace®-Implantation-System erhältlich, was eine erweiterte Version des PASCAL®-Systems darstellt. Es ist jedoch noch unbekannt, ob im klinischen Versorgungsalltag eine Reduktion der MI mit gleichzeitiger Verbesserung des funktionellen und hämodynamischen Ergebnisses in gleichem Maße mit dem PASCAL Ace®-Reparatur- System erreicht werden kann. Das Ziel dieser Studie war es daher, die hämodynamischen Effekte sowie das prozedurale und klinische Ergebnis nach kathetergestützter Mitralklappenrekonstruktion mit dem PASCAL Ace®-Mitralklappenreparatur-System zu untersuchen.
Methoden: Die vorliegende Studie war eine retrospektive Single Center Studie, welche konsekutiv 66 Patienten zwischen September 2020 und August 2021 mit symptomatischer hochgradiger MI eingeschlossen hat. Bei diesen Patienten wurde eine Edge- to-Edge Behandlung mit dem PASCAL Ace®-Reparatur-System im Rhön-Klinikum Campus Bad Neustadt durchgeführt. Die Endpunkte unserer Studie folgten den Definitionen des Mitral Valve Academic Research Consortiums. Device success nach 30 Tagen und 5 Monaten wurde definiert als eine persistierende MI ≤ 2, fehlende Mitralklappenstenose, Überleben, fehlender Schlaganfall und fehlende Notwendigkeit für einen erneuten chirurgischen oder interventionellen Eingriff aufgrund eines Deviceversagens. Der primäre Sicherheitsendpunkt wurde definiert als eine Kombination der folgenden schweren unerwünschten Ereignisse (MAE) nach 30 Tagen und 5 Monaten: Gesamtmortalität, Schlaganfall, Herzinfarkt und Neubeginn einer Nierenersatztherapie oder schwere Blutung.
Ergebnisse: Das PASCAL Ace®- Reparatursystem konnte bei 65/66 (98,5%) Patienten erfolgreich implantiert werden. Der Device success mit dem PASCAL Ace® betrug 97%. Bei der Mehrheit der Patienten (66,7%) wurde ein Device implantiert. Bei 21/66 (31,8%) Patienten wurden zwei Devices implantiert. Die mittlere Gesamt-Prozedurzeit betrug 67 ± 32 min. Follow-up Untersuchungen in unserer Klinik erfolgten bei 59/66 (89,4%) Patienten. 3 Patienten starben vor der Nachuntersuchung. Bei 59 Patienten konnte eine signifikante Reduktion des PCWPmean (22 ± 9 mmHg vs. 15 ± 9 mmHg, p=0,001), des PAPsys (49 ± 13 mmHg vs. 40 ± 14 mmHg, p=0,005), des PAPmean (31 ± 10 mmHg vs. 25 ± 10 mmHg, p=0,010) und PAPdias (18 ± 8 mmHg vs. 14 ± 8 mmHg, p=0,006) erreicht werden. Der Herzindex zeigte keine Zunahme (2,0 ± 0,5 vs. 2,1 ± 0,5, p=0,290). Die postprozedurale MI war ≤ 1 bei 82,2% und nach 5 Monaten Follow-up bei 84,7% der Patienten. Die Reduktion der MI führte zu einer relevanten Verbesserung der LVEF (45 ± 17% vs. 51 ± 12%, p=0,048). Der LV-Durchmesser zeigte kein Unterschied (LVEDD 55 ± 7 mm vs. 52 ± 8 mm, p=0,053). Die Schaffung einer doppelten Mitralklappenöffnungsfläche nach Deviceimplantation resultierte bei der Nachuntersuchung nicht in einer relevanten Mitralklappenstenose (mittlerer transmitraler Druckgradient 2,8 ± 0,7 mmHg). Die Funktionsfähigkeit verbesserte sich nach 5 Monaten im Vergleich zum präinterventionellem Zeitpunkt deutlich (86,5% der Patienten befanden sich in der NYHA-Funktionsklasse I oder II, p=0,001). Die zurückgelegte Distanz im 6 – Minuten – Gehtest erhöhte sich durchschnittlich um 79m (p=0,009). Der KCCQ und EQ-5D-5L verbesserten sich um 19 bzw. 18 Punkte (p=0,012; p=0,025). Die mittleren proBNP-Spiegel sanken signifikant von 4832 auf 2137 pg/ml (p=0,003). Der primäre Sicherheitsendpunkt nach 30 Tagen und nach 5 Monaten betrug 4,5% und 4,8%. Ein Patient hatte eine punktionswürdige Perikardtamponade nach dem Eingriff. Schwere Blutungen traten bei 2 Patienten im Bereich der Zugangsstelle auf. Innerhalb der ersten 30 Tage verstarb kein Patient. Nach 5 Monaten starben 3 Patienten (4,8%), keiner von ihnen aufgrund einer Fehlfunktion des Devices.
Schlussfolgerung: Unsere Studie zeigt vielversprechende Ergebnisse in der Reduktion einer MI Grad 3+/4 mit dem neuen Mitralklappen-Reparatursystem PASCAL Ace®. Die Reduktion der MI kann auf diese Art erfolgreich und sicher durchgeführt werden. Dieses Verfahren führt auch im mittelfristigen Verlauf zu einer anhaltenden und effizienten Reduktion der MI, einer Verbesserung der körperlichen Leistungsfähigkeit, der Lebensqualität, des proBNP- Spiegels und der Hämodynamik.Background: Edge-to-edge catheter-based therapy for MR has become a valuable and well-established treatment option in patients with severe MR who are at high surgical risk. In addition to the MitraClip®, the PASCAL® transcatheter valve repair system is approved for the interventional treatment of MR. Since September 2020 the PASCAL Ace® Implantation System, an newer version of the PASCAL® system, is also available. However, evidence is scarce regarding MR reduction and concomitant improvement in functional and hemodynamic outcome using the PASCAL Ace® repair system. The aim of the study was to assess the hemodynamic effects as well as the procedural and clinical outcome after transcatheter mitral valve repair using the PASCAL Ace® mitral valve repair system in a retrospective manner.
Methods: The present study was a retrospective single-center study that consecutively included 66 patients between September 2020 and August 2021 with symptomatic severe MR. The patients underwent edge-to-edge treatment with the PASCAL Ace® repair system at the Rhön-Klinikum Bad Neustadt. The endpoints of our study followed the definitions of the Mitral Valve Academic Research Consortium. Device success at 30 days and 5 months was defined as persistent mitral valve regurgitation ≤ 2, lack of mitral valve stenosis, absence of death, stroke, and freedom of unplanned surgical or interventional procedures related to the device. The primary safety endpoint was defined as a composite of the following major adverse events (MAE) at 30 days and 5 months: all-cause mortality, stroke, myocardial infarction, and new need for renal replacement therapy or major bleeding.
Results: Successful implantation of the PASCAL Ace® repair system was achieved in 65/66 (98.5%) patients. Device success for PASCAL Ace® was high (97%). The majority of patients were treated with one device (66.7%). Two devices were implanted in 21/66 (31.8%) patients. The mean total procedure time was 67 ± 32 min. On-site-follow-up was performed in 59/66 (89.4%) patients. 3 patients died before follow-up. In 59 patients, a significant reduction in PCWPmean (22 ± 9 mmHg vs. 15 ± 9 mmHg, p=0.001), PAPsys (49 ± 13 mmHg vs. 40 ± 14 mmHg, p=0.005), PAPmean (31 ± 10 mmHg vs. 25 ± 10 mmHg, p=0.010) and PAPdias (18 ± 8 mmHg vs. 14 ± 8 mmHg, p=0.006) could be achieved. The cardiac index showed no difference (2.0 ± 0.5 vs. 2.1 ± 0.5, p=0.290). Postprocedural MR was ≤ 1 in 82.2% and at 5 months follow-up in 84.7% of patients. The reduction in MR resulted in a relevant improvement in LVEF (45± 17% vs. 51 ± 12%, p=0.048). The LV diameter showed no difference (LVEDD 55 ± 7 mm vs. 52 ± 8 mm, p=0.053). The creation of a double mitral valve opening area after device implantation did not result in a relevant mitral valve stenosis (mean transmitral pressure gradient 2.8 ± 0.7 mmHg) at the follow-up examination. After successful TEER with PASCAL Ace® a significant improvement of functional capacity could be observed after 5 month (86.5% of the patients were in NYHA functional class I or II, p<0.001). The mean 6-minute walk test increased significantly by 79m (p=0.009). The KCCQ and EQ-5D-5L improved by 19 and 18 points, respectively (p=0.012; p=0.025). Mean proBNP levels decreased significantly from 4832 to 2137 pg/mL (p=0.003). The primary safety endpoints at 30 days and 5 months were 4.5% and 4.8%, respectively. One patient experienced pericardial effusion after the procedure. Major bleeding occurred in 2 patients at the access site. No patient died within the first 30 days. After 5 months, 3 patients (4.8%) died, none of them due to device malfunction.
Conclusions: This study demonstrates promising results with the new PASCAL Ace® mitral valve repair system a newer version of the PASCAL® device in the treatment of patients with at least MR grade 3+ in a real-world setting. MR reduction can be performed successfully and safely resulting in a sustained and efficient MR reduction, improvement of exercise capacity, quality of life, NT- proBNP levels and hemodynamics at 5 month follow-up
Calculating Joint Confidence Bands for Impulse Response Functions using Highest Density Regions
No full textThis paper proposes a new non-parametric method of constructing joint confidence bands for impulse response functions of vector autoregressive models.The estimation uncertainty is captured by means of bootstrapping and the highest density region (HDR) approach is used to construct the bands. A
Monte Carlo comparison of the HDR bands with existing alternatives shows
that the former are competitive with the bootstrap-based Bonferroni and
Wald confidence regions. The relative tightness of the HDR bands matched
with their good coverage properties makes them attractive for applications.
An application to corporate bond spreads for Germany highlights the potential
for empirical work