In silico comparison of pharmacokinetic properties of three extended half-life factor IX concentrates

Purpose: Pharmacokinetic (PK) differences between the extended half-life (EHL) factor IX (FIX) concentrates for hemophilia B exist, which may influence hemostatic efficacy of replacement therapy in patients. Therefore, we aimed to evaluate the PK properties of three EHL-FIX concentrates and compare them to a standard half-life (SHL) recombinant FIX (rFIX) concentrate. Methods: Activity-time profiles of PEGylated FIX (N9-GP), FIX linked with human albumin (rIX-FP), FIX coupled to human IgG1 Fc-domain (rFIXFc), and SHL rFIX were simulated for 10,000 patients during steady-state dosing of 40 IU/kg once weekly (EHL-FIX) and biweekly (rFIX) using published concentrate specific population PK models. Results: Half-lives were respectively 80, 104, and 82 h for N9-GP, rIX-FP, and rFIXFc versus 22 h for rFIX. Between the EHL concentrates, exposure was different with area under the curve (AUC) values of 78.5, 49.6, and 12.1 IU/h/mL and time above FIX target values of 0.10 IU/mL of 168, 168, and 36 h for N9-GP, rIX-FP, and rFIXFc, respectively. N9-GP produced the highest median in vivo recovery value (1.70 IU/dL per IU/kg) compared with 1.18, 1.00, and 1.05 IU/dL per IU/kg for rIX-FP, rFIXFc, and rFIX, respectively. Conclusions: When comparing EHL products, not only half-life but also exposure must be considered. In addition, variation in extravascular distribution of the FIX concentrates must be taken into account. This study provides insight into the different PK properties of these concentrates and may aid in determination of dosing regimens of EHL-FIX concentrates in real-life

Open Problems in Extracellular RNA Data Analysis: Insights From an ERCC Online Workshop.

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19-20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop presentations and discussions are available (https://exRNA.org/exRNAdata2021-videos/). There were three target audiences: experimentalists who generate exRNA sequencing data, computational and data scientists who work with those groups to analyze their data, and experimental and data scientists new to the field. Here we summarize issues explored during the workshop, including progress on an effort to develop an exRNA data analysis challenge to engage the community in solving some of these open problems

Open problems in extracellular RNA data analysis : insights from an ERCC online workshop

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19-20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop presentations and discussions are available (https://exRNA.org/exRNAdata2021-video). There were three target audiences: experimentalists who generate exRNA sequencing data, computational and data scientists who work with those groups to analyze their data, and experimental and data scientists new to the field. Here we summarize issues explored during the workshop, including progress on an effort to develop an exRNA data analysis challenge to engage the community in solving some of these open problems

Reconstruction of the decay B"-#->#D_1"o(2414)#pi#"-

We present the results of a partial reconstruction of the decay channel B"-#->#D_J"("*")"0#pi#"- performed using the ARGUS detector operating at the e"+e"- storage-ring DORIS II. In the context of this paper, D_J"("*")"0 is an L=1 excited charm meson decaying to D"*"+#pi#"-. The measured product of branching ratios is Br(B"-#->#D_1"0(2414)#pi#"-).Br((D_1"0#->#D"*"+#pi#"-)=(0.17#+-#0.05#+-#0.04)% where the first error is statistical and the second systematic. No evidence for the decay B"-#->#D_2"*"0(2459)#pi#"- is observed. We calculate the upper limit Br(B"-#->#D_2"*"0(2459)#pi#"-).Br(D_2"*"0#->#D"*"+#pi#"-)<0.07% at the 90% confidence level. (orig.)SIGLEAvailable from TIB Hannover: RA 2999(94-069) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Searching for very-high-energy electromagnetic counterparts to gravitational-wave events with the Cherenkov Telescope Array

The detection of electromagnetic (EM) emission following the gravitational wave (GW) event GW170817 opened the era of multi-messenger astronomy with GWs and provided the first direct evidence that at least a fraction of binary neutron star (BNS) mergers are progenitors of short Gamma-Ray Bursts (GRBs). GRBs are also expected to emit very-high energy (VHE, > 100 GeV) photons, as proven by the recent MAGIC and H.E.S.S. observations. One of the challenges for future multi-messenger observations will be the detection of such VHE emission from GRBs in association with GWs. In the next years, the Cherenkov Telescope Array (CTA) will be a key instrument for the EM follow-up of GW events in the VHE range, owing to its unprecedented sensitivity, rapid response, and capability to monitor a large sky area via scan-mode operation. We present the CTA GW follow-up program, with a focus on the searches for short GRBs possibly associated with BNS mergers. We investigate the possible observational strategies and we outline the prospects for the detection of VHE EM counterparts to transient GW events

Monte Carlo Simulations and Validation of NectarCAM, a Medium Sized Telescope Camera for CTA

The upcoming Cherenkov Telescope Array (CTA) ground-based gamma-ray observatory will open up our view of the very high energy Universe, offering an improvement in sensitivity of 5-10 times that of previous experiments. NectarCAM is one of the proposed cameras for the Medium-Sized Telescopes (MST) which have been designed to cover the core energy range of CTA, from 100 GeV to 10 TeV. The final camera will be capable of GHz sampling and provide a field of view of 8 degrees with its 265 modules of 7 photomultiplier each (for a total of 1855 pixels). In order to validate the performance of NectarCAM, a partially-equipped prototype has been constructed consisting of only the inner 61-modules. It has so far undergone testing at the integration test-bench facility in CEA Paris-Saclay (France) and on a prototype of the MST structure in Adlershof (Germany). To characterize the performance of the prototype, Monte Carlo simulations were conducted using a detailed model of the 61 module camera in the CORSIKA/sim_telarray framework. This contribution provides an overview of this work including the comparison of trigger and readout performance on test-bench data and trigger and image parameterization performance during on-sky measurements

Sensitivity of CTA to gamma-ray emission from the Perseus galaxy cluster

In these proceedings we summarize the current status of the study of the sensitivity of the Cherenkov Telescope Array (CTA) to detect diffuse gamma-ray emission from the Perseus galaxy cluster. Gamma-ray emission is expected in galaxy clusters both from interactions of cosmic rays (CR) with the intra-cluster medium, or as a product of annihilation or decay of dark matter (DM) particles in case they are weakly interactive massive particles (WIMPs). The observation of Perseus constitutes one of the Key Science Projects to be carried out by the CTA Consortium. In this contribution, we focus on the DM-induced component of the flux. Our DM modelling includes the substructures we expect in the main halo which will boost the annihilation signal significantly. We adopt an ON/OFF observation strategy and simulate the expected gamma-ray signals. Finally we compute the expected CTA sensitivity using a likelihood maximization analysis including the most recent CTA instrument response functions. In absence of signal, we show that CTA will allow us to provide stringent and competitive constraints on TeV DM, especially for the case of DM decay