Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes

Aims  To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). Methods and results  In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting ≥3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean ± standard deviation) were 10 ± 25 (8 mg), 4 ± 10 (16 mg), and 163 ± 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked ∼30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4–11%). Conclusions  Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y12 inhibition sustained for ≥8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable

On potential kernels associated with random dynamical systems

Let $(\Theta;, \phi)$ be a continuous random dynamical system defined on a probability space $(\Omega, F, P)$ and taking values on a locally compact Hausdorff space E. The associated potential kernel V is given by $V f(\omega, x) = \int_0^\infty f (\Theta_t \omega, \phi(t, \omega)x)dt, \omega \in \Omega, x \in E$. In this paper, we prove the equivalence of the following statements: 1. The potential kernel of $(\Theta, \phi)$ is proper, i.e. $V f$ is x-continuous for each bounded, x-continuous function with uniformly random compact support. 2. $(\Theta, \phi)$ has a global Lyapunov function, i.e. a function $L : \Omega \times E \rightarrow (0, \infty)$ which is x-continuous and $L(\Theta_t\omega, \phi(t,\omega)x) \downarrow 0$ as $t \uparrow \infty$. In particular, we provide a constructive method for global Lyapunov functions for gradient-like random dynamical systems. This result generalizes an analogous theorem known for deterministic dynamical systems

Temporal Imaging CeBr3 Compton Camera: A New Concept for Nuclear Decommissioning and Nuclear Waste Management

During nuclear decommissioning or waste management operations, a camera that could make an image of the contamination field and identify and quantify the contaminants would be a great progress. Compton cameras have been proposed, but their limited efficiency for high energy gamma rays and their cost have severely limited their application. Our objective is to promote a Compton camera for the energy range (200 keV – 2 MeV) that uses fast scintillating crystals and a new concept for locating scintillation event: Temporal Imaging. Temporal Imaging uses monolithic plates of fast scintillators and measures photons time of arrival distribution in order to locate each gamma ray with a high precision in space (X,Y,Z), time (T) and energy (E). This provides a native estimation of the depth of interaction (Z) of every detected gamma ray. This also allows a time correction for the propagation time of scintillation photons inside the crystal, therefore resulting in excellent time resolution. The high temporal resolution of the system makes it possible to veto quite efficiently background by using narrow time coincidence (< 300 ps). It is also possible to reconstruct the direction of propagation of the photons inside the detector using timing constraints. The sensitivity of our system is better than 1 nSv/h in a 60 s acquisition with a 22Na source. The project TEMPORAL is funded by the ANDRA/PAI under the grant No. RTSCNADAA160019

Impact on timing and light extraction of a photonic crystal as measured on a half patterned LYSO crystal: implications for time of flight PET imaging

International audienc

First images from a CeBr 3 /LYSO:Ce Temporal Imaging portable Compton camera at 1.3 MeV

International audienceDuring nuclear decommissioning or waste management operations, there is a need for imaging the contamination field while identifying and quantifying the contaminants. Our objective is to test a Compton camera within the energy range 300 keV-2 MeV that uses both light and timing distribution of fast scintillating monolithic crystals. In this experiment we use a 5 mm thick CeBr3 scatterer plate and a 20 mm thick LYSO absorber plate. Our algorithms record for each scintillation event the full position and energy of the event including DOI, even in the thin plate and the relative timing between the detection in the two plate. Our CRT was measured at 293 ps FWHM in coincidence mode without DOI correction. This good time resolution allows for a stringent veto on real Compton event that must be recorded simultaneously in both the scatterer and the absorber plates, thus reducing background very efficiently. Acquisitions were performed with a Phillips Digital Photon Counter SiPM 3200 matrix with a delay-time correction map applied pixel by pixel. After accurate detection of gamma interaction coordinates (x,y,z) and energy in each plate, a list-mode maximum likelihood iterative reconstruction algorithm is applied to better estimate the gamma source activity distribution. Our Compton camera is a promising device for imaging high energy gamma rays, moreover, it can be also suitable for on-line monitoring due to its timing performance. The project TEMPORAL is funded by the ANDRA/PAI under the grant No. RTSCNADAA160019

Temporal Imaging CeBr

During nuclear decommissioning or waste management operations, a camera that could make an image of the contamination field and identify and quantify the contaminants would be a great progress. Compton cameras have been proposed, but their limited efficiency for high energy gamma rays and their cost have severely limited their application. Our objective is to promote a Compton camera for the energy range (200 keV – 2 MeV) that uses fast scintillating crystals and a new concept for locating scintillation event: Temporal Imaging. Temporal Imaging uses monolithic plates of fast scintillators and measures photons time of arrival distribution in order to locate each gamma ray with a high precision in space (X,Y,Z), time (T) and energy (E). This provides a native estimation of the depth of interaction (Z) of every detected gamma ray. This also allows a time correction for the propagation time of scintillation photons inside the crystal, therefore resulting in excellent time resolution. The high temporal resolution of the system makes it possible to veto quite efficiently background by using narrow time coincidence (< 300 ps). It is also possible to reconstruct the direction of propagation of the photons inside the detector using timing constraints. The sensitivity of our system is better than 1 nSv/h in a 60 s acquisition with a 22Na source. The project TEMPORAL is funded by the ANDRA/PAI under the grant No. RTSCNADAA160019

Efficacy and safety of Deferasirox (Exjade) in reducing cardiac iron in patients with \u3b2-Thalassemia major : results from the cardiac substudy of the EPIC trial

50th Annual Meeting of the American-Society-of-Hematology -- DEC 06-09, 2008 -- San Francisco, CAWOS: 000262104704480Amer Soc Hemato