Optimization and validation of automated hippocampal subfield segmentation across the lifespan

Automated segmentation of hippocampal (HC) subfields from magnetic resonance imaging (MRI) is gaining popularity, but automated procedures that afford high speed and reproducibility have yet to be extensively validated against the standard, manual morphometry. We evaluated the concurrent validity of an automated method for hippocampal subfields segmentation (automated segmentation of hippocampal subfields, ASHS; Yushkevich et al.,2015b) using a customized atlas of the HC body, with manual morphometry as a standard. We built a series of customized atlases comprising the entorhinal cortex (ERC) and subfields of the HC body from manually segmented images, and evaluated the correspondence of automated segmentations with manual morphometry. In samples with age ranges of 6–24 and 62–79 years, 20 participants each, we obtained validity coefficients (intraclass correlations, ICC) and spatial overlap measures (dice similarity coefficient) that varied substantially across subfields. Anterior and posterior HC body evidenced the greatest discrepancies between automated and manual segmentations. Adding anterior and posterior slices for atlas creation and truncating automated output to the ranges manually defined by multiple neuroanatomical landmarks substantially improved the validity of automated segmentation, yielding ICC above 0.90 for all subfields and alleviating systematic bias. We cross-validated the developed atlas on an independent sample of 30 healthy adults (age 31–84) and obtained good to excellent agreement: ICC (2) = 0.70–0.92. Thus, with described customization steps implemented by experts trained in MRI neuroanatomy, ASHS shows excellent concurrent validity, and can become a promising method for studying age-related changes in HC subfield volumes

Gradient-flow scale setting with Nf=2+1+1N_f=2+1+1 Wilson-clover twisted-mass fermions

We present a determination of the gradient flow scales w0 , t0‾‾√ and t0/w0 in isosymmetric QCD, making use of the gauge ensembles produced by the Extended Twisted Mass Collaboration (ETMC) with Nf=2+1+1 flavours of Wilson-clover twisted-mass quarks including configurations close to the physical point for all dynamical flavours. The simulations are carried out at three values of the lattice spacing and the scale is set through the PDG value of the pion decay constant, yielding w0=0.17383(63) fm, t0‾‾√=0.14436(61) fm and t0/w0=0.11969(62) fm. Finally, fixing the kaon mass to its isosymmetric value, we determine the ratio of the kaon and pion leptonic decay constants to be fK/fπ=1.1995(44)

Quark and Gluon Momentum Fractions in the Pion from N f = 2 + 1 + 1 Lattice QCD

We perform the first full decomposition of the pion momentum into its gluon and quark contributions. We employ an ensemble generated by the Extended Twisted Mass Collaboration with Nf = 2 + 1 + 1 Wilson twisted mass clover fermions at maximal twist tuned to reproduce the physical pion mass. We present our results in the MS scheme at 2 GeV. We find (x)u+d = 0.601 (28), (x)s = 0.059 (13), (x)c = 0.019 (05), and (x)g =0.52 (11) for the separate contributions, respectively, whose sum saturates the momentum sum rule

Nutzung von Registerdaten für regulatorische Entscheidungsfindung

Über die vergangenen Jahre hat die Nutzung von Registerdaten für die Arzneimittelforschung vermehrt an Bedeutung gewonnen. Folglich griffen im Jahr 2020 die Europäische Arzneimittelagentur (European Medicines Agency, EMA) und Vertreter der nationalen Zulassungsbehörden (Heads of Medicines Agencies, HMA) dies als Teil ihrer Netzwerkstrategie zum verbesserten Schutz der öffentlichen Gesundheit auf. Registerdaten gehören zu den sogenannten Real World Data (RWD) und können zur Beantwortung von Fragen zur Arzneimittelsicherheit und zur Untersuchung der Wirksamkeit von Arzneimitteln herangezogen werden. Registerdaten finden zum Beispiel Anwendung bei Studien zu Arzneimitteln für seltene Krankheiten und bei Studien zu speziellen Patientenpopulationen wie der Arzneimittelexposition bei Schwangeren. Bei der Durchführung von registerbasierten Studien stellen sich vielfältige Fragen, die u.a. das Auffinden geeigneter Datenquellen, die Nutzung bestehender Register oder die Etablierung neuer Register betreffen. Dieser Beitrag gibt eine Übersicht über aktuelle Initiativen zur Verbesserung der Nutzung von Registerdaten für regulatorische Zwecke auf europäischer und nationaler Ebene

Instruments of official communication by regulatory authorities on risks of drug use

Active communication of authorities, such as the Federal Institute for Drugs and Medical Devices (BfArM) and the Paul Ehrlich Institute (PEI), including maintenance of contacts with health care professionals, as well as press and public relations work, are essential prerequisites for ensuring that information on the risks of using medicinal products reaches both affected patients and healthcare professionals quickly and in a targeted manner. The various instruments of targeted communication describe possible risks and also contain recommendations that help to reduce the risk of using a medicinal product. The supplementary public relations work aims to make the tasks and objectives of the authority known to the public and to experts with the goal of creating and expanding trust in the actions of the authorities. To this end, appropriate communication platforms must be established and accepted so that they are used by both experts and the general public and the authority is perceived and appreciated as a reliable source of risk information. The currently available instruments of targeted risk communication, such as Dear Health Care Professional Communication (DHPC), risk management plans, and educational materials are described in this paper as well as broader communication on official websites or towards the media. Finally, PEI’s risk communication is highlighted with particular reference to COVID-19 vaccines.Die aktive Kommunikation von Behörden, wie dem Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) und dem Paul-Ehrlich-Institut (PEI), einschließlich der Kontaktpflege zu Fachkreisen sowie Presse- und Öffentlichkeitsarbeit sind wesentliche Voraussetzung dafür, dass Informationen zu Anwendungsrisiken von Arzneimitteln sowohl betroffene Patientinnen und Patienten als auch Angehörige der Heilberufe schnell und gezielt erreichen. Die verschiedenen Instrumente der gezielten Kommunikation beschreiben mögliche Risiken und enthalten darüber hinaus auch Empfehlungen, die helfen, das Anwendungsrisiko eines Arzneimittels zu reduzieren. Die ergänzende Öffentlichkeitsarbeit zielt darauf ab, die Aufgaben und Ziele der Behörde in der Bevölkerung und in Fachkreisen bekannt zu machen, um Vertrauen in behördliches Handeln zu schaffen und auszubauen. Dafür müssen entsprechende Kommunikationsplattformen etabliert und akzeptiert sein, die sowohl von Fachkreisen als auch von der Bevölkerung genutzt werden können. Die aktuell verfügbaren Instrumente der gezielten Risikokommunikation, wie Rote-Hand-Briefe (RHB), Risikomanagementpläne und Schulungsmaterial, werden in dieser Publikation ebenso beschrieben wie die breiter angelegte Kommunikation auf den behördlichen Webseiten oder gegenüber den Medien. Schließlich wird die Risikokommunikation des PEI unter besonderer Berücksichtigung der COVID-19-Impfstoffe beleuchtet

Quark and Gluon Momentum Fractions in the Pion from Nf=2+1+1N_f=2+1+1 Lattice QCD

We perform the first full decomposition of the pion momentum into its gluon and quark contributions. We employ an ensemble generated by the Extended Twisted Mass Collaboration with $N_f=2+1+1$ Wilson twisted mass clover fermions at maximal twist tuned to reproduce the physical pion mass. We present our results in the $\overline{MS}$ scheme at 2 GeV. We find $⟨x⟩_{u+d}=0.601(28), ⟨x⟩_s=0.059(13), ⟨x⟩_c=0.019(05)$, and $⟨x⟩_g=0.52(11)$ for the separate contributions, respectively, whose sum saturates the momentum sum rule

Pion-pole contribution to HLbL from twisted mass lattice QCD at the physical point

We report on our computation of the pion transition form factor ${\cal F}_{P\rightarrow \gamma^*\gamma^*}$ from twisted mass lattice QCD in order to determine the numerically dominant light pseudoscalar pole contribution in the hadronic light-by-light scattering contribution to the anomalous magnetic moment of the muon $a_\mu =(g-2)_\mu$. The pion transition form factor is computed directly at the physical point. We present first results for our estimate of the pion-pole contribution with kinematic setup for the pion at rest.Comment: 9 pages, 7 figures; Proceedings of the 38th International Symposium on Lattice Field Theory - Lattice 2021, Zoom/Gather@Massachusetts Institute of Technolog

Pion-pole contribution to HLbL from twisted mass lattice QCD at the physical point

We report on our computation of the pion transition form factor ${\cal F}_{P\rightarrow \gamma^*\gamma^*}$ from twisted mass lattice QCD in order to determine the numerically dominant light pseudoscalar pole contribution in the hadronic light-by-light scattering contribution to the anomalous magnetic moment of the muon $a_\mu =(g-2)_\mu$. The pion transition form factor is computed directly at the physical point. We present first results for our estimate of the pion-pole contribution with kinematic setup for the pion at rest