BD Technologie (United States)

In silico modeling of subcutaneous injections is a promising tool to derisk and optimize the development of injections systems and improve preliminary understanding of the injectability of drugs. Such modeling can be leveraged early in development, prior to pre-clinical studies, to reduce testing burden and effectively predict aspects such as the time and forces required for full dose delivery into tissue and the tissue-injectate-device interactions. In this work, we address the three main in silico pillars (primary container, injection device, and tissue) that are necessary to simulate a parenteral injection. We showcase how their modeling can be combined and applied to various delivery systems and injection conditions to enable appropriate systems and parameters selection to achieve desired performance. Case studies of viscous drugs in PFS/AI and wearable injection systems with non-rigid component properties are presented to highlight the theoretical treatment of interfaces, the critical inputs required to achieve accurate predictions, the insights gained, and the good agreement between model predictions and experimental results.

<ns3:p>The 25th annual Bioinformatics Open Source Conference (BOSC 2024, open-bio.org/events/bosc-2024) was part of the 2024 conference on Intelligent Systems for Molecular Biology (ISMB 2024). Launched in 2000 and held yearly since, BOSC is the premier meeting covering open-source bioinformatics and open science. ISMB 2024 was held in Montréal, Canada, with an online participation option. A total of nearly 2000 people attended; about 200 people participated in BOSC sessions. Over the course of two days, BOSC covered a wide range of topics in open science and open source bioinformatics, including Data Analysis, Open Data, Visualization, Developer Tools and Libraries, Standards and Frameworks for Open Science, and Open AI/ML. Mélanie Courtot delivered an impactful first keynote with a perspective on how “The Data Shows We Need Better Data”. The second keynote speaker, Andrew Su, discussed “Open Data, Knowledge Graphs, and Large Language Models.” BOSC ended with a panel, “Open Source AI/ML: A Game Changer for Bioinformatics?,” in which Lawrence Hunter and Thomas Hervé Mboa Nkoudou joined BOSC’s keynote speakers as panelists. Immediately following BOSC, the CollaborationFest was held at Montréal’s University of Québec campus. First launched in 2010, CoFest is a collaborative work event held yearly around BOSC. This year’s CoFest included 42 participants who worked together on 10 projects.</ns3:p>

Die Erforschung der ereignisreichen Geschichte des 20. Jahrhunderts ist nur schwer ohne eine Analyse der tiefer liegenden Prozesse des Zusammenspiels der ethnosozialen Faktoren vorstellbar, die großen Einfluss auf den Weg der Völker und Staaten im vergangenen Jahrhundert hatten. Aus diesem Blickwinkel richten die Forscher ihr Augenmerk weiterhin auf Genesis und Evolution der Wahrnehmung anderer Zivilisationen und Gesellschaften, besonders in Zeiten historischer Umbrüche. Solch ein Zeitraum war der Erste Weltkrieg, den die Zeitgenossen als den Großen Krieg bezeichneten. Die vorliegende Untersuchung widmet sich einigen Aspekten der Wahrnehmung Deutschlands und der Deutschen in Russland in der Zeit 1914-1918. Dabei liegt die zeitliche Obergrenze hier nicht im März 1918, als die bolschewistische Regierung mit den Staaten des Vierbundes den "Raubfrieden" von Brest-Litowsk unterzeichnete, sondern es wird auch der Zeitraum Frühjahr/Herbst 1918 bis zur Einstellung der Kampfhandlungen an der Westfront behandelt. Die Arbeiten heutiger Historiker zeigen, dass die Wahrnehmung einer Gesellschaft durch eine andere in der Regel durch eine Mischung aus politischen, soziokulturellen und wirtschaftlichen Faktoren unterschiedlicher Ausrichtung bedingt war. Doch verschob sich diese Wahrnehmung immer dann in den Bereich der negativen Reflexion, wenn es eine bewaffnete Konfrontation gab, deren Dauer und Härte, wie der Erste Weltkrieg zeigt, sich direkt proportional auf die Intensität der Ablehnung all dessen auswirkte, was die jeweilige Gesellschaft mit dem Feind assoziierte.¹ Die Ereignisse, die von einer Verbreitung antideutscher Stimmungen bei "Eliten" und "Fußvolk" des Russischen Reiches zeugten, wurden in Monografien, Artikeln und Dissertationen sowohl ausländischer -vor allem deutscher -als auch einheimischer Wissenschaftler dargestellt.²

The impingement zone created by the impingement of two free, thin sheets of liquids was studied using photographic techniques. The experimental parameters studied were the impingement angle, single-sheet velocity, single-sheet thickness at impingement, liquid surface tension, and liquid viscosity. Momentum balances of the impingement are in good agreement with observations that a critical mixed sheet velocity must be achieved in order for the liquid to flow in the backward direction of the mixed sheet. The critical mixed sheet velocity for backflow was found to correlate well with the Taylor–Culick velocity. However, if all of the kinetic energy associated with the single-sheet component velocity that is destroyed upon impingement is dissipated into the mixed sheet, then that critical velocity cannot be achieved, and there will be no backflow from the backward part of the mixed sheet. An unusual result of the study is that the projection of the single sheets onto the mixed sheet at impingement presents as a “skin” that can be clearly seen in photographs or a video. This “skin” feature potentially allows for the use of macro photography to measure the thickness of the single sheet at impingement.

Limited published data exists quantifying the influence of human factors (HF) and pen needle (PN) design on delivery outcomes of pen injection systems. This preclinical in vivo study examines the impact of PN hub design and applied force against the skin during injection on needle penetration depth (NPD). To precisely locate injection depth, PN injections (20 µl; 2 IU, U-100 volume equivalent) of iodinated contrast agent were administered to the flank of Yorkshire swine across a range of clinically relevant application forces against the skin (0.25, 0.75, 1.25, and 2.0 lbf). The NPD, representing in vivo needle tip depth in SC tissue, from four 32 G × 4 mm PN devices (BD Nano™ 2nd Gen and three commercial posted-hub PN devices; n = 75/device/force, 1200 total) was measured by fluoroscopic imaging of the resulting depot. The reengineered hub design more closely achieved the 4 mm target NPD with significantly less variability ( P = .006) than commercial posted-hub PN devices across the range of applied injection forces. Calculations of IM (intramuscular) injection risk completed through in silico probability model, using NPD and average human tissue thickness measurements, displayed a commensurate reduction (~2-8x) compared to conventional PN hub designs. Quantifiable differences in injection depth were observed between identical labeled length PN devices indicating that hub design features, coupled with aspects of variable injection technique, may influence injection depth accuracy and consistency. The reengineered hub design may reduce the impact of unintended individual technique differences by improving target injection depth consistency and reducing IM injection potential.

Abstract The heterogeneous nature of solid tumors, coupled with the relatively small sample size of available biopsies, has led to an emerging need to glean as much information as possible from these valuable specimens. Current approaches to solid tumor analysis fail to completely reveal the diverse range of cellular compartments that comprise the tumor microenvironment. A comprehensive approach to tumor interrogation requires efficient tissue dissociation to facilitate analysis at the single-cell level. In contrast to current methods, single-cell analysis of tumor derived cell suspensions by flow cytometry has the potential to provide a more complete understanding of the many subpopulations within the tumor microenvironment and the cell to cell interactions that govern this space. In order to prepare a cell suspension from solid tumor tissue, most investigators subject the tumor sample to a combination of mechanical and enzymatic dissociation modalities. Regardless of the combination of enzymes used for dissociation, there exists a degree of non-specific proteolytic cleavage. In the work presented here, we set out to quantify the non-specific cleavage associated with a proprietary enzyme mixture developed for tumor dissociation. Using a mixed sample that included peripheral blood mononuclear cells and several cell lines, we were able to generate a sample that expressed approximately 90% of our current antibody catalog. By staining our sample with a rudimentary 3 color panel, we were able to identify 10 individual cell populations based on marker expression and/or scatter. This composite sample was left untreated or exposed to our propriety mixture of dissociation enzymes and then subsequently screened for all 251 antigens in our catalog. The impact of non-specific proteolytic cleavage on surface marker detection was gauged in terms of median fluorescence intensity of positive population and stain index. Our results indicate that of the 251 surface markers tested in our experimental series, less than 10 percent were significantly affected by enzymatic digestion. Of those markers that were affected only a fraction of them were affected to such an extent that it was impossible to detect positive expression. These results underscore the importance of understanding the factors that can influence surface marker detection and bolster our confidence that this particular mixture of enzymes is imparting minimal impact on surface marker detection. Citation Format: Aaron J. Middlebrook, Caitlin Austin, Daniel Santos, Eileen Snowden, Warren Porter, Friedrich Hahn, Mitchell Ferguson, Rainer Blaesius, Smita Ghanekar. The effects of enzymatic digestion on epitope detection by flow cytometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2113.

ObjectiveThe Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbreed Wistar rat strain widely used as a model of genetic generalised epilepsy with absence seizures. As in humans, the genetic architecture that results in genetic generalized epilepsy in GAERS is poorly understood. Here we present the strain-specific variants found among the epileptic GAERS and their related Non-Epileptic Control (NEC) strain. The GAERS and NEC represent a powerful opportunity to identify neurobiological factors that are associated with the genetic generalised epilepsy phenotype.MethodsWe performed whole genome sequencing on adult epileptic GAERS and adult NEC rats, a strain derived from the same original Wistar colony. We also generated whole genome sequencing on four double-crossed (GAERS with NEC) F2 selected for high-seizing (n = 2) and non-seizing (n = 2) phenotypes.ResultsSpecific to the GAERS genome, we identified 1.12 million single nucleotide variants, 296.5K short insertion-deletions, and 354 putative copy number variants that result in complete or partial loss/duplication of 41 genes. Of the GAERS-specific variants that met high quality criteria, 25 are annotated as stop codon gain/loss, 56 as putative essential splice sites, and 56 indels are predicted to result in a frameshift. Subsequent screening against the two F2 progeny sequenced for having the highest and two F2 progeny for having the lowest seizure burden identified only the selected Cacna1h GAERS-private protein-coding variant as exclusively co-segregating with the two high-seizing F2 rats.SignificanceThis study highlights an approach for using whole genome sequencing to narrow down to a manageable candidate list of genetic variants in a complex genetic epilepsy animal model, and suggests utility of this sequencing design to investigate other spontaneously occurring animal models of human disease.