Decolonizing Time, Knowledge, and Disability on the Tenure Clock

We consider the tenure clock's enmeshment in the neoliberal academy's settler colonial and ableist modes of organizing labor and valuing knowledge, modes in turn informed by heteropatriarchal spatiotemporal logics. The tenure clock in the settler academy relies on labor performed by those positioned outside of its time—such as those in temporary or semi-temporary positions, staff, graduate students, and undergraduate students. Our motivation in tracing these logics and formulating feminist strategies to undo them stems directly from observing "faculty with disabilities" at our university struggling against the tenure clock;as well as seemingly abled women faculty, faculty of color, and contingent faculty, who have strained against the academic clock and ended up debilitated in the process. We articulate ways in which more collaborative understandings of university culture and knowledge production might serve to challenge the peculiar temporalities produced by the tenure clock. Listening and learning at the intersections of feminist, Indigenous, and disability studies scholarship teaches us to work toward imagining a different approach to tenure, and from there, the way to a different academy.

Optimized nanoparticle-mediated base editing of cystic fibrosis-causing variants

Background: Next-generation SARS-CoV-2 vaccines demonstrated that nanoparticle messenger ribonucleic acid (mRNA) delivery is effective and safe for in vivo delivery in humans. Current treatments for cystic fibrosis (CF) primarily focus on modulator drug therapies designed to correct malfunctioning CF transmembrane conductance regulator (CFTR) protein, but these modulators are ineffective for the 10% of people with CF with variants that do not allow protein production. Among these is the splice variant 3120 + 1G >A, the most common CF-causing mutation in native Africans. Gene editing would allow production of CFTR protein and enhancement of function using available CFTR modulators. We have demonstrated that electroporation of a modified CRISPR-Cas9 base editor to primary human bronchial epithelial cells carrying 3120 + 1G >A and F508del mutant alleles achieved 75% genome editing of the splice variant, resulting in approximately 40% wild-type (WT) CFTR function [1]. Here,we evaluate the effectiveness of several new nanoparticle formulations at delivering green fluorescent protein (GFP) mRNA to CF bronchial epithelial (CFBE41o-) cells. Using the optimal formulation,we then tested the efficacy correction of the 3120 + 1G >Avariant in a CFTR expression minigene (EMG) integrated into the genome of isogenic CFBE cells using mRNA and plasmid deoxyribonucleic acid (DNA) encoding adenine base editor (ABE) and guide (g)RNA. Method(s): GFP served as a reporter to evaluate transfection efficiency, cell viability, and mean fluorescence intensity (MFI) for three dosages (150, 75, 32.5 ng of mRNA), four polymer-to-mRNA to weight (w/w) ratios (60, 40, 30, 20), and four polymers (R, Y, G, B). 7-AAD served as a live/dead stain to quantify viability, with flow cytometry results analyzed using FlowJo software. CFBE cells stably expressing the 3120 + 1G >A EMG were transfected with the optimized nanoparticle formulation to deliver ABE and gRNA at two dosages (150, 75 ng) of mRNA and DNA. CFTR function in CFBE cellswas measured by short circuit current, forskolin stimulation, and inh-172 inhibition as a measure of editing efficiency. Result(s): Flow cytometry showed that polymer R achieved more than 85% GFP transfection, compared with a maximum of approximately 35% for the other three polymers at the maximum 150-ng dose, with approximately 80% viability normalized to untreated cells. In addition, polymer R achieved GFP MFI more than one order of magnitude as high as other formulations (~30 000 vs 2700 MFI) for the other three polymers at 150-ng dose and 40 w/w ratio. CFBE cells transfected with polymer R nanoparticles containing ABE and guide RNA at 75 ng and 150 ng showed mean CFTR function increase to 10 muA 6 (standard error of the mean [SEM] 1.1 muA) (~10% of WT) and 6.3 muA (SEM 0.9 muA) (~6% of WT), respectively. Greater toxicity at the higher dose could explain the larger increase in CFTR current at the lower dose. DNA-encoded ABE plasmid and gRNA showed a less robust increase in CFTR function (2.9 muA [SEM 0.4 muA] for 75-ng dose;3.0 muA [SEM 0.4 muA] for 150-ng dose), which was probably a result of the nanoparticle formulation being optimized for RNA instead of DNA cargo or the additional intracellular barriers that must be overcome for successful DNA delivery. Conclusion(s): We demonstrated that an optimized nanoparticle formulation containing ABE and gRNA can correct splicing of isogenic cells bearing the 3120 + 1G >A CFTR variant, resulting in recovery of CFTR function. In ongoing work, we are adapting these nanoparticles for RNA- and DNAencoded ABE and gRNA delivery to primary human bronchial epithelial cells.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Optimizing the Interdisciplinary Design of Adaptive Platform Trials

Adaptive platform trials (APTs) are often complex clinical trials that, ideally, are well suited to answer the motivating clinical questions effectively and efficiently, with the motivating clinical questions and associated treatment arms expected to evolve over time as evidence accumulates. Recently, APTs have played a pivotal role in informing public health policy by efficiently generating compelling evidence regarding the effectiveness of therapies for COVID-19. For APTs to be maximally effective in informing future public health policy, they must be carefully tailored to address the right clinical questions, with the right balance of size, scope, rigor, and flexibility. The design process requires input from clinical and statistical domain experts and often includes input from trial implementation personnel, ethicists, and patient representatives. The design process is inherently iterative, with proposed designs evaluated through trial simulation, the identification of strengths and weaknesses of the proposed design, and revision by the team to address weaknesses. This iterative design process requires effective communication and collaboration between the statistical and clinical domain experts. This session is intended to present a current best practice in facilitating and enhancing the collaborative design process for APTs, including how best to present simulation-based trial performance to the design team and ensure effective interdisciplinary communication. The speakers have extensive experience in leading the design of APTs across multiple therapeutic areas, in both academic and industry settings. The session will begin with a brief presentation by Dr. Lewis on the basic structure of an APT and the tasks and challenges associated with the multidisciplinary design process. The subsequent discussion will be organized by the following themes: (1) considerations in the selection of the study population and primary outcome metric;(2) selecting treatment domains and factors to be compared;(3) trial simulation and communication of performance metrics to both statistical and non-statistical team members;and (4) defining and calibrating interim decision rules. Each of the 4 panel members will outline a recommended approach to facilitating 1 of the 4 design tasks, with examples drawn from their experience. The remaining time (15 min) will be available for a panel question-and-answer period. At the end of the session, the audience will have an understanding of the general organization of, and a process for facilitating, the design process for an adaptive platform trial. Panel Members Roger J Lewis, MD, PhD, is a Senior Physician in the Los Angeles County Department of Health Services, Professor of Emergency Medicine at the David Geffen School of Medicine at UCLA, and the Senior Medical Scientist at Berry Consultants, LLC, a group that specializes in innovative clinical trial design. He is also the former Chair of the Department of Emergency Medicine at Harbor-UCLA Medical Center. Dr. Lewis' expertise centers on adaptive and Bayesian clinical trials, including platform trials;translational, clinical, health services and outcomes research methodology;data and safety monitoring boards, and the oversight of clinical trials. Dr. Lewis was elected to membership in the National Academy of Medicine in 2009. He has authored or coauthored over 270 original research publications, reviews, editorials, and chapters. Dr. Lewis is a Past President of the Society for Academic Emergency Medicine (SAEM) and served on the Board of Directors for the Society for Clinical Trials. He is a fellow of the American College of Emergency Physicians, the American Statistical Association, and the Society for Clinical Trials. Juliana Tolles, MD, MHS, is an Assistant Professor of Emergency Medicine at the Harbor-UCLA Medical Center and the David Geffen School of Medicine at UCLA, and a Medical and Statistical Scientist at Berry Consultants, LLC. Her academic research interests include emergency medical services, resuscitation medicine, and trau a care. She has authored several reviews for Journal of the American Medical Association (JAMA) on statistical methodology and has lectured nationally on research methodology for the Society for Academic Emergency Medicine Advanced Research Methodology Evaluation and Design (ARMED) course. She is also a co-investigator for the Strategies to Innovate Emergency Clinical Care Trials (SIREN) network Southern California site. Kert Viele, PhD, is a Director and Senior Statistical Scientist with Berry Consultants, where he leads Berry Consultants' research enterprise. He is a leader in clinical trial implementation of Bayesian hierarchical modeling, with expertise in platform and basket trials as well as clinical trials incorporating the use of historical information. Prior to joining Berry Consultants in 2010, he was a faculty member at the University of Kentucky, where he received the Provost's Award for Outstanding Teaching and was an investigator for NSF and NIH-funded research. He has developed over 100 custom Bayesian adaptive clinical trials for clients in industry, government, and academia, and currently serves on several data safety monitoring boards for randomized clinical trials. A former editor of the journal Bayesian Analysis, Dr. Viele is also an author of FACTS (Fixed and Adaptive Clinical Trial Simulator), clinical trial simulation software currently licensed to multiple pharmaceutical, academic, and government organizations. William Meurer, MD, MS, is an Associate Professor of Emergency Medicine and Neurology at the University of Michigan Health System. In addition, he serves as a Medical and Statistical Scientist for Berry Consultants, LLC. He works to improve the care of patients with acute neurological disease both through his work on the acute stroke team and as a researcher. His work in the field focuses on the design of clinical trials with adaptive and flexible components. In addition, he is a principal investigator of the National Institutes of Neurological Disorders and Stroke (NINDS) Clinical Trials Methodology Course (http:// neurotrials.training) and a co-investigator in the clinical coordinating center of the Strategies to Innovate Emergency Care Clinical Trials (SIREN) network- also funded by NIH). He was a co-investigator on the Adaptive Designs Accelerating Promising Treatments into Trials (ADAPT-IT) project, as part of the FDA Advancing Regulatory Science initiative with NIH.

SITUATED COGNITION 360degree EDITOR 2021: A SOLUTION FOR INTERACTIVE MEDICAL TRAINING DURING THE COVID-19 PANDEMIC PERIOD

Imagine entering an operating theatre or developing clinical skills in empathy and communication through Virtual Reality. To enhance the experience of learning novel methods using VR have been researched and simulated for clinicians. This is because some aspects of clinical training, like conducting procedures and effective team communication focus on 'learning by doing' which is difficult to recreate remotely. Here we present a proof-of-concept prototype of a 360degree-video editor that augments 360degree videos with media to create a mixed reality learning experience. Method An editor was built inside Unity to augment 360degree- videos of real-world scenarios in healthcare with interactive data. Unity is a cross-platform games engine used to create two-dimension three-dimension virtual reality and augmented reality games as well as video players to play panoramic 360degree-videos. The video player is attached to a Render Texture and a Skybox material that provides the spherical surface for the 360degree-video achieving an immersive experience. Results The editor comprises two software packages one for the trainer another for the learner. As a unique feature we introduce clickable Hotspots. This enables users to annotate the 360degree film by tagging specific artefacts in the environment and create a place-based interaction. These Hotspots are anchored to a position and can display text and images and form part of a novel branched timeline of nested data. The intention being the trainer would create the film and annotate the environment with interactive media. This would then be available to the learner who would use the player to view a bespoke teaching package. Conclusion Situated Cognition 360 Editor 2021 envisages trainers creating interactive 360degree-video learning experiences using real life scenarios in healthcare. Future steps involve user experience evaluations co-design and development of new learner interactions that deliver low cost remote and easily deployed healthcare education through immersive learning environments.

Visual Description of Digital IT Consulting Services Using DITCOS-DN: Proposal and Evaluation of a Graphical Editor

The digital transformation of the IT consulting domain recently gained momentum due to the Covid-19 pandemic. However, the range of IT consulting services that are fully digital is still very limited. Plus, there are no standardized and established methods for describing digital IT consulting services, nor there is any suitable tooling for digital IT consulting service provisioning. The present work aims to reduce this gap by contributing to establishing a well-defined approach to formally describing digital IT consulting services that could possibly be a candidate for standardization. Building upon (i) the ontology DITCOS-O, which provides the semantic basis for our approach, and (ii) the YAML-based description notation DITCOS-DN, which we leverage to describe digital IT consulting service models, we propose a graphical, web-based editor (called DITCOS-ModEd) to simplify service model maintenance. Following a design science based research process, we developed a prototype and empirically evaluated its applicability with the help of IT consultants. This first evaluation allowed us to identify some limitations and to plan specific improvements, both to the underlying artifacts DITCOS-O and DITCOS-DN, as well as to DITCOS-ModEd itself. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Interstitial Lung Diseases Virtual Clinics: a novel medicaleducation method during pandemic times

Introduction: SARS-COV-2 pandemic challenged the medical education face-to-face meetings. ILD Virtual Clinics(ILD-VC) were thought as a non-traditional medical education model to address topics about a holistic managementof ILDs. Weekly videoconferencing interviews with local experts and Q&A from the public were developed. Objective(s): To describe a virtual medical education model with an innovative format through interviews with experts indifferent ILD topics as a best practice.Implementation: 20 episodes of ILD-VC were carried out with an audience of pulmonologists, rheumatologists andgeneral physicians from Argentina, Paraguay and Uruguay. Each 60 minutes duration episode with the presence ofthe coordinators and an expert in a specific topic for each episode recognized as an unmet need. The main objectivewas to discuss ILD management from different points of view and create a digital library with advices from thechosen experts. Some of the topics were: antigen searching for HP;determining progression in PF-ILDs;amongothers. The number of virtual assistants was 217 per episode (average) with a maximum of 382 and more de 4300connections in total. A third season in planned for 2022. Conclusion(s): This innovate format provided a better understanding of ILD holistic management. Disclosures: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment related to the development of the abstract. Boehringer Ingelheim (BI) was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. The study was supported and funded by BI.

BJPsych Open: a summary of growth and vision for my second innings as editor-in-chief.

As my second 5-year term as its editor-in-chief begins, it is important to review what BJPsych Open has accomplished, its areas of growth and what should be our future vision for the Journal. The keyword throughout this editorial is growth, with emphasis on growth in quality, for meaningful growth can only exist with increased quality. The original remit remains the correct long-term direction for the Journal, with the important modifier 'relevance' added to ensure quality - a general psychiatric journal with high-quality, methodologically rigorous and relevant publications, with relevance to the advancement of clinical care, patient outcomes, the scientific literature, research and policy. During this second term, I desire to expand the editorial board to fill expertise and diversity gaps; increase editorials and commentaries highlighting specific articles and timely events with psychiatric themes; focus on thematic series driven by the editorial board; and address under-represented topics.

Mechanisms of kidney injury in COVID-19 and diagnostic methods

The COVID-19 pandemic is a global healthcare crisis. The frequency of acute kidney injury (AKI) in patients with COVID-19 and the features of its diagnostics indicate the relevance of the topic. Objective of the review. To analyze mechanisms of AKI development in patients with COVID-19 and provide support for methodological approaches to ensure its timely diagnosis. Material and methods. The methodological approaches used in the review are based on a sufficient number of literature sources (more than 150 sources), of which 34 articles are included in the review: 15 original studies, 12 reviews, 2 meta-analyses, 5 re-ports, and letters to the editor. Results. The mechanisms of AKI development and progression, including the direct cytotoxic effect of the SARS-CoV-2 virus, dis-ruption of metabolic pathways of renal blood flow regulation, and the complement system, are considered. We also analyzed AKI risk factors in patients with acute respiratory distress: diabetes mellitus, chronic kidney injury, arterial hypertension with im-paired NOx production, and eNOS expression as significant factors of vasodilation in renal microcirculatory vessels. The analy-sis showed the most perspective directions in the diagnostics of AKI functional stages. These include molecular test methods (pro-teome and metabolome) in blood and urine;they helped define damage markers to proximal tubules and the glomerular system, thus improving the diagnostics accuracy and validity, therapy efficiency, and end points of disease prognosis. Conclusion. The Coronado study aims to assess the phenotypic features of patients with diabetes mellitus and COVID-19. More specific markers of the acute kidney injury functional stage were determined;these markers will improve the diagnostics accuracy and validity, therapy efficiency, and end points of disease prognosis.

Phytochemicals Against SARS-COV-2 Infection

Natural Product Communications Special Collection "Phytochemicals against SARS-COV-2 Infection" accepted 13 manuscripts, represented by 2 reviews, 9 original articles, and 1 letter to the editor. These deal with the use of traditional medicines, the use of network pharmacology, and docking studies to identify active compounds with prominent binding to various receptors responsible for internalization and replication, such as ACE2, S-protein, Mpro, PLpro, RdRp, and NSP15 endoribonuclease, as well as the possible use of phytochemicals against virus-associated inflammation. Copyright © The Author(s) 2023.