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In this study we focus on two subnetworks common in the circuitry of swim central pattern generators (CPGs) in the sea slugs, Melibe leonina and Dendronotus iris and show that they are independently capable of stably producing emergent network bursting. This observation raises the question of whether the coordination of redundant bursting mechanisms plays a role in the generation of rhythm and its regulation in the given swim CPGs. To address this question, we investigate two pairwise rhythm-generating networks and examine the properties of their fundamental components: cellular and synaptic, which are crucial for proper network assembly and its stable function. We perform a slow-fast decomposition analysis of cellular dynamics and highlight its significant bifurcations occurring in isolated and coupled neurons. A novel model for slow synapses with high filtering efficiency and temporal delay is also introduced and examined. Our findings demonstrate the existence of two modes of oscillation in bicellular rhythm-generating networks with network hysteresis: i) a half-center oscillator and ii) an excitatory-inhibitory pair. These 2-cell networks offer potential as common building blocks combined in modular organization of larger neural circuits preserving robust network hysteresis.

Cross-sectional studies have linked differences in white matter tissue properties to reading skills. However, past studies have reported a range of, sometimes conflicting, results. Some studies suggest that white matter properties act as individual-level traits predictive of reading skill, whereas others suggest that reading skill and white matter develop as a function of an individual’s educational experience. In the present study, we tested two hypotheses: a) that diffusion properties of the white matter reflect stable brain characteristics that relate to stable individual differences in reading ability or b) that white matter is a dynamic system, linked with learning over time. To answer these questions, we examined the relationship between white matter and reading in a five-year longitudinal dataset and a series of large-scale, single-observation, cross-sectional datasets (N = 14,249 total participants). We find that gains in reading skill correspond to longitudinal changes in the white matter. However, in the cross-sectional datasets, we find no evidence for the hypothesis that individual differences in white matter predict reading skill. These findings highlight the link between dynamic processes in the white matter and learning.

More than tools for managing physical and digital objects, museum collection management systems (CMS) serve as platforms for structuring, integrating, and making accessible the rich data embodied by natural history collections. Here we describe Arctos, a scalable community solution for managing and publishing global biological, geological, and cultural collections data for research and education. Specific goals are to: (1) Describe the core features and implementation of Arctos for a broad audience with respect to the biodiversity informatics principles that enable high quality research; (2) Highlight the unique aspects of Arctos; (3) Illustrate Arctos as a model for supporting and enhancing the Digital Extended Specimen concept; and (4) Emphasize the role of the Arctos community for improving data discovery and enabling cross-disciplinary, integrative studies within a sustainable governance model. In addition to detailing Arctos as both a community of museum professionals and a collection database platform, we discuss how Arctos achieves its richly annotated data by creating a web of knowledge with deep connections between catalog records and derived or associated data. We also highlight the value of Arctos as an educational resource. Finally, we present the financial model of fiscal sponsorship by a nonprofit organization, implemented in 2022, to ensure the long-term success and sustainability of Arctos.

Background: Use of ultrasound (US) to facilitate vascular access has increased compared to landmark-based procedures despite ergonomic challenges and need for extrapolation of 2-dimensional images to understand needle position. The MantUS™ system (Sentiar, Inc.,) uses a mixed reality (MxR) interface to display US images and integrate real-time needle tracking. Objective: The purpose of this prospective preclinical study was to evaluate the feasibility and usability of MantUS in a simulated environment. Methods: Participants were recruited from pediatric cardiology and critical care. Access was obtained in 2 vascular access training models: a femoral access model and a head and neck model for a total of 4 vascular access sites under 2 conditions—conventional US and MantUS. Participants were randomized for order of completion. Videos were obtained, and quality of access including time required, repositions, number of attempts, and angle of approach were quantified. Results: Use of MantUS resulted in an overall reduction in number of needle repositions (P = .03) and improvement in quality of access as measured by distance (P

ABSTRACT Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Introduction Type 1 diabetes (T1D) is a chronic and incurable autoimmune disease, diagnosed in early childhood and managed initially in paediatric healthcare services. In many countries, including Australia, national audit data suggest that management and care of T1D, and consequently glycaemic control, are consistently poor. This can lead to adverse outcomes such as cardiovascular disease and nephropathy. T1D treatment is complex, multidisciplinary, multiagency and life-long and should involve patient-centred, developmentally appropriate care. Although an emerging body of literature describes T1D models of care, their components, implementation determinants and associated outcomes are poorly understood.Objectives To provide a study protocol to describe methods to map existing models of care for children and young adults living with T1D. It will identify the gaps and needs in care delivery as viewed by healthcare providers and by children, young people and their families accessing care in metropolitan and rural or remote regions throughout Australia.Methods and analysis A mixed-method study that includes provider and consumer-specific surveys and interviews about current T1D care provisions. Data will be analysed thematically (qualitative) and statistically (quantitative) and synthesised to describe the key characteristics of effective and sustainable models of care for T1D and to identify gaps.Ethics and dissemination Ethics approval was granted by the Macquarie University Human Research Ethics Committee in July 2022 (#520221154439676). Results will be disseminated via publication in peer-reviewed journals and at relevant conferences.

New vaccine introductions (NVIs) raise issues of value for money (VfM) for self-financing middle-income countries like Egypt. We evaluate a pediatric pneumococcal conjugate vaccine (PCV) NVI in Egypt from health payer and societal perspectives, using cost-utility and cost-benefit analysis (CUA, CBA). We evaluate vaccinating 100 successive birth cohorts with the 13-valent PCV (“PCV13”) and the 10-valent PCV (“PCV10”) relative to no vaccination and each other. We quantify health effects with a disease incidence projection model and a multiple-cohort static disease model. Our CBA uses a health-augmented lifecycle model to generate willingness-to-pay for health gains from which we calculate rates of return (RoR). We obtain parameters from the published literature. We perform deterministic and probabilistic sensitivity analysis. Our base-case CUA finds incremental cost-effectiveness ratios (ICERs) for PCV13 and PCV10 relative to no program of $926 (95% confidence interval $512–$1,735) and $1,984 ($1,186-$3,805) per quality-adjusted life year (QALY), respectively; and for PCV13 relative to PCV10 of $174 ($88-$331) per QALY. Our base-case CBA finds RoRs to PCV13 and PCV10 relative to no program of 488% (188–993%) and 164% (33–336%), respectively, and to PCV13 relative to PCV10 of 3109% (1410–6602%). Both CUA and CBA find PCV13 to be good VfM relative to PCV10.

The use of innovative imaging practices in the field of interventional cardiology and electrophysiology has led to significant progress in both diagnostic and therapeutic capabilities. 3D reconstructions of 2D images allows a proceduralist to develop a superior understanding of patient anatomy. Medical extended reality (MXR) technologies employ 3D interactive images for the user to improve depth perception and spatial awareness. Although MXR procedural navigation is a relatively new concept, the potential for use within interventional cardiology and EP is significant with the eventual goal of improving patient outcomes and reducing patient harm. This review article will discuss the current landscape of MXR use in the catheterization lab including pre-procedural planning, intraprocedural planning and intraprocedural guidance in diagnostic cardiac catheterization, valvar and coronary interventions, electrophysiology studies, and device implants.

Abstract Background Value assessment of vaccination programs against serogroup B invasive meningococcal disease (IMD) is on the agenda of public health authorities. Current evidence on the burden due to IMD is unfit for pinning down the nature and magnitude of the full social and economic costs of IMD for two reasons. First, the concepts and components that need to be studied are not agreed, and second, measures of the concepts that have been studied are weak and inconsistent. Thus, the economic evaluation of the available serogroup B meningococcal (MenB) vaccines is difficult. The aims of this DELPHI study are to: (1) agree on the concepts and components determining the burden of MenB diseases that need to be studied; and (2) seek consensus on appropriate methods and study designs to measure quality of life (QoL) associated with MenB induced long-term sequelae in future studies. Methods We designed a DELPHI questionnaire based on the findings of a recent systematic review on the QoL associated with IMD-induced long-term sequelae, and iteratively interviewed a panel of international experts, including physicians, health economists, and patient representatives. Experts were provided with a controlled feedback based on the results of the previous round. Results Experts reached consensus on all questions after two DELPHI rounds. Major gaps in the literature relate (i) to the classification of sequelae, which allows differentiation of severity levels, (ii) to the choice of QoL measures, and (iii) to appropriate data sources to examine long-term changes and deficits in patients’ QoL. Conclusions Better conceptualisation of the structure of IMD-specific sequelae and of how their diverse forms of severity might impact the QoL of survivors of IMD as well as their family network and care-providers is needed to generate relevant, reliable and generalisable data on QoL in the future. The results of this DELPHI panel provide useful guidance on how to choose the study design, target population and appropriate QoL measures for future research and hence, help promote the appropriateness and consistency in study methodology and sample characteristics.

Introduction The current diagnostic pathways for cognitive impairment rarely identify babies at risk before 2 years of age. Very early detection and timely targeted intervention has potential to improve outcomes for these children and support them to reach their full life potential. Early Moves aims to identify early biomarkers, including general movements (GMs), for babies at risk of cognitive impairment, allowing early intervention within critical developmental windows to enable these children to have the best possible start to life.Method and analysis Early Moves is a double-masked prospective cohort study that will recruit 3000 term and preterm babies from a secondary care setting. Early Moves will determine the diagnostic value of abnormal GMs (at writhing and fidgety age) for mild, moderate and severe cognitive delay at 2 years measured by the Bayley-4. Parents will use the Baby Moves smartphone application to video their babies’ GMs. Trained GMs assessors will be masked to any risk factors and assessors of the primary outcome will be masked to the GMs result. Automated scoring of GMs will be developed through applying machine-based learning to the data and the predictive value for an abnormal GM will be investigated. Screening algorithms for identification of children at risk of cognitive impairment, using the GM assessment (GMA), and routinely collected social and environmental profile data will be developed to allow more accurate prediction of cognitive outcome at 2 years. A cost evaluation for GMA implementation in preparation for national implementation will be undertaken including exploring the relationship between cognitive status and healthcare utilisation, medical costs, health-related quality of life and caregiver burden.Ethics and dissemination Ethics approval has been granted by the Medical Research Ethics Committee of Joondalup Health Services and the Health Service Human Research Ethics Committee (1902) of Curtin University (HRE2019-0739).Trial registration number ACTRN12619001422112.

The high price of new generations of vaccines relative to their predecessors has become an important consideration in debates over whether the benefits of the new vaccines justify their costs. An increasingly central line of inquiry in the literature on valuing vaccination surrounds accounting for the full social and economic benefits of vaccination. This paper applies this emerging perspective to the particular case of vaccination against serogroup B meningococcal disease (MenB). We explore key issues involved in health technology assessments of MenB vaccination, which have led to pronounced heterogeneity in evaluation methods and recommendation outcomes across countries such as France, Germany, the US, and the UK. Accounting for typically neglected sources of socioeconomic benefit could potentially impact recommendation and reimbursement decisions. We propose a taxonomy of such benefits built around four dimensions: (i) internalized health benefits, (ii) internalized non-health benefits, (iii) externalized health benefits, and (iv) externalized non-health benefits. This approach offers a systematic, comprehensive evaluation framework that can be used in future assessment of MenB vaccines as well as other health technologies.

Georeferencing is the process of aligning a text description of a geographic location with a spatial location based on a geographic coordinate system. Training aids are commonly created around the georeferencing process to disseminate community standards and ideas, guide accurate georeferencing, inform users about new tools, and help users evaluate existing geospatial data. The Georeferencing for Research Use (GRU) workshop was implemented as a training aid that focused on the creation and research use of geospatial coordinates, and included both data researchers and data providers, to facilitate communication between the groups. The workshop included 23 participants with a wide background of expertise ranging from students (undergraduate and graduate), professors, researchers and educators, scientific data managers, natural history collections personnel, and spatial analyst specialists. The conversations and survey results from this workshop demonstrate that it is important to provide opportunities for biocollections data providers to interact directly with the researchers using the data they produce and vice versa.

Abstract Background A variety of neurological disorders including neurodegenerative diseases and infection by neurotropic viruses can cause structural and functional changes in the central nervous system (CNS), resulting in long-term neurological sequelae. An improved understanding of the pathogenesis of these disorders is important for developing efficacious interventions. Human induced pluripotent stem cells (hiPSCs) offer an extraordinary window for modeling pathogen-CNS interactions, and other cellular interactions, in three-dimensional (3D) neuronal cultures that can recapitulate several aspects of in vivo brain tissue. Methods Herein, we describe a prototype of scaffold-free hiPSC-based adherent 3D (A-3D) human neuronal cultures in 96-well plates. To test their suitability for drug screening, A-3D neuronal cultures were infected with herpes simplex virus type 1 (HSV-1) with or without acyclovir. Results The half maximal inhibitory concentration (IC50) of acyclovir was 3.14 μM and 3.12 μM determined using flow cytometry and the CX7 High Content Screening platform, respectively. Conclusions Our A-3D neuronal cultures provide an unprecedented opportunity for high-content drug screening programs to treat human CNS infections.

Objective: To ensure that resources designed to teach skills and best practices for scientific research data sharing and management are useful, the maintainers of those materials need to evaluate and update them to ensure their accuracy, currency, and quality. This paper advances the use and process of outside peer review for community resources in addressing ongoing accuracy, quality, and currency issues. It further describes the next step of moving the updated materials to an online collaborative community platform for future iterative review in order to build upon mechanisms for open science, ongoing iteration, participation, and transparent community engagement. Setting: Research data management resources were developed in support of the DataONE (Data Observation Network for Earth) project, which has deployed a sustainable, long-term network to ensure the preservation and access to multi-scale, multi-discipline, and multi-national environmental and biological science data (Michener et al. 2012). Created by members of the Community Engagement and Education (CEE) Working Group in 2011-2012, the freely available Educational Modules included three complementary components (slides, handouts, and exercises) that were designed to be adaptable for use in classrooms as well as for research data management training. Methods: Because the modules were initially created and launched in 2011-2012, the current members of the (renamed) Community Engagement and Outreach (CEO) Working Group were concerned that the materials could be and / or quickly become outdated and should be reviewed for accuracy, currency, and quality. In November 2015, the Working Group developed an evaluation rubric for use by outside reviewers. Review criteria were developed based on surveys and usage scenarios from previous DataONE projects. Peer reviewers were selected from the DataONE community network for their expertise in the areas covered by one of the 11 educational modules. Reviewers were contacted in March 2016, and were asked to volunteer to complete their evaluations online within one month of the request, by using a customized Google form. Results: For the 11 modules, 22 completed reviews were received by April 2016 from outside experts. Comments on all three components of each module (slides, handouts, and exercises) were compiled and evaluated by the postdoctoral fellow attached to the CEO Working Group. These reviews contributed to the full evaluation and revision by members of the Working Group of all educational modules in September 2016. This review process, as well as the potential lack of funding for ongoing maintenance by Working Group members or paid staff, provoked the group to transform the modules to a more stable, non-proprietary format, and move them to an online open repository hosting platform, GitHub. These decisions were made to foster sustainability, community engagement, version control, and transparency. Conclusion: Outside peer review of the modules by experts in the field was beneficial for highlighting areas of weakness or overlap in the education modules. The modules were initially created in 2011-2012 by an earlier iteration of the Working Group, and updates were needed due to the constant evolving practices in the field. Because the review process was lengthy (approximately one year) comparative to the rate of innovations in data management practices, the Working Group discussed other options that would allow community members to make updates available more quickly. The intent of migrating the modules to an online collaborative platform (GitHub) is to allow for iterative updates and ongoing outside review, and to provide further transparency about accuracy, currency, and quality in the spirit of open science and collaboration. Documentation about this project may be useful for others trying to develop and maintain educational resources for engagement and outreach, particularly in communities and spaces where information changes quickly, and open platforms are already in common use.

Herpes simplex virus (HSV) establishes a latent infection within sensory neurons of humans. Latency is characterized by the transcriptional repression of lytic genes by the condensation of lytic gene regions into heterochromatin. Recent data suggest that facultative heterochromatin predominates, and that cellular Polycomb proteins are involved in the establishment and maintenance of transcriptional repression during latency. This review summarizes these data and discusses the implication of viral and cellular factors in regulating heterochromatin composition.

Biological field notebooks are records of lives spent outside in nature. Part diary, part scientific record, field notebooks often contain details required to understand the location and environmental conditions existent during collecting events. Despite their clear value for (and recent use in) global change studies, the text-mining outputs from field notebooks have been idiosyncratic to specific research projects, and impossible to discover or re-use. Best practices and workflows for digitization, transcription, extraction, and integration with other sources are nascent or non-existent. In this paper, we demonstrate a model workflow to generate structured outputs while also maintaining linkages to the original texts. The first step in this workflow was placing already digitized and transcribed field notebooks from the University of Colorado Museum of Natural History founder, Junius Henderson, on Wikisource, an open manuscript-editing platform. Next, we created Wikisource-specific templates to document places, dates, and taxa to facilitate annotation and wiki-linking. We then requested help from the public, through social media tools, to take advantage of volunteer efforts and energy. After three notebooks were fully annotated, content was converted into XML and annotations were extracted and placed into Darwin Core compliant record sets. Finally, these record sets were vetted, specifically to provide valid taxon names, via a process we call “taxonomic referencing.” The result is identification and mobilization of 1076 observations from three of Henderson’s thirteen notebooks and a publishable Darwin Core record set for use in other analyses. Although challenges remain, this work demonstrates a feasible approach to unlock observations from field notebooks that enhances their discovery and interoperability without losing the narrative context from which those observations are drawn.

The planet is experiencing an ongoing global biodiversity crisis. Measuring the magnitude and rate of change more effectively requires access to organized, easily discoverable, and digitally-formatted biodiversity data, both legacy and new, from across the globe. Assembling this coherent digital representation of biodiversity requires the integration of data that have historically been analog, dispersed, and heterogeneous. The Integrated Publishing Toolkit (IPT) is a software package developed to support biodiversity dataset publication in a common format. The IPT's two primary functions are to 1) encode existing species occurrence datasets and checklists, such as records from natural history collections or observations, in the Darwin Core standard to enhance interoperability of data, and 2) publish and archive data and metadata for broad use in a Darwin Core Archive, a set of files following a standard format. Here we discuss the key need for the IPT, how it has developed in response to community input, and how it continues to evolve to streamline and enhance the interoperability, discoverability, and mobilization of new data types beyond basic Darwin Core records. We close with a discussion how IPT has impacted the biodiversity research community, how it enhances data publishing in more traditional journal venues, along with new features implemented in the latest version of the IPT, and future plans for more enhancements.

ChIP-seq experiments identify genome-wide profiles of DNA-binding molecules including transcription factors, enzymes and epigenetic marks. Biological replicates are critical for reliable site discovery and are required for the deposition of data in the ENCODE and modENCODE projects. While early reports suggested two replicates were sufficient, the widespread application of the technique has led to emerging consensus that the technique is noisy and that increasing replication may be worthwhile. Additional biological replicates also allow for quantitative assessment of differences between conditions. To date it has remained controversial about how to confirm peak identification and to determine signal strength across biological replicates, particularly when the number of replicates is greater than two. Using objective metrics, we evaluate the consistency of biological replicates in ChIP-seq experiments with more than two replicates. We compare several approaches for binding site determination, including two popular but disparate peak callers, CisGenome and MACS2. Here we propose read coverage as a quantitative measurement of signal strength for estimating sample concordance. Determining binding based on genomic features, such as promoters, is also examined. We find that increasing the number of biological replicates increases the reliability of peak identification. Critically, binding sites with strong biological evidence may be missed if researchers rely on only two biological replicates. When more than two replicates are performed, a simple majority rule (>50% of samples identify a peak) identifies peaks more reliably in all biological replicates than the absolute concordance of peak identification between any two replicates, further demonstrating the utility of increasing replicate numbers in ChIP-seq experiments.