The Path Forward: A Post-Omicron Strategy for the Global COVID-19 Response

At this pivotal moment, the world's response to the pandemic must shift from emergency crisis management to a sustainable control strategy. This strategy should help to build resilient health systems with capabilities to address potential future COVID-19 outbreaks and other public health threats. Driving the urgent need for an updated strategy are important recent developments related to the SARS-CoV-2 virus, the impact of current vaccines, and the world's response to the pandemic

The Redox-Sensitive Transcriptional Activator OxyR Regulates the Peroxide Response Regulon in the Obligate Anaerobe Bacteroides fragilis

The peroxide response-inducible genes ahpCF, dps, and katB in the obligate anaerobe Bacteroides fragilis are controlled by the redox-sensitive transcriptional activator OxyR. This is the first functional oxidative stress regulator identified and characterized in anaerobic bacteria. oxyR and dps were found to be divergently transcribed, with an overlap in their respective promoter regulatory regions. B. fragilis OxyR and Dps proteins showed high identity to homologues from a closely related anaerobe, Porphyromonas gingivalis. Northern blot analysis revealed that oxyR was expressed as a monocistronic 1-kb mRNA and that dps mRNA was approximately 500 bases in length. dps mRNA was induced over 500-fold by oxidative stress in the parent strain and was constitutively induced in the peroxide-resistant mutant IB263. The constitutive peroxide response in strain IB263 was shown to have resulted from a missense mutation at codon 202 (GAT to GGT) of the oxyR gene [oxyR(Con)] with a predicted D202G substitution in the OxyR protein. Transcriptional fusion analysis revealed that deletion of oxyR abolished the induction of ahpC and katB following treatment with hydrogen peroxide or oxygen exposure. However, dps expression was induced approximately fourfold by oxygen exposure in DoxyR strains but not by hydrogen peroxide. This indicates that dps expression is also under the control of an oxygen-dependent OxyR-independent mechanism. Complementation of DoxyR mutant strains with wildtype oxyR and oxyR(Con) restored the inducible peroxide response and the constitutive response of the ahpCF, katB, and dps genes, respectively. However, overexpression of OxyR abolished the catalase activity but not katB expression, suggesting that higher levels of intracellular OxyR may be involved in other physiological processes. Analysis of oxyR expression in the parents and in DoxyR and overexpressing oxyR strains by Northern blotting and oxyR*::xylB fusions revealed that B. fragilis OxyR does not control its own expression. Originally published Journal of Bacteriology, Vol. 182, No. 18, Sep. 200

Team 3: Exploring the relationship of systems research to systems literacy

In this paper, the Systems Research Team (SRT) details the activities and outcomes of the 2016 IFSR Conversation in Linz, Austria. The 2016 SRT includes: Mary Edson (team leader), Pam Buckle Henning, Tim Ferris, Andreas Hieronymi, Ray Ison, Gary Metcalf, George Mobus, Nam Nguyen, David Rousseau, and Shankar Sankaran, with guest team member, Peter Tuddenham, anchoring the endeavor in Systems Literacy. While the 2014 SRT’s focus was answering the question, “What distinguishes Systems Research from other types of research?” an internal focus intended to provide grounding for researchers new to the Systems Sciences, the 2016 SRT’s focus is on reaching out to a broader community in order to provide a foundation for Systems Literacy. The team’s Conversation revolved around the question, “How can Systems Research be in service to Systems Literacy?” The team’s discussions were directed into two essential aspects, separate and integrated, of this question. First, Systems Research serves Systems Literacy by providing a credible foundation for the principles and practices of Systems Science and Systems Thinking in both systematic and systemic modes. Second, Systems Research provides a neutral frame for development of ethical applications of those principles and practices. The SRT recognizes the exigency in providing foundational principles that can be effectively adopted and disseminated through Systems Literacy. The team’s narrative begins with an understanding the urgency for application of Systems Sciences and Systems Thinking to critical issues. Systems research, as with other types of research, is typically a slow generation of results; however, the body of knowledge gained through this process can be confidently used to address complexity in timely ways. The criticality of the need for salient approaches to complexity is shown in a graphic representation of some possible trajectories of applying or not applying these Systems principles in practice. The choice of how we respond to these issues relates to a process model that can be applied. Through understanding the relationship of the process model to the trajectory, the team directed its focus to developing a MindMap (Eppler, 2006) of eight essential aspects or features of how Systems Research can support Systems Literacy. These include: Systems Science knowledge base, roles and personas, maturity models, role profile, ontology/vocabulary, perspective/framing choice, frameworks, and political ecology. Each of these eight has its own process of unpacking, which was demonstrated to the Conversation participants by delving more deeply into the aspect of knowledge base. The eight relate to unpacking the Systems landscape in a coherent but loosely coupled investment portfolio (economic, social, and relational) for building systemic sensibility in such a way as to be dis/aggregated for different audiences. The week’s work culminated in a plan for “Looking Ahead,” which outlines the intentions of the SRT to continue its activities in support of Systems Literacy in the upcoming months. An example of this continued work is a workshop, “Toward Systems Literacy, the Role of Systems Research,” that was conducted at the 60th Meeting of the International Society for the Systems Sciences in Boulder, July 25, 2016

The electrophysiological response to polarization-modulated patterned visual stimuli

Recent reports indicate that the subjective ability of humans to discriminate between polarization E-vector orientations approaches that of many invertebrates. Here, we show that polarization-modulated patterned stimuli generate an objectively recordable electrophysiological response in humans with normal vision. We investigated visual evoked potential (VEP) and electroretinographic (ERG) responses to checkerboard patterns defined solely by their polarization E-vector orientation alternating between ± 45°. Correcting for multiple comparisons, paired-samples t-tests were conducted to assess the significance of post-stimulus deflections from baseline measures of noise. Using standard check pattern sizes for clinical electrophysiology, and a pattern-reversal protocol, participants showed a VEP response to polarization-modulated patterns (PolVEP) with a prominent and consistent positive component near 150 ms (p 550 nm. Further, pseudo-depolarization negated the responses, while control studies provided confirmatory evidence that the PolVEP response was not the product of luminance artefacts. Polarization-modulated patterns did not elicit a recordable ERG response. The possible origins of the PolVEP signals, and the absence of recordable ERG signals, are discussed. We conclude that evoked cortical responses to polarization-modulated patterns provide an objective measure of foveal function, suitable for both humans and non-human primates with equivalent macular anatom

Dislocation of the testis as a delayed presentation of scrotal trauma

Traumatic dislocation of the testis is a rare event in which the full extent of the dislocation is present immediately following the initial trauma. We present a case in which the testicular dislocation progressed over a period of four days following the initial scrotal trauma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31939/1/0000892.pd

Biocarbon ureterostomy device for urinary diversion Multicenter clinical trial

The bioCarbon ureterostomy device is a stomal prosthesis for upper tract urinary diversion that has had preliminary successes in animal and human trials in Europe and Peru. Implantation of a pure carbon stomal prosthesis offers the potential advantages of high biocompatibility, lack of encrustation, and elimination of stomal stenosis which is frequently associated with cutaneous ureterostomy. Nine bioCarbon ureterostomy devices were implanted from August, 1984 through July, 1985. Although successful implantation was achieved in 2 patients, the complication rate was high. The bioCarbon ureterostomy device has potential as an alternative form of urinary diversion. However, significant problems need to be remedied before it can be recommended for routine clinical application.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28101/1/0000548.pd

Androgen Receptor Inhibition Suppresses Anti-Tumor Neutrophil Response Against Bone Metastatic Prostate Cancer via Regulation of TβRI Expression

Bone metastatic disease of prostate cancer (PCa) is incurable and progression in bone is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that bone neutrophils initially inhibit bone metastatic PCa growth yet metastatic PCa becomes resistant to neutrophil response. Further, neutrophils isolated from tumor-bone lost their ability to suppress tumor growth through unknown mechanisms. With this study, our goal was to define the impact of metastatic PCa on neutrophil function throughout tumor progression and to determine the potential of neutrophils as predictive biomarkers of metastatic disease. Using patient peripheral blood polymorphonuclear neutrophils (PMNs), we identified that PCa progression dictates PMN cell surface markers and gene expression, but not cytotoxicity against PCa. Importantly, we also identified a novel phenomenon in which second generation androgen deprivation therapy (ADT) suppresses PMN cytotoxicity via increased transforming growth factor beta receptor I (TβRI). High dose testosterone and genetic or pharmacologic TβRI inhibition rescued androgen receptor-mediated neutrophil suppression and restored neutrophil anti-tumor immune response. These studies highlight the ability to leverage standard-care ADT to generate neutrophil anti-tumor responses against bone metastatic PCa

Synchronous shedding of multiple bat paramyxoviruses coincides with peak periods of Hendra virus spillover

Within host-parasite communities, viral co-circulation and co-infections of hosts are the norm, yet studies of significant emerging zoonoses tend to focus on a single parasite species within the host. Using a multiplexed paramyxovirus bead-based PCR on urine samples from Australian flying foxes, we show that multi-viral shedding from flying fox populations is common. We detected up to nine bat paramyxoviruses shed synchronously. Multi-viral shedding infrequently coalesced into an extreme, brief and spatially restricted shedding pulse, coinciding with peak spillover of Hendra virus, an emerging fatal zoonotic pathogen of high interest. Such extreme pulses of multi-viral shedding could easily be missed during routine surveillance yet have potentially serious consequences for spillover of novel pathogens to humans and domestic animal hosts. We also detected co-occurrence patterns suggestive of the presence of interactions among viruses, such as facilitation and cross-immunity. We propose that multiple viruses may be interacting, influencing the shedding and spillover of zoonotic pathogens. Understanding these interactions in the context of broader scale drivers, such as habitat loss, may help predict shedding pulses of Hendra virus and other fatal zoonoses

Heliophysics and Amateur Radio:Citizen Science Collaborations for Atmospheric, Ionospheric, and Space Physics Research and Operations

The amateur radio community is a global, highly engaged, and technical community with an intense interest in space weather, its underlying physics, and how it impacts radio communications. The large-scale observational capabilities of distributed instrumentation fielded by amateur radio operators and radio science enthusiasts offers a tremendous opportunity to advance the fields of heliophysics, radio science, and space weather. Well-established amateur radio networks like the RBN, WSPRNet, and PSKReporter already provide rich, ever-growing, long-term data of bottomside ionospheric observations. Up-and-coming purpose-built citizen science networks, and their associated novel instruments, offer opportunities for citizen scientists, professional researchers, and industry to field networks for specific science questions and operational needs. Here, we discuss the scientific and technical capabilities of the global amateur radio community, review methods of collaboration between the amateur radio and professional scientific community, and review recent peer-reviewed studies that have made use of amateur radio data and methods. Finally, we present recommendations submitted to the U.S. National Academy of Science Decadal Survey for Solar and Space Physics (Heliophysics) 2024–2033 for using amateur radio to further advance heliophysics and for fostering deeper collaborations between the professional science and amateur radio communities. Technical recommendations include increasing support for distributed instrumentation fielded by amateur radio operators and citizen scientists, developing novel transmissions of RF signals that can be used in citizen science experiments, developing new amateur radio modes that simultaneously allow for communications and ionospheric sounding, and formally incorporating the amateur radio community and its observational assets into the Space Weather R2O2R framework. Collaborative recommendations include allocating resources for amateur radio citizen science research projects and activities, developing amateur radio research and educational activities in collaboration with leading organizations within the amateur radio community, facilitating communication and collegiality between professional researchers and amateurs, ensuring that proposed projects are of a mutual benefit to both the professional research and amateur radio communities, and working towards diverse, equitable, and inclusive communities