Predicting the spatio-temporal infection risk in indoor spaces using an efficient airborne transmission model

We develop a spatially dependent generalization to the Wells–Riley model, which determines the infection risk due to airborne transmission of viruses. We assume that the infectious aerosol concentration is governed by an advection–diffusion–reaction equation with the aerosols advected by airflow, diffused due to turbulence, emitted by infected people, and removed due to ventilation, inactivation of the virus and gravitational settling. We consider one asymptomatic or presymptomatic infectious person breathing or talking, with or without a mask, and model a quasi-three-dimensional set-up that incorporates a recirculating air-conditioning flow. We derive a semi-analytic solution that enables fast simulations and compare our predictions to three real-life case studies—a courtroom, a restaurant, and a hospital ward—demonstrating good agreement. We then generate predictions for the concentration and the infection risk in a classroom, for four different ventilation settings. We quantify the significant reduction in the concentration and the infection risk as ventilation improves, and derive appropriate power laws. The model can be easily updated for different parameter values and can be used to make predictions on the expected time taken to become infected, for any location, emission rate, and ventilation level. The results have direct applicability in mitigating the spread of the COVID-19 pandemic

Pathways to care for critically ill or injured children: A cohort study from first presentation to healthcare services through to admission to intensive care or death

Purpose Critically ill or injured children require prompt identification, rapid referral and quality emergency management. We undertook a study to evaluate the care pathway of critically ill or injured children to identify preventable failures in the care provided. METHODS: A year-long cohort study of critically ill and injured children was performed in Cape Town, South Africa, from first presentation to healthcare services until paediatric intensive care unit (PICU) admission or emergency department death, using expert panel review of medical records and caregiver interview. Main outcomes were expert assessment of overall quality of care; avoidability of severity of illness and PICU admission or death and the identification of modifiable factors. RESULTS: The study enrolled 282 children, 252 emergency PICU admissions, and 30 deaths. Global quality of care was graded good in 10% of cases, with half having at least one major impact modifiable factor. Key modifiable factors related to access to care and identification of the critically ill, assessment of severity, inadequate resuscitation, and delays in decision making and referral. Children were transferred with median time from first presentation to PICU admission of 12.3 hours. There was potentially avoidable severity of illness in 185 (74%) of children, and death prior to PICU admission was avoidable in 17/30 (56.7%) of children. CONCLUSIONS: The study presents a novel methodology, examining quality of care across an entire system, and highlighting the complexity of the pathway and the modifiable events amenable to interventions, that could reduce mortality and morbidity, and optimize utilization of scarce critical care resources; as well as demonstrating the importance of continuity and quality of care

Drug delivery formulation impacts cyclosporine efficacy in a humanised mouse model of acute graft versus host disease

Acute graft versus host disease (aGvHD) is an allogeneic T cell mediated disease which manifests as a severe inflammatory disease affecting multiple organs including the liver, skin, lungs and gastrointestinal tract. Existing prophylactic and therapeutic approaches in aGvHD include the use of cyclosporine A (CyA), however the currently approved CyA formulations which were designed to optimise systemic CyA bioavailability can have a number of side effects including nephrotoxicity as well as the potential to attenuate the beneficial Graft-versus-Leukemia (GvL) effect. An added complication with CyA is that it has a narrow therapeutic window, and following oral administration is absorbed only from the small intestine, with variable cytochrome P450 metabolism contributing to intra- and inter-patient variability. This study sought to investigate the efficacy of a novel CyA oral formulation enabled by the integrated SmPill® oral drug delivery platform in a humanised mouse model of aGvHD. The study compared the approved optimised CyA (Neoral®) with SmPill®-enabled CyA and a systemic intravenous CyA formulation. Our findings clearly demonstrate superior efficacy of the novel SmPill® CyA in prolonging survival in a clinically relevant humanised aGvHD model. SmPill® CyA significantly reduced pathological score in the small intestine, colon, liver and lung of aGvHD mice. In addition, SmPill® CyA significantly reduced the levels of pro-inflammatory cytokines in all the GvHD target tissues examined. Notably, SmPill® CyA was significantly more potent in reducing GvHD associated pathology and inflammatory cytokine production compared to the optimised approved oral CyA formulation, Neoral®

An allometric scaling relationship in the brain of preterm infants

Allometry has been used to demonstrate a power–law scaling relationship in the brain of premature born infants. Forty-nine preterm infants underwent neonatal MRI scans and neurodevelopmental testing at age 2. Measures of cortical surface area and total cerebral volume demonstrated a power–law scaling relationship (α = 1.27). No associations were identified between these measures and investigated clinical variables. Term equivalent cortical surface area and total cerebral volume measures and scaling exponents were not related to outcome. These findings confirm a previously reported allometric scaling relationship in the preterm brain, and suggest that scaling is not a sensitive indicator of aberrant cortical maturation

Cyclosporine A and IFNγ licencing enhances human mesenchymal stromal cell potency in a humanised mouse model of acute graft versus host disease

Immunosuppressive ability in human MSC donors has been shown to be variable and may be a limiting factor in MSC therapeutic efficacy in vivo. The importance of cytokine activation of mesenchymal stromal cells (MSCs) to facilitate their immunosuppressive function is well established. This study sought to further understand the interactions between MSCs and the commonly used calcineurin inhibitor cyclosporine A (CsA). The existing literature regarding approaches that use MSCs and cyclosporine are conflicting regarding the effect of CsA on MSC potency and function. Here, we clearly demonstrate that when added at the same time as MSCs, CsA negatively affects MSC suppression of T cell proliferation. However, licencing MSCs with IFNγ before addition of CsA protects MSCs from this negative effect. Notably, adding CsA to MSCs after IFNγ pre-stimulation enhances MSC production of IDO. Mechanistically, we identified that CsA reduces SOCS1 expression to facilitate enhanced IDO production in IFNγ pre-stimulated MSCs. Importantly, CsA exposure to IFNγ pre-stimulated MSC before administration, significantly enhanced the potency of MSCs in a human relevant humanised mouse model of acute Graft versus Host Disease. In summary, this study identified a novel licencing strategy to enhance MSC potency in vitro and in vivo

IFN-γ and PPARδ Influence the Efficacy and Retention of Multipotent Adult Progenitor Cells in Graft vs Host Disease

Cell-based therapy for the treatment of inflammatory disorders has focused on the application of mesenchymal stromal cells (MSCs) and multipotent adult progenitor cells (MAPCs). Despite the recent positive findings in industry-sponsored clinical trials of MSCs and MAPCs for graft vs host disease (GvHD), cell therapy is efficacious in some but not all patients, highlighting the need to identify strategies to enhance cell-based therapeutic efficacy. Here, we demonstrate the capacity for interferon (IFN)-γ licensing to enhance human MAPC efficacy and retention following early administration in a humanized mouse model of acute GvHD (aGvHD). Activation of the nuclear receptor peroxisome proliferator-activated receptor delta (PPARδ) negatively influenced the retention and efficacy of human MAPCs as well as IFNγ-licensed MAPCs in the aGvHD model. PPARδ antagonism significantly enhanced the efficacy of human MAPCs when administered early in the humanized aGvHD model. COX-2 expression in human MAPC was significantly decreased in IFN-γ licensed MAPCs exposed to a PPARδ agonist. Importantly, MAPC exposure to the PPARδ antagonist in the presence of a COX-2 inhibitor indomethacin before administration significantly reduced the efficacy of PPARδ antagonized MAPCs in the aGvHD humanized mouse model. This is the first study to demonstrate the importance of PPARδ in human MAPC efficacy in vivo and highlights the importance of understanding the disease microenvironment in which cell-based therapies are to be administered. In particular, the presence of PPARδ ligands may negatively influence MAPC or MSC therapeutic efficacy

Political geographies of the object

This paper examines the role of objects in the constitution and exercise of state power, drawing on a close reading of the acclaimed HBO television series The Wire, an unconventional crime drama set and shot in Baltimore, Maryland. While political geography increasingly recognizes the prosaic and intimate practices of stateness, we argue that objects themselves are central to the production, organization, and performance of state power. Specifically, we analyze how three prominent objects on The Wire—wiretaps, cameras, and standardized tests—arrange and produce the conditions we understand as ‘stateness’. Drawing on object-oriented philosophy, we offer a methodology of power that suggests it is generalized force relations rather than specifically social relations that police a population—without, of course, ever being able to fully capture it. We conclude by suggesting The Wire itself is an object of force, and explore the implications of an object-oriented approach for understanding the nature of power, and for political geography more broadly

Rethinking irrigation modernisation: Realising multiple objectives through the integration of fisheries

Irrigation has been, and will remain, instrumental in addressing water security (Sustainable Development Goal (SDG) 6), food insecurity (SDG 2) and poverty (SDG 1) goals. However, the global context in which irrigation takes place is changing rapidly. A call for healthier and more sustainable food systems is placing new demands on how irrigation is developed and managed. Growing pressures from competing water uses in the domestic and industrial sectors, as well increasing environmental awareness, mean irrigation is increasingly called on to perform better, delivering acceptable returns on investment and simultaneously improving food security, rural livelihoods and nutrition, as well as supporting environmental conservation. Better integration of fisheries (including aquaculture) in irrigation planning, investment and management can contribute to the modernisation of irrigation and the achievement of the multiple objectives that it is called on to deliver. A framework illustrating how fisheries can be better integrated with irrigation, and how the two can complement each other across a range of scales, from scheme to catchment and, ultimately, national level, is presented

MeerKAT uncovers the physics of an odd radio circle

Odd radio circles (ORCs) are recently-discovered faint diffuse circles of radio emission, of unknown cause, surrounding galaxies at moderate redshift (z ∼0.2-0.6). Here, we present detailed new MeerKAT radio images at 1284 MHz of the first ORC, originally discovered with the Australian Square Kilometre Array Pathfinder, with higher resolution (6 arcsec) and sensitivity (∼2.4 μJy/beam). In addition to the new images, which reveal a complex internal structure consisting of multiple arcs, we also present polarization and spectral index maps. Based on these new data, we consider potential mechanisms that may generate the ORCs

Genome assembly and gene expression in the American black bear provides new insights into the renal response to hibernation.

The prevalence of chronic kidney disease (CKD) is rising worldwide and 10-15% of the global population currently suffers from CKD and its complications. Given the increasing prevalence of CKD there is an urgent need to find novel treatment options. The American black bear (Ursus americanus) copes with months of lowered kidney function and metabolism during hibernation without the devastating effects on metabolism and other consequences observed in humans. In a biomimetic approach to better understand kidney adaptations and physiology in hibernating black bears, we established a high-quality genome assembly. Subsequent RNA-Seq analysis of kidneys comparing gene expression profiles in black bears entering (late fall) and emerging (early spring) from hibernation identified 169 protein-coding genes that were differentially expressed. Of these, 101 genes were downregulated and 68 genes were upregulated after hibernation. Fold changes ranged from 1.8-fold downregulation (RTN4RL2) to 2.4-fold upregulation (CISH). Most notable was the upregulation of cytokine suppression genes (SOCS2, CISH, and SERPINC1) and the lack of increased expression of cytokines and genes involved in inflammation. The identification of these differences in gene expression in the black bear kidney may provide new insights in the prevention and treatment of CKD