More-than-national and less-than-global: The biochemical infrastructure of vaccine manufacturing

The recent efforts to mount an R&D response to public health emergencies of international concern have led to the formation of what we term a biochemical infrastructure of vaccine development and production. In principle, this infrastructure is expected not only to curtail existing pandemics but also anticipate and contain yet-to-emerge future threats. Critically, by nature of its geographical distribution and technical modularity, that infrastructure promises both to accelerate and expand access to essential medical tools, and in so doing, redress global health inequities. In practice, however, the biochemical infrastructure of vaccines remains highly uneven, fragmented and unjust. Moving beyond calls for ‘global health solidarity’, this paper examines the key actors, normative techniques and socio-technical assemblages, from viral platform technologies to intellectual property waivers and from accelerated regulatory pathways to advance market commitments, that serve to link ‘just-in-case’ and ‘just-in-time’ modalities of global health R&D. We argue that the biomedical infrastructure of vaccine development and production emerging in the wake of the COVID-19 pandemic is unfolding across an innovation ecosystem that is more-than-national and yet less-than global: a reconfiguration that may offer possibilities for a new, radically-overhauled, model of vaccine equity

Advantages of 3D time-of-flight range imaging cameras in machine vision applications

Machine vision using image processing of traditional intensity images is in wide spread use. In many situations environmental conditions or object colours or shades cannot be controlled, leading to difficulties in correctly processing the images and requiring complicated processing algorithms. Many of these complications can be avoided by using range image data, instead of intensity data. This is because range image data represents the physical properties of object location and shape, practically independently of object colour or shading. The advantages of range image processing are presented, along with three example applications that show how robust machine vision results can be obtained with relatively simple range image processing in real-time applications

Experiments with regulations & markets linking upstream tree plantations with downstream water users

Land-use change in upper catchments impact downstream water flows. As trees use large amounts of water the expansion of upstream plantations can substantially reduce water availability to downstream users. There can also be impacts on downstream salinity due to reduced dilution flows. In some jurisdictions afforestation requires the purchase of water rights from downstream holders, while in others it does not, effectively handing the water rights to the upstream landholders. We consider the economic efficiency and equity (profitability and distributional) consequences of upstream land use change in the presence of a water market under alternate property rights regimes and different salinity scenarios.experimental-economics, tree-plantations, environmental-services, urban, irrigation, stock & domestic, water use, land use,

Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo

Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX “coating” also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting

Distributed Simultaneous Localisation and Auto-Calibration using Gaussian Belief Propagation

We present a novel scalable, fully distributed, and online method for simultaneous localisation and extrinsic calibration for multi-robot setups. Individual a priori unknown robot poses are probabilistically inferred as robots sense each other while simultaneously calibrating their sensors and markers extrinsic using Gaussian Belief Propagation. In the presented experiments, we show how our method not only yields accurate robot localisation and auto-calibration but also is able to perform under challenging circumstances such as highly noisy measurements, significant communication failures or limited communication range.Comment: Published in IEEE Robotics and Automation Letters (RA-L) 202

Obesity and the food environment: income and ethnicity differences among people with diabetes: the Diabetes Study of Northern California (DISTANCE).

ObjectiveIt is unknown whether any association between neighborhood food environment and obesity varies according to individual income and/or race/ethnicity. The objectives of this study were to test whether there was an association between food environments and obesity among adults with diabetes and whether this relationship differed according to individual income or race/ethnicity.Research design and methodsSubjects (n = 16,057) were participants in the Diabetes Study of Northern California survey. Kernel density estimation was used to create a food environment score for each individual's residence address that reflected the mix of healthful and unhealthful food vendors nearby. Logistic regression models estimated the association between the modeled food environment and obesity, controlling for confounders, and testing for interactions between food environment and race/ethnicity and income.ResultsThe authors found that more healthful food environments were associated with lower obesity in the highest income groups (incomes 301-600% and >600% of U.S. poverty line) among whites, Latinos, and Asians. The association was negative, but smaller and not statistically significant, among high-income blacks. On the contrary, a more healthful food environment was associated with higher obesity among participants in the lowest-income group (<100% poverty threshold), which was statistically significant for black participants in this income category.ConclusionsThese findings suggest that the availability of healthful food environments may have different health implications when financial resources are severely constrained

Influence of shear-thinning blood rheology on the laminar-turbulent transition over a backward facing step

Cardiovascular diseases are the leading cause of death globally and there is an unmet need for effective, safer blood-contacting devices, including valves, stents and artificial hearts. In these, recirculation regions promote thrombosis, triggering mechanical failure, neurological dysfunction and infarctions. Transitional flow over a backward facing step is an idealised model of these flow conditions; the aim was to understand the impact of non-Newtonian blood rheology on modelling this flow. Flow simulations of shear-thinning and Newtonian fluids were compared for Reynolds numbers ( R e ) covering the comprehensive range of laminar, transitional and turbulent flow for the first time. Both unsteady Reynolds Averaged Navier–Stokes ( k − ω SST) and Smagorinsky Large Eddy Simulations (LES) were assessed; only LES correctly predicted trends in the recirculation zone length for all R e . Turbulent-transition was assessed by several criteria, revealing a complex picture. Instantaneous turbulent parameters, such as velocity, indicated delayed transition: R e = 1600 versus R e = 2000, for Newtonian and shear-thinning transitions, respectively. Conversely, when using a Re defined on spatially averaged viscosity, the shear-thinning model transitioned below the Newtonian. However, recirculation zone length, a mean flow parameter, did not indicate any difference in the transitional Re between the two. This work shows a shear-thinning rheology can explain the delayed transition for whole blood seen in published experimental data, but this delay is not the full story. The results show that, to accurately model transitional blood flow, and so enable the design of advanced cardiovascular devices, it is essential to incorporate the shear-thinning rheology, and to explicitly model the turbulent eddies

A Robot Web for Distributed Many-Device Localisation

We show that a distributed network of robots or other devices which make measurements of each other can collaborate to globally localise via efficient ad-hoc peer to peer communication. Our Robot Web solution is based on Gaussian Belief Propagation on the fundamental non-linear factor graph describing the probabilistic structure of all of the observations robots make internally or of each other, and is flexible for any type of robot, motion or sensor. We define a simple and efficient communication protocol which can be implemented by the publishing and reading of web pages or other asynchronous communication technologies. We show in simulations with up to 1000 robots interacting in arbitrary patterns that our solution convergently achieves global accuracy as accurate as a centralised non-linear factor graph solver while operating with high distributed efficiency of computation and communication. Via the use of robust factors in GBP, our method is tolerant to a high percentage of faults in sensor measurements or dropped communication packets.Comment: Published in IEEE Transactions on Robotics (TRO) 202

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

Onset of meiosis in the chicken embryo; evidence of a role for retinoic acid

Background: Meiosis in higher vertebrates shows a dramatic sexual dimorphism: germ cells enter meiosis and arrest at prophase I during embryogenesis in females, whereas in males they enter mitotic arrest during embryogenesis and enter meiosis only after birth. Here we report the molecular analysis of meiosis onset in the chicken model and provide evidence for conserved regulation by retinoic acid