COVID-19 hospitalization rates rise exponentially with age,inversely proportional to thymic T-cell production

Here, we report that COVID-19 hospitalization rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R² = 0.98). This mirrors the well-studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by methicillin-resistant Staphylococcus aureus, MERS-CoV, West Nile virus, Streptococcus pneumoniae and certain cancers, such as chronic myeloid leukaemia and brain cancers. In addition, the incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesized that the age dependence does not come from social-mixing patterns, i.e. that the probability of hospitalization given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalizations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have fewer contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of fewer contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49–75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age dependence of hospitalization rates is the probability of hospitalization given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.     

Evaluation of the effects of sodium chloride,potassium sorbate,nisin and lysozyme on the probability of growth of Clostridium sporogenes

The aim of this study was to evaluate the combined effect of salt (sodium chloride, 0–8% w/v), sorbate (potassium sorbate, 0–4.5% w/v), nisin (0–500 ppm) and lysozyme (0–500 ppm) on the survival of Clostridium sporogenes as a non‐toxigenic surrogate of Clostridium botulinum in terms of the probability of growth by using a central composite rotatable design. The results indicated that salt and sorbate were the most effective factors in preventing the growth of Cl. sporogenes in high‐moisture (>95%) and low‐acid conditions. The probability of growth of Cl. sporogenes in broth was reduced by combinations of salt and sorbate. Nisin and lysozyme had insignificant effects on the probability of growth of Cl. sporogenes (P > 0.05). Lysozyme individually and in combination with nisin had no inhibitory effect on Cl. sporogenes. Overall, the addition of sorbate and lysozyme may allow the salt concentration to be reduced while preventing growth.     

An efficient online mapping tool for finding the shortest feasible path for alternative-fuel vehicles

Infrastructure for fuel-cell and other alternative-fuel vehicles is lacking not only in the paucity of fuel stations, but also in inadequate web-based support to help drivers complete their trips via the few stations that do exist. In this paper, we present an online mapping tool for finding the shortest feasible path in a road network given the vehicle's driving range and station locations. Users input their origin, destination, type of fuel, and driving range, and the algorithm generates a new reduced feasible network in which the vertices are the origin and destination nodes and reachable fuel stations and the edges represent feasible paths between them. Dijkstra's shortest path algorithm is applied to this reduced network to find the shortest feasible path. Efficiency is substantially improved by preprocessing and storing the shortest-path distances between stations. We present a web-mapping prototype (www.afvrouting.com) for hydrogen and compressed natural gas stations in the United States. Sample results illustrate the need for this kind of globally optimal solution method by showing that the optimal feasible path and refueling stops can vary tremendously as a result of user inputs for driving range, initial tank level, and one-way or round-trip.     

Overcoming Radiation Resistance in Gliomas by Targeting Metabolism and DNA Repair Pathways

Gliomas represent a wide spectrum of brain tumors characterized by their high invasiveness, resistance to chemoradiotherapy, and both intratumoral and intertumoral heterogeneity. Recent advances in transomics studies revealed that enormous abnormalities exist in different biological layers of glioma cells, which include genetic/epigenetic alterations, RNA expressions, protein expression/modifications, and metabolic pathways, which provide opportunities for development of novel targeted therapeutic agents for gliomas. Metabolic reprogramming is one of the hallmarks of cancer cells, as well as one of the oldest fields in cancer biology research. Altered cancer cell metabolism not only provides energy and metabolites to support tumor growth, but also mediates the resistance of tumor cells to antitumor therapies. The interactions between cancer metabolism and DNA repair pathways, and the enhancement of radiotherapy sensitivity and assessment of radiation response by modulation of glioma metabolism are discussed herein.     

Modulation of Mechanical Interactions by Local Piezoelectric Effects

Piezoelectricity is a well‐established property of biological materials, yet its functional role has remained unclear. Here, a mechanical effect of piezoelectric domains resulting from collagen fibril organisation is demonstrated, and its role in tissue function and application to material design is described. Using a combination of scanning probe and nonlinear optical microscopy, a hierarchical structuring of piezoelectric domains in collagen‐rich tissues is observed, and their mechanical effects are explored in silico. Local electrostatic attraction and repulsion due to shear piezoelectricity in these domains modulate fibril interactions from the tens of nanometre (single fibril interactions) to the tens of micron (fibre interactions) level, analogous to modulated friction effects. The manipulation of domain size and organisation thus provides a capacity to tune energy storage, dissipation, stiffness, and damage resistance.     

One-trial cocaine-induced behavioral sensitization in preweanling rats: Role of contextual stimuli.

Using a one-trial procedure, preweanling rats exhibit robust sensitization regardless of whether drug pretreatment and testing occur in the same or different environments. The purpose of the present study was to determine whether one-trial context-specific and context-independent sensitization of preweanling rats could be dissociated by varying the pretreatment dose of cocaine, by varying the pretreatment drug, or by minimizing interoceptive cues. In Experiments 1a and 1b, rats were pretreated with a broad dose range of cocaine (0–40 mg/kg) before placement in a novel activity chamber or the home cage. In Experiment 2, rats were pretreated with a locomotor-enhancing drug (e.g., methylphenidate, U50,488, or MK-801) before placement in a novel activity or anesthesia chamber. In Experiment 3, rats were anesthetized with isoflurane before cocaine administration to minimize the effects of interoceptive and injection cues. In all experiments, rats were challenged with cocaine on the test day (24 hr later), with locomotion being measured in activity chambers. Results showed that (a) the pretreatment dose of cocaine (10–40 mg/kg) did not differentially affect context-specific and context-independent sensitization; (b) cross-sensitization between methylphenidate and cocaine was observed in the context-specific condition, but not when using a context-independent procedure; and (c) sensitization was evident if injection and interoceptive cues were minimized. One possibility is that associative processes do not modulate the one-trial sensitization of preweanling rats. Alternatively, “unitization” may cause preweanling rats to treat the different environments as equivalent, thus permitting robust sensitization even when drug pretreatment and testing occur in different environments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)