Crowding and the shape of COVID-19 epidemics

The coronavirus disease 2019 (COVID-19) pandemic is straining public health systems worldwide, and major non-pharmaceutical interventions have been implemented to slow its spread1,2,3,4. During the initial phase of the outbreak, dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was primarily determined by human mobility from Wuhan, China5,6. Yet empirical evidence on the effect of key geographic factors on local epidemic transmission is lacking7. In this study, we analyzed highly resolved spatial variables in cities, together with case count data, to investigate the role of climate, urbanization and variation in interventions. We show that the degree to which cases of COVID-19 are compressed into a short period of time (peakedness of the epidemic) is strongly shaped by population aggregation and heterogeneity, such that epidemics in crowded cities are more spread over time, and crowded cities have larger total attack rates than less populated cities. Observed differences in the peakedness of epidemics are consistent with a meta-population model of COVID-19 that explicitly accounts for spatial hierarchies. We paired our estimates with globally comprehensive data on human mobility and predict that crowded cities worldwide could experience more prolonged epidemics

Targeting a Newly Established Spontaneous Feline Fibrosarcoma Cell Line by Gene Transfer

Fibrosarcoma is a deadly disease in cats and is significantly more often located at classical vaccine injections sites. More rare forms of spontaneous non-vaccination site (NSV) fibrosarcomas have been described and have been found associated to genetic alterations. Purpose of this study was to compare the efficacy of adenoviral gene transfer in NVS fibrosarcoma. We isolated and characterized a NVS fibrosarcoma cell line (Cocca-6A) from a spontaneous fibrosarcoma that occurred in a domestic calico cat. The feline cells were karyotyped and their chromosome number was counted using a Giemsa staining. Adenoviral gene transfer was verified by western blot analysis. Flow cytometry assay and Annexin-V were used to study cell-cycle changes and cell death of transduced cells. Cocca-6A fibrosarcoma cells were morphologically and cytogenetically characterized. Giemsa block staining of metaphase spreads of the Cocca-6A cells showed deletion of one of the E1 chromosomes, where feline p53 maps. Semi-quantitative PCR demonstrated reduction of p53 genomic DNA in the Cocca-6A cells. Adenoviral gene transfer determined a remarkable effect on the viability and growth of the Cocca-6A cells following single transduction with adenoviruses carrying Mda-7/IL-24 or IFN-γ or various combination of RB/p105, Ras-DN, IFN-γ, and Mda-7 gene transfer. Therapy for feline fibrosarcomas is often insufficient for long lasting tumor eradication. More gene transfer studies should be conducted in order to understand if these viral vectors could be applicable regardless the origin (spontaneous vs. vaccine induced) of feline fibrosarcomas

Antarctic surface reflectivity calculations and measurements from the ANITA-4 and HiCal-2 experiments

The balloon-borne HiCal radio-frequency (RF) transmitter, in concert with the ANITA radio-frequency receiver array, is designed to measure the Antarctic surface reflectivity in the RF wavelength regime. The amplitude of surface-reflected transmissions from HiCal, registered as triggered events by ANITA, can be compared with the direct transmissions preceding them by O ( 10 ) microseconds, to infer the surface power reflection coefficient R . The first HiCal mission (HiCal-1, Jan. 2015) yielded a sample of 100 such pairs, resulting in estimates of R at highly glancing angles (i.e., zenith angles approaching 90°), with measured reflectivity for those events which exceeded extant calculations [P. W. Gorham et al., Journal of Astronomical Instrumentation, 1740002 (2017)]. The HiCal-2 experiment, flying from December 2016–January 2017, provided an improvement by nearly 2 orders of magnitude in our event statistics, allowing a considerably more precise mapping of the reflectivity over a wider range of incidence angles. We find general agreement between the HiCal-2 reflectivity results and those obtained with the earlier HiCal-1 mission, as well as estimates from Solar reflections in the radio-frequency regime [D. Z. Besson et al., Radio Sci. 50, 1 (2015)]. In parallel, our calculations of expected reflectivity have matured; herein, we use a plane-wave expansion to estimate the reflectivity R from both a flat, smooth surface (and, in so doing, recover the Fresnel reflectivity equations) and also a curved surface. Multiplying our flat-smooth reflectivity by improved Earth curvature and surface roughness corrections now provides significantly better agreement between theory and the HiCal-2 measurements

Investigation of PEGylated Derivatives of Rosin as Sustained Release Film Formers

The purpose of the present study was to investigate the potential use of two PEGylated derivatives of rosin (PD) as sustained release film forming materials. The derivatives differed chemically by their acid numbers—PD-1 with 120.93 and PD-2 with 88.19. The derivative films were characterized for surface morphology, water uptake-weight loss, angle of contact, water vapor transmission rate, mechanical properties and permeability study. Dissolution of diclofenac sodium (DS) and propranolol hydrochloride (PHL) as model drugs was studied from coated pellets. The films of derivatives with and without plasticizers were smooth and continuous. PD-2 films developed greater numbers of pores when in contact with phosphate buffer pH 6.8. The low weight loss, low angles of contact and high water vapor transmission rate of PD-2 films were related to presence of higher concentration of PEG esters. Higher tensile strength and percent elongation of PD-2 films was due to greater degree of internal plasticization of the derivative. The permeability of films to model drugs propranolol hydrochloride and diclofenac sodium was inversely proportional to the film thickness and dibutyl phthalate concentration in them; the permeability being greatest in PD-2 films containing 10% PEG 200. Dissolution rate of propranolol hydrochloride was higher from the coated pellets. The dissolution data followed zero order, Baker–Lonsdale equation and Hixon–Crowell equation of release kinetics with high correlation coefficients. The mechanism of drug release from these coated systems however followed class II transport (n > 1.0). The derivatives investigated could successfully retard release of the model drugs and offers an alternative to the conventionally used polymers

PEGylated rosin derivatives: Novel microencapsulating materials for sustained drug delivery

The aim of this study was to investigate PEGylated rosin derivatives (PRDs) as microencapsulating materials for sustained drug delivery. PRDs (D1, D2, and D3) composed of a constant weight of rosin and varied amounts of polyethylene glycol (PEG) 400 and maleic anhydride were synthesized in the laboratory. Microparticles were prepared by the O/O solvent evaporation technique using the acetone/paraffin system. Diclofenac sodium (DFS) and diltiazem hydrochloride (DLTZ) were used as model drugs. The effect of the type of PRD, drug, PRD:drug ratio, viscosity of external phase, stirring speed, concentration of magnesium stearate (droplet stabilizer), and method of preparation on particle size, drug loading, and drug release profiles of microparticles was investigated. PRDs could produce discrete and spherical microspheres (with DFS) and microcapsules (with DLTZ). The drug loading value for microparticles was found to be in the range of 37.21% to 87.90%. The microparticle size range was 14 to 36 μm. The particle size and drug loadings of microparticles were substantially affected by the concentration of magnesium stearate and the type of drug, respectively. Most of the formulations could sustain the DFS and DLTZ release for 20 hours. DFS and DLTZ release from PRD microparticles followed Hixson-Crowell and first-order kinetics, respectively. The results suggest that PRDs can be used successfully to prepare discrete and spherical microparticles with DFS and DLTZ for sustained drug delivery