Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico.

BACKGROUND: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).

Efficient matrix approach to optical wave propagation and Linear Canonical Transforms.

The Fresnel diffraction integral form of optical wave propagation and the more general Linear Canonical Transforms (LCT) are cast into a matrix transformation form. Taking advantage of recent efficient matrix multiply algorithms, this approach promises an efficient computational and analytical tool that is competitive with FFT based methods but offers better behavior in terms of aliasing, transparent boundary condition, and flexibility in number of sampling points and computational window sizes of the input and output planes being independent. This flexibility makes the method significantly faster than FFT based propagators when only a single point, as in Strehl metrics, or a limited number of points, as in power-in-the-bucket metrics, are needed in the output observation plane.

Signal-to-noise ratio limitations for intensity correlation imaging.

Intensity correlation imaging (ICI) is a concept which has been considered for the task of providing images of satellites in geosynchronous orbit using ground-based equipment. This concept is based on the intensity interferometer principle first developed by Hanbury Brown and Twiss. It is the objective of this paper to establish that a sun-lit geosynchronous satellite is too faint a target object to allow intensity interferometry to be used in developing image information about it-at least not in a reasonable time and with a reasonable amount of equipment. An analytic treatment of the basic phenomena is presented. This is an analysis of one aspect of the statistics of the very high frequency random variations of a very narrow portion of the optical spectra of the incoherent (black-body like-actually reflected sunlight) radiation from the satellite, an analysis showing that the covariance of this radiation as measured by a pair of ground-based telescopes is directly proportional to the square of the magnitude of one component of the Fourier transform of the image of the satellite-the component being the one for a spatial frequency whose value is determined by the separation of the two telescopes. This analysis establishes the magnitude of the covariance. A second portion of the analysis considers shot-noise effects. It is shown that even with much less than one photodetection event (pde) per signal integration time an unbiased estimate of the covariance of the optical field's random variations can be developed. Also, a result is developed for the standard deviation to be associated with the estimated value of the covariance. From these results an expression is developed for what may be called the signal-to-noise ratio to be associated with an estimate of the covariance. This signal-to-noise ratio, it turns out, does not depend on the measurement's integration time, Δt (in seconds), or on the optical spectral bandwidth, Δν (in Hertz), utilized-so long as ΔtΔν≫1, which condition it would be hard to violate. It is estimated that for a D=3.16 m diameter satellite, with a pair of D=1.0 m diameter telescopes (which value of D probably represents an upper limit on allowable aperture diameter since the telescope aperture must be much too small to even resolve the size of the satellite) at least N=2.55×10(16) separate pairs of (one integration time, pde count) measurement values must be collected to achieve just a 10 dB signal-to-noise ratio. Working with 10 pairs of telescopes (all with the same separation), and with 10 nearly adjacent and each very narrow spectral bands extracted from the light collected by each of the telescope-so that for each measurement integration time there would be 100 pairs of measurement values available-and with an integration time as short as Δt=1 ns, it would take T=2.55×10(5) s or about 71 h to collect the data for just a single spatial frequency component of the image of the satellite. It is on this basis that it is concluded that the ICI concept does not seem likely to be able to provide a timely responsive capability for the imaging of geosynchronous satellites.

Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age.

BACKGROUND: This clinical trial examined the safety and immunogenicity of annual revaccination with Fluzone(®) Intradermal (Sanofi Pasteur, Swiftwater, PA) vaccine compared to a standard intramuscular (IM) split-virion trivalent influenza vaccine (Fluzone(®), Sanofi Pasteur). METHODS: This phase II, active-controlled, multi-centre, open-label trial was conducted in 2009 and 2010, and enrolled 1250 adults 18-64 years of age who were randomly selected from participants in a phase III influenza vaccine trial the previous year (NCT00772109). Subjects who had previously received the ID vaccine were randomized 2:1 to be revaccinated with the ID or IM vaccine and those who previously received the IM vaccine were randomized 1:1. Solicited reactions were recorded on the day of vaccination and continuing for the next 7 days, non-serious adverse events for 28 days, and serious adverse events for 6 months after vaccination. Hemagglutination inhibition antibody titres were assessed pre-vaccination and at day 28. RESULTS: Reactions were well-tolerated and resolved in the first 7 days, but erythema, induration, swelling, pruritus and ecchymosis were reported by more subjects receiving the ID vaccine than the IM vaccine. Compared to receipt of IM vaccine in the previous year, ID vaccine in the previous year led to statistically higher rates of erythema, swelling and induration after IM vaccine in the second year. Injection-site pain and systemic reactions did not differ between ID and IM vaccines. No treatment-related serious adverse events were reported. Geometric mean antibody titres, seroprotection rates, and seroconversion rates were non-inferior for the ID and IM vaccines for all three viral strains. CONCLUSIONS: The ID vaccine was as immunogenic as the IM vaccine, and raised no safety concerns. It can be used interchangeably with the IM vaccine for annual revaccination in adults 18-64 years of age in consecutive years without safety concerns.

Extruding Kolmogorov-type phase screen ribbons.

A phase screen ribbon extrusion process is presented that allows a phase screen ribbon of any specified width to be extruded, one column at a time, producing a ribbon of any desired length, with Kolmogorov statistics (i.e., having a five-thirds power-law-dependent structure function) for all separations up to some selected upper limit--which upper limit can be as large as desired. The method is an adaptation of the method described by [Assémat et al. Opt. Express 14, 988 (2006)].

Optimal control of laser beams for propagation through a turbulent medium.

Concerning the problem of transmitting a laser beam from one telescope to another telescope through a turbulent medium, it is established that using an adaptive optical system on both telescopes to precompensate an outgoing laser beam based on the aberrations measured on the received laser beam leads to an iteration that maximizes the transmission (neglecting attenuation losses) of laser power between the telescopes. Simulation results are presented demonstrating the effectiveness of this technique when the telescopes are equipped with either phase-only or full-wave compensation systems. Simulation results are shown that indicate that for a uniform distribution of the strength of turbulence, 95% transmission of laser power is attained when both telescopes can achieve full-wave compensation provided that the aperture diameter D of the two telescopes is greater than twice the Fresnel length square root of lambdaL, where A is the wavelength of propagation and L is the distance between the two telescopes.

Evaluation of the performance of a shearing interferometer in strong scintillation in the absence of additive measurement noise.

A simulation study is presented that evaluates the ability of a unit-shear, shearing interferometer to estimate a complex field resulting from propagation through extended turbulence. Performance is defined in terms of the Strehl ratio achieved when the estimate of the complex field obtained from reconstruction is used to correct the distorted wave front presented to the wave-front sensor. A series of evaluations is performed to identify the strengths and weaknesses of the shearing interferometer in the two-dimensional space of the Fried parameter r0 and the Rytov number. The performance of the shearing interferometer is compared with that of a Hartmann sensor in the Fried and Hutchin geometries. Although the effects of additive measurement noise (such as read noise, shot noise, amplifier noise) are neglected, the fundamental characteristics of the measurement process are shown to distinguish the performance of the various wave-front sensors. It is found that the performance of a shearing interferometer is superior to that of a Hartmann sensor when the Rytov number exceeds 0.2.

Evaluation of the performance of Hartmann sensors in strong scintillation.

A simulation study is presented that evaluates the performance of Hartmann wave-front sensors with measurements obtained with the Fried geometry and the Hutchin geometry. Performance is defined in terms of the Strehl ratio achieved when the estimate of the complex field obtained from reconstruction is used to correct the distorted wave front presented to the wave-front sensor. A series of evaluations is performed to identify the strengths and the weaknesses of Hartmann sensors used in each of the two geometries in the two-dimensional space of the Fried parameter r0 and the Rytov parameter. We found that the performance of Hartmann sensors degrades severely when the Rytov number exceeds 0.2 and the ratio l/r0 exceeds 1/4 (where l is the subaperture side length) because of the presence of branch points in the phase function and the effect of amplitude scintillation on the measurement values produced by the Hartmann sensor.