Background The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. Methods In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. Results A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. Conclusions AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746 .)

Background Respiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality. This Phase I, randomized, observer-blind, placebo- and active-controlled study evaluated an investigational vaccine against RSV (ChAd155-RSV) using the viral vector chimpanzee-adenovirus-155, encoding RSV fusion (F), nucleocapsid, and transcription antitermination proteins. Methods Healthy 18–45-year-old adults received ChAd155-RSV, a placebo, or an active control (Bexsero) at Days (D) 0 and 30. An escalation from a low dose (5 × 109 viral particles) to a high dose (5 × 1010 viral particles) occurred after the first 16 participants. Endpoints were solicited/unsolicited and serious adverse events (SAEs), biochemical/hematological parameters, cell-mediated immunogenicity by enzyme-linked immunospot, functional neutralizing antibodies, anti RSV-F immunoglobin (Ig) G, and ChAd155 neutralizing antibodies. Results There were 7 participants who received the ChAd155-RSV low dose, 31 who received the ChAd155-RSV high dose, 19 who received the placebo, and 15 who received the active control. No dose-related toxicity or attributable SAEs at the 1-year follow-up were observed. The RSV-A neutralizing antibodies geometric mean titer ratios (post/pre-immunization) following a high dose were 2.6 (D30) and 2.3 (D60). The ratio of the fold-rise (D0 to D30) in anti-F IgG over the fold-rise in RSV-A–neutralizing antibodies was 1.01. At D7 after the high dose of the study vaccine, the median frequencies of circulating B-cells secreting anti-F antibodies were 133.3/106 (IgG) and 16.7/106 (IgA) in peripheral blood mononuclear cells (PBMCs). The median frequency of RSV-F–specific interferon γ–secreting T-cells after a ChAd155-RSV high dose was 108.3/106 PBMCs at D30, with no increase after the second dose. Conclusions In adults previously naturally exposed to RSV, ChAd155-RSV generated increases in specific humoral and cellular immune responses without raising significant safety concerns. Clinical Trials Registration NCT02491463.

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The uncertainties in the MTF calculation with the edge technique are larger than with the bar technique, and the differences increase with the frequency. On the one hand, the stronger dependency on the frequency shown by the standard deviation of the MTF makes the precision gets worse faster in the edge technique. On the other hand, in the case of the edge and for high levels of noise, differentiation produces line spread functions (LSF) with a poor SNR, increasing erroneously the MTF and worsening accuracy.

The small fields in radiotherapy are widely used due to the development of techniques such as intensity-modulated radiotherapy and stereotactic radio surgery. The measurement of the dose distributions for small fields is a challenge. A perfect dosimeter should be independent of the radiation energy and the dose rate and should have a negligible volume effect. The radiochromic (RC) film characteristics fit well to these requirements. However, the response of RC films and their digitizing processes present a significant spatial inhomogeneity problem. The present work uses a method for two-dimensional (2D) measurement with RC films based on the reduction of the spatial inhomogeneity of both the film and the film digitizing process. By means of registering and averaging several measurements of the same field, the inhomogeneities are mostly canceled. Measurements of output factors (OFs), dose profiles (in-plane and cross-plane), and 2D dose distributions are presented. The field sizes investigated are 0.5 × 0.5 cm2, 0.7 × 0.7 cm2, 1 × 1 cm2, 2 × 2 cm2, 3 × 3 cm2, 6 × 6 cm2, and 10 × 10 cm2 for 6 and 15 MV photon beams. The OFs measured with the RC film are compared with the measurements carried out with a PinPoint ionization chamber (IC) and a Semiflex IC, while the measured transversal dose profiles were compared with Monte Carlo simulations. The results obtained for the OFs measurements show a good agreement with the values obtained from RC films and the PinPoint and Semiflex chambers when the field size is greater or equal than 2 × 2 cm2. These agreements give confidence on the accuracy of the method as well as on the results obtained for smaller fields. Also, good agreement was found between the measured profiles and the Monte Carlo calculated profiles for the field size of 1 × 1 cm2. We expect, therefore, that the presented method can be used to perform accurate measurements of small fields.