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We present an experimental study of the effect of layer interfaces on the x-ray reflectance in Cr/B4C multilayer interference coatings with layer thicknesses ranging from 0.7 nm to 5.4 nm. The multilayers were deposited by magnetron sputtering and by ion beam sputtering. Grazing incidence x-ray reflectometry, soft x-ray reflectometry, and transmission electron microscopy reveal asymmetric multilayer structures with a larger B4C-on-Cr interface, which we modeled with a 1-1.5 nm thick interfacial layer. Reflectance measurements in the vicinity of the Cr L2,3 absorption edge demonstrate fine structure that is not predicted by simulations using the currently tabulated refractive index (optical constants) values for Cr.

Consistent with the diversity of Latin America, there is profound variability in asthma burden among and within countries in this region. Regional variation in asthma prevalence is likely multifactorial and due to genetics, perinatal exposures, diet, obesity, tobacco use, indoor and outdoor pollutants, psychosocial stress and microbial or parasitic infections. Similarly, non-uniform progress in asthma management leads to regional variability in disease morbidity. Future studies of distinct asthma phenotypes should follow-up well-characterised Latin American subgroups and examine risk factors that are unique or common in Latin America (eg, stress and violence, parasitic infections and use of biomass fuels for cooking). Because most Latin American countries share the same barriers to asthma management, concerted and multifaceted public health and research efforts are needed, including approaches to curtail tobacco use, campaigns to improve asthma treatment, broadening access to care and clinical trials of non-pharmacological interventions (eg, replacing biomass fuels with gas or electric stoves). [ABSTRACT FROM AUTHOR]

BACKGROUND Respiratory syncytial virus (RSV) infection causes considerable illness in older adults. The efficacy and safety of an investigational bivalent RSV prefusion F protein—based (RSVpreF) vaccine in this population are unknown. METHODS In this ongoing, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults (260 years of age) to receive a single intramuscular injection of RSVpreF vaccine at a dose of 120 pg (RSV subgroups A and B, 60 itg each) or placebo. The two primary end points were vaccine efficacy against seasonal RSV-associated lower respiratory tract illness with at least two or at least three signs or symptoms. The secondary end point was vaccine efficacy against RSV-associated acute respiratory illness. RESULTS At the interim analysis (data-cutoff date, July 14, 2022), 34,284 participants had received RSVpreF vaccine (17,215 participants) or placebo (17,069 participants). RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 participants in the vaccine group (1.19 cases per 1000 person-years of observation) and 33 participants in the placebo group (3.58 cases per 1000 person-years of observation) (vaccine efficacy, 66.7%; 96.66% confidence interval [CI], 28.8 to 85.8); 2 cases (0.22 cases per 1000 person-years of observation) and 14 cases (1.52 cases per 1000 person-years of observation), respectively, occurred with at least three signs or symptoms (vaccine efficacy, 85.7%; 96.66% CI, 32.0 to 98.7). RSV-associated acute respiratory illness occurred in 22 participants in the vaccine group (2.38 cases per 1000 person-years of observation) and 58 partici-pants in the placebo group (6.30 cases per 1000 person-years of observation) (vac-cine efficacy, 62.1%; 95% CI, 37.1 to 77.9). The incidence of local reactions was higher with vaccine (12%) than with placebo (7%); the incidences of systemic events were similar (27% and 26%, respectively). Similar rates of adverse events through 1 month after injection were reported (vaccine, 9.0%; placebo, 8.5%), with 1.4% and 1.0%, respectively, considered by the investigators to be injection-related. Severe or life-threatening adverse events were reported in 0.5% of vaccine recipients and 0.4% of placebo recipients. Serious adverse events were reported in 2.3% of participants in each group through the data-cutoff date. CONCLUSIONS RSVpreF vaccine prevented RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness in adults (260 years of age), without evident safety concerns. (Funded by Pfizer; RENOIRClinicalTrials.gov number, NCT05035212; EudraCT number, 2021-003693-31.) [ABSTRACT FROM AUTHOR]

Background: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine.Methods: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases.Results: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%).Conclusions: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.). [ABSTRACT FROM AUTHOR]

Background: BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable.Methods: In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory-confirmed Covid-19 and safety, which were both evaluated through 6 months after vaccination.Results: BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few participants had adverse events leading to withdrawal from the trial. Vaccine efficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2) through 6 months of follow-up among the participants without evidence of previous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in populations with diverse ages, sexes, race or ethnic groups, and risk factors for Covid-19 among participants without evidence of previous infection with SARS-CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was predominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed.Conclusions: Through 6 months of follow-up and despite a gradual decline in vaccine efficacy, BNT162b2 had a favorable safety profile and was highly efficacious in preventing Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.). [ABSTRACT FROM AUTHOR]

Most strategies for reducing global measles morbidity and mortality and eliminating measles are based on the ability to enhance immune responses to measles virus. Challenges to measles elimination and eradication are based in part on the need to sustain high levels of population immunity to interrupt transmission of measles virus. We review aspects of the immunology of measles and measles vaccination with the aim of demonstrating how knowledge of the immune responses is essential to furthering the goals of reducing measles morbidity and mortality and the elimination of measles. Better understanding of the mechanisms of immune suppression after measles, the potential for alternative vaccination strategies to induce immunity in young infants, and the immunologic basis of atypical measles, increased mortality after high-titer measles vaccine, and waning immunity will lead to improved strategies for measles control and elimination.

Objective: Children with HIV infection are particularly susceptible to invasive pneumococcal disease, yet the effect of HIV infection and its medical management on colonization and resistance to antibiotics are poorly described. To provide a basis for medical practice, we determined the prevalence of nasopharyngeal colonization and antibiotic resistance of Streptococcus pneumoniae in children with HIV infection., Methods: Cross-sectional prevalence sample of children attending the pediatric HIV and pulmonary clinics to examine nasopharyngeal colonization with S. pneumoniae and antibiotic resistance to beta-lactams and trimethoprim-sulfamethoxazole (T/S). Subjects were matched by age and date of clinic visit., Results: The colonization rate with S. pneumoniae of HIV-infected and -indeterminate children was equal to that of controls (20% vs. 19%). HIV infection, CDC staging or receipt of oral antibiotic therapy did not affect colonization. Isolates from HIV-infected and -indeterminate children were less likely to be penicillin-resistant than those from controls (18% vs. 50%). There was no difference in pneumococcal resistance to T/S among isolates from subjects and controls, despite 72% T/S use in the HIV clinic., Conclusion: Colonization with S. pneumoniae in HIV disease is no different from that of comparable children. The high incidence of pneumococcal disease and prophylaxis with T/S are not related to nasopharyngeal colonization. Antibiotic prophylaxis of HIV-infected children does not necessarily lead to increased resistance of S. pneumoniae.

Measles remains a principal cause of worldwide mortality, in part because young infants cannot be immunized effectively. Development of new vaccines has been hindered by previous experience with a formalin-inactivated vaccine that predisposed to a severe form of disease (atypical measles). Here we have developed and tested potential DNA vaccines for immunogenicity, efficacy and safety in a rhesus macaque model of measles. DNA protected from challenge with wild-type measles virus. Protection correlated with levels of neutralizing antibody and not with cytotoxic T lymphocyte activity. There was no evidence in any group, including those receiving hemagglutinin-encoding DNA alone, of 'priming' for atypical measles.

The purpose of the study was to establish the frequency of, reasons for, and outcome of formula changes in infants. In this survey, we interviewed a convenience sample of 100 parents in our pediatric outpatient clinic and 75 parents in private pediatric office practices regarding their baby's initial formula, changes in formula, age at change, reason for change, initiator of the change, and outcome. The infants were 30-210 days old. Sixteen of the 175 infants (9%) were started on nonstandard formulas at birth. Fifty-eight of the remaining 159 infants (36%) were changed from regular to nonstandard formulas. After using nonstandard formulas, only seven infants (4%) were ever challenged subsequently with regular formula and all did well. Colic and regurgitation were the main reasons for switching formulas. In 47% the decision to change the formula was made by the mother and in 44% by the pediatrician. Following the formula change, mothers reported improvement or complete resolution of symptoms in 80% of infants. Although published estimates of formula intolerance range from 2% to 7.5%, one in three infants experiences a formula change, suggesting that nonstandard formulas are used excessively by both mothers and physicians. Nevertheless, in the vast majority of cases, parents report that the changes result in improvement or resolution of symptoms. Thus, while this practice appears to be a simple and effective intervention, it produces a significant population of soy and other nonstandard formula-fed babies who should be drinking regular formulas. Such changes encourage a belief by parents that their infants are allergic or otherwise abnormal and could have a negative impact on subsequent child development.

The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and fusion-inhibiting antibodies, but no cytotoxic T-cell response. Subsequent infection with measles virus caused an atypical rash and pneumonitis, accompanied by immune complex deposition and an increase in eosinophils. Fusion-inhibiting antibody appeared earlier in these monkeys than in non-immunized monkeys. These data indicate that atypical measles results from previous priming for a nonprotective type 2 CD4 T-cell response rather than from lack of functional antibody against the fusion protein.