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Background We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses. Methods Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18–64 years for H10N8 study; 18–49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 µg and intradermal dose levels of 25 and 50 µg were evaluated. H7N9 IM 10-, 25-, and 50-µg dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay). Results H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-µg IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-µg intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 µg achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-µg groups and 96.6% in the 50-µg group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 µg IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 µg). Significant cell-mediated responses were not detected in either study. Conclusions The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses. ClinicalTrials.gov NCT03076385 and NCT03345043 .

Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles., Potential pandemic influenzas and the need for an effective, safe, and high-speed vaccine production platform have been widely discussed in the scientific community. Bahl et al. report the rapid and robust immune responses achieved against H10N8 and H7N9 viruses from modified mRNA vaccines with an acceptable safety profile.

The purpose of this research was to verify that various segments of the rock climbing community have different attitudes toward resource management and to aid in the understanding of attitudinal differences that can affect rock-climbing management. Respondents were given an on-site questionnaire; 400 usable surveys were collected from 13 different locations in the United States. Respondents identified themselves according to the type of climbing they participated in (e.g., traditional climbing, sport climbing, and hybrid climbing). Factor analysis identified five usable factors: bolt placement/use, need for management, reservations about management, appropriateness of bolts, and climbers' self-perception. A repeated-measures analysis of variance identified significant differences among responses from traditional and sport climbers on four of the five scales used to measures attitudes. The variance among the climbing subgroups indicated that various climbing groups had significantly different attitudes toward management. All climbers surveyed had reservations about the management process. Results from the analysis indicated that climbers from all three groups (traditional, sport, and hybrid) felt that managers did not adequately understand the activity of climbing, climbers did not adequately understand the management process, climbing was not treated fairly in the management process in comparison to other activities, and climbing was micromanaged.

Children aged 3 and 4 were asked to name from memory items belonging in a house. Experimental groups completed the task twice, under two conditions. In the function-context condition, the experimenter provided a verbal description of use in response to each item named. In the objectcontext condition, the child was given a miniature replica of each item named. A control group at each age received only general encouragement for each response. Results indicated that the function context was more facilitative to retrieval than was the object context, which did not differ in effect from the control condition. Function context also had major effects on the types of items retrieved: More room items and fewer people and animals were produced in the functioncontext condition than in the other conditions. The representation of function and action in early conceptual schemes is discussed.

Case studies of “boom towns” in the western United States and the theory of social disorganization predict positive effects of recent growth and energy development on the violent crime rate in small towns and rural areas. Regression results, with controls for local characteristics prior to the energy boom of the 1970s, give little evidence of additive effects of recent growth and energy development on the violent crime rate in nonmetropolitan counties of the major energy-producing states. Long-standing structural problems are better predictors of the violent crime rate than are recent changes associated with energy development.

The assumption that energy development causes social disruption in western communities is based on undocumented assertions, questionable interpretations of evidence, and superficial analyses. Theor...

A positive association between change in the divorce rate and net inmigration [in the United States] has been suggested in discussions of recent rural population growth particularly in areas affected by rapid development of energy resources. Previous research findings suggest that the divorce rate is affected by stress and by effectiveness of constraints to divorce and that these might be influenced by net inmigration. Data on change in divorce rates of 292 counties of the Old West region from 1970 to 1975 were examined. Multiple regression results indicate that new inmigration had little effect on change in the divorce rate. (EXCERPT)