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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.

This article reports the findings of a case study of a major California water management district's effort to change its management approach. The following key findings and factors have influenced the Salinas basin management plan (BMP) and its progress: (1) the Salinas Valley is an economy dominated by highly sophisticated irrigated agriculture dependent on ground water; (2) a persistent pattern of agricultural overdraft of ground water has hurt growers primarily in the north end of the valley via induced saline intrusion of irrigation wells; (3) a complex set of water institutions, property and water rights, and land lease practices offer little incentive for good stewardship of land and water; and (4) the BMP approach initially may have intensified tension among growers and between growers and other water user groups. Water rules and practices in the Salinas Valley and Monterey County have evolved through a long historical process of adaptations. Therefore, any significant changes in local water use practices need to be understood in terms of cultural change, that is, changes in deeply held values, beliefs, and assumptions. We believe the BMP and the MCWRA are succeeding when evaluated from this evolutionary perspective. The fact that both still exist relatively intact testifies that they are working, albeit slowly.

The power of computers has increased in recent decades, and one might expect improved management to result because decisions can be made with understanding available only via models. However, there is potential for quite the opposite: poor decisions due to unrealistic model output generated by users without access to appropriate training in the use of models. We discuss and, by reference to water demand models (IWR-MAIN, MWD-MAIN), illustrate three areas in which unintended errors of judgment by untrained personnel may cause difficulty: * Attributes of management models; if output from any type of model has no measure of confidence, then results may be over- or undervalued * Input data; with complex models, problems here typically will be difficult to detect. * Calibration and history-matching (verification); if these steps or data are combined, then users should be less trustful of model output than otherwise. Because all models have weaknesses and because there always is uncertainty about output from any model, we end with suggestions for coping with complex models. Monitoring programs play a central role in such efforts because they can identify discrepancies between model predictions and actual events and because they can ensure time is available to develop solutions for problems unanticipated in the modeling effort.

This paper reviews the processes that occurred during an application of the Metropolitan Water District (MWD)-MAIN water use forecasting system for the City of Salinas, California. The review includes an analysis of sources of available data, methods for estimating input data, calibration, and verification of the MWD-MAIN System, and an evaluation of the reliability of system output. We found that inexperienced users can have difficulty understanding the level of skill, knowledge, and amount of data that are required to produce reliable forecasts. Some of the issues associated with application of the MWD-MAIN System include the following: • All input data needed for accurate forecasts simply are not available for many cities and towns. • The data requirements are more extensive than many users anticipate. • Substantial requirements for manipulation of input data produces opportunity for error that creates major time demands in troubleshooting. • Calibration and verification for specific uses can be substantially more difficult than is readily apparent from the guidance manual. • Independent validity checks need to be done to validate system output. • If specified calibrating procedures do not produce reasonable results, reestimating slope coefficients is an option, but this requires resources and expertise that can easily exceed the limits of most users. These are problems typical of most complex models. Reviews such as this can help users to appreciate the level of data required, and to use the MWD-MAIN System in a more effective and efficient manner.

Efforts to reintroduce the wolf to the greater Yellowstone ecosystem were stalled again in 1991 when Congress rejected the recommendations of the Wolf Management Committee (WMC). I suggest that wolf reintroduction is a difficult policy problem, in part, because the human dimensions of the problem are difficult to assess and manage. Estimates of livestock depredation used by the WMC are analyzed to illustrate how they can be interpreted as incorrect and antagonistic by some stakeholders. Alternative estimates of livestock depredation and costs of compensation are presented. It is argued that what is important about such estimates is the process by which they are developed. Federal agencies working toward wolf recovery need to recognize that wolf reintroduction is a “stalking horse”; for the larger issue of land use change in the greater Yellowstone ecosystem. Therefore, wolf reintroduction needs to be treated as a major policy conflict. A state‐of‐the‐art environmental impact statement is now unde...

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.

Obstetrical health care resources have been declining in rural areas since 1980, resulting in reduced prenatal care that can result in higher medical costs. Loss of health care services is known to have negative economic consequences for rural communities. This article illustrates how hospitals and other providers of medical services can be used as vehicles for local economic development. Provision of medical services is an important component of the economic base of all communities and especially of small rural communities with hospitals. When a community loses medical services to another community, it loses both direct and indirect economic benefits. The research presented here analyzes the economic effects of outmigration of obstetric services from a rural “perimeter” community in Wyoming. The combined direct and indirect economic losses are shown to be significant. Annual revenue losses to the local hospital were estimated as high as 12 percent. It is important to make explicit the economic losses that result from reductions in health care. Such research, combined with knowledge of negative health and social factors can provide community leaders with additional motivation to find solutions to declining health care in rural areas.

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.

Sociopsychological variables, including attitudes, beliefs, values, and opinions, occupy a central place in emerging social impact assessment methodologies. Despite the attention that these perceptual concepts have received in the Social Impact Assessment (SIA) literature, there is little consensus on how they should be used. Four critical issues influence the utility of attitudes in the SIA process: (1) the location of attitudes in SIA research models, (2) the ubiquitous problem of attitude‐behavior predictability, (3) the “other variables”; problem, and (4) the measurement problem, i.e., the importance of measurement validity, reliability, and scalability. The authors first review the use of attitudes and perceptual measures in the SIA literature. This review reveals that while almost all authors of SIA models or methodologies recommend the inclusion of sociopsychological measures, the manner in which they propose these measures for use varies widely with most authors failing to specify whether...

(1988). Political and Athletic Interaction in Athens during the Sixth and Fifth Centuries B.C. Research Quarterly for Exercise and Sport: Vol. 59, No. 3, pp. 183-190.

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.

Although numerous, small, manganese oxide deposits associated with dolomite in the Eastern Transvaal escarpment, Republic of South Africa, have been known for many years, their mineralogical make-up is somewhat controversial. Chemical, mineralogical, and morphological properties of the weathering products of dolomite and the coexisting manganese oxide material in the Graskop area were therefore determined. Mn and Fe occur only in minor accessory minerals in the original rock; however, in the weathering residue, these elements are concentrated and occur as separate mineral phases, chiefly birnessite, nsutite, and goethite. Thin veins of pure muscovite and quartz traverse the residua. Rare, pure calcite and maghemite nodules were noted throughout the residual manganese material. The properties of this weathering sequence suggest that the manganese wad deposits were formed in situ as a result of the congruent dissolution of dolomite, leaving a porous, sponge-like structure, highly enriched in Mn and Fe oxides.

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

(1985). Winning—An Ancient Tradition. Journal of Physical Education, Recreation & Dance: Vol. 56, No. 6, pp. 14-15.

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)