Antimicrobials are used primarily to treat infectious disease, but they have other effects. Here, we assess anthropometry measurements in children 6-60 months in 24 communities randomized to one or ...two mass azithromycin distributions over a 1-year period in Niger. We compared the prevalence of wasting, low mid-upper arm circumference, stunting, and underweight in communities in the two treatment arms. We were unable to prove that there was a difference in the prevalence of wasting in the 12 communities that received one mass azithromycin distribution versus the 12 communities that received two mass azithromycin distributions (odds ratio = 0.75, 95% confidence interval = 0.46-1.23). Likewise, we were unable to detect a difference in the two treatment arms for low mid-upper arm circumference, stunting, and underweight. There may not be an association between antibiotic use and improved growth in humans, or this trial was not powerful enough to detect an association if it exists.
Repeated mass azithromycin distributions are effective in controlling the ocular strains of chlamydia that cause trachoma. However, it is unclear when treatments can be discontinued. Investigators ...have proposed graduating communities when the prevalence of infection identified in children decreases below a threshold. While this can be tested empirically, results will not be available for years. Here we use a mathematical model to predict results with different graduation strategies in three African countries.
A stochastic model of trachoma transmission was constructed, using the parameters with the maximum likelihood of obtaining results observed from studies in Tanzania (with 16% infection in children pre-treatment), The Gambia (9%), and Ethiopia (64%). The expected prevalence of infection at 3 years was obtained, given different thresholds for graduation and varying the characteristics of the diagnostic test.
The model projects that three annual treatments at 80% coverage would reduce the mean prevalence of infection to 0.03% in Tanzanian, 2.4% in Gambian, and 12.9% in the Ethiopian communities. If communities graduate when the prevalence of infection falls below 5%, then the mean prevalence at 3 years with the new strategy would be 0.3%, 3.9%, and 14.4%, respectively. Graduations reduced antibiotic usage by 63% in Tanzania, 56% in The Gambia, and 11% in Ethiopia.
Models suggest that graduating communities from a program when the infection is reduced to 5% is a reasonable strategy and could reduce the amount of antibiotic distributed in some areas by more than 2-fold.
The scholarly turn to the unilateral presidency has expanded our understanding of the presidency and executive power, but, to date, this body of work has focused on presidents since the New Deal. ...This is somewhat surprising, given that many of the most well-known unilateral orders were issued before 1900. Rather than being isolated events, they are part of a longer list of unilateral presidential orders among early presidents that, as a group, have received little scholarly attention. This article seeks, first, to introduce "settle down" proclamations (which are issued as warnings to the public) issued by presidents before Theodore Roosevelt as a way to further understand the development of executive power in the early presidency. Second, it uses these proclamations to test whether the findings of the unilateral presidency scholarship hold with respect to unilateral power before the twentieth century. The article concludes by comparing unilateral power to prerogative power and proposing a path for future research.
Mass azithromycin distributions may decrease childhood mortality, although the causal pathway is unclear. The potential for antibiotics to function as growth promoters may explain some of the ...mortality benefit.
To investigate whether biannual mass azithromycin distributions are associated with increased childhood growth.
This cluster-randomized trial was performed from December 2014 until March 2020 among 30 rural communities in Boboye and Loga departments in Niger, Africa, with populations from 200 to 2000 individuals. Communities were randomized in a 1:1 ratio to biannual mass distributions of azithromycin or placebo for children ages 1 to 59 months. Participants, field-workers, and study personnel were masked to treatment allocation. Height and weight changes from baseline to follow-up at 4 years were compared between groups. Data were analyzed from June through November 2021.
Participants received azithromycin at 20 mg/kg using height-based approximation or by weight for children unable to stand every 6 months at the participants' households. Placebo contained the vehicle of the azithromycin suspension.
Longitudinal anthropometric assessments were performed on a random sample of children before the first treatment and then annually for 5 years. Height and weight were the prespecified primary outcomes.
Among 3936 children enrolled from 30 communities, baseline characteristics were similar between 1299 children in the azithromycin group and 2637 children in the placebo group (mean 48.2% 95% CI, 45.5% to 50.8% girls vs 48.0% 95% CI, 45.7% to 50.3% girls; mean age, 30.8 months 95% CI, 29.5 to 32.0 months vs 30.6 months 95% CI, 29.2 to 31.6 months). Baseline anthropometric assessments were performed among 2230 children, including 985 children in the azithromycin group and 1245 children in the placebo group, of whom follow-up measurements were available for 789 children (80.1%) and 1063 children (85.4%), respectively. At the prespecified 4-year follow-up visit, children in the azithromycin group gained a mean 6.7 cm (95% CI, 6.5 to 6.8 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year and children in the placebo group gained a mean 6.6 cm (95% CI, 6.4 to 6.7 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year. Height at 4 years was not statistically significantly different between groups when adjusted for baseline height (0.08 cm 95% CI, -0.12 to 0.28 cm greater in the azithromycin group; P = .45), and neither was weight when adjusted for height and baseline weight (0.02 kg 95% CI, -0.10 to 0.06 kg less in the azithromycin group; P = .64). However, among children in the shortest quartile of baseline height, azithromycin was associated with a 0.4 cm (95% CI, 0.1 to 0.7 cm) increase in height compared with placebo.
This study did not find evidence of an association between mass azithromycin distributions and childhood growth, although subgroup analysis suggested some benefit for the shortest children. These findings suggest that the mortality benefit of mass azithromycin distributions is unlikely to be due solely to growth promotion.
ClinicalTrials.gov Identifier: NCT02048007.
Decisions affecting wildlife management and conservation policy of imperiled species are often aided by population models. Reliable population models require accurate estimates of vital rates and an ...understanding of how vital rates vary geographically. The eastern massasauga (Sistrurus catenatus catenatus) is a rattlesnake species found in the Great Lakes region of North America. Populations of the eastern massasauga are fragmented and only a few areas harbor multiple, sizable populations. Eastern massasauga research has typically focused on single populations or local metapopulations but results suggest that demographic parameters vary geographically. We used 21 radiotelemetry datasets comprising 499 telemetered snakes from 16 distinct locations throughout the range of the eastern massasauga to characterize geographic patterns of adult survival using the known-fate model in Program MARK. Annual adult survival ranged from 0.35 to 0.95 (mean = 0.67) and increased along a southwest to northeast geographic axis. Further analysis of 6 datasets indicated no consistent difference in survival between males and females. Our results provide a better understanding of the relationship between survivorship and geography for the eastern massasauga and suggest that such variation should be incorporated into population models as well as local and regional management plans.
Importance Because transmission of ocular strains ofChlamydia trachomatisis greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and ...result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources. Objective To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease. Design, Setting, and Participants In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022. Interventions Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months. Main Outcomes and Measures Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation–follicular and trachomatous inflammation–intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies toC trachomatisantigens. Results At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean SD proportions of boys, 51.8% 4.7% vs 52.0% 4.2%; mean SD age, 30.8 2.8 vs 30.6 2.6 months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation–follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation–follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 95% CI, 0.01-1.20; permutationP = .07). Conclusions and Relevance The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger. Trial Registration ClinicalTrials.gov Identifier:NCT02048007
According to Tillman, when Hamilton wrote "the consent of the Senate would be necessary to displace as well as to appoint,"12 he was not addressing who had the power to remove executive branch ...officers, but who had the authority to replace them. ... even if Hamilton supported unilateral presidential removals in 1789 (the traditional view, and a point I contest actively in my 2008 article), it would not establish that Hamilton had changed his mind.13 Tillman's new view and my own are both scholarly outliers.
By revisiting Thomas Jefferson's understanding of executive power this book offers a new understanding of the origins of presidential power. Before Jefferson was elected president, he arrived at a ...way to resolve the tension between constitutionalism and executive power. Because his solution would preserve a strict interpretation of the Constitution as well as transform the precedents left by his Federalist predecessors, it provided an alternative to Alexander Hamilton's understanding of executive power. In fact, a more thorough account of Jefferson's political career suggests that Jefferson envisioned an executive that was powerful, or 'energetic', because it would be more explicitly attached to the majority will. Jefferson's Revolution of 1800, often portrayed as a reversal of the strong presidency, was itself premised on energy in the executive and was part of Jefferson's project to enable the Constitution to survive and even flourish in a world governed by necessity.
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