An evaluation of the National Institutes of Health Early Stage Investigator policy: Using existing data to evaluate federal policy.

To assist new scientists in the transition to independent research careers, the National Institutes of Health (NIH) implemented an Early Stage Investigator (ESI) policy beginning with applications submitted in 2009. During the review process, the ESI designation segregates applications submitted by investigators who are within 10 years of completing their terminal degree or medical residency from applications submitted by more experienced investigators. Institutes/centers can then give special consideration to ESI applications when making funding decisions. One goal of this policy is to increase the probability of newly emergent investigators receiving research support. Using optimal matching to generate comparable groups pre- and post-policy implementation, generalized linear models were used to evaluate the ESI policy. Due to a lack of control group, existing data from 2004 to 2008 were leveraged to infer causality of the ESI policy effects on the probability of funding applications from 2011 to 2015. This article addresses the statistical necessities of public policy evaluation, finding administrative data can serve as a control group when proper steps are taken to match the samples. Not only did the ESI policy stabilize the proportion of NIH funded newly emergent investigators but also, in the absence of the ESI policy, 54% of newly emergent investigators would not have received funding. This manuscript is important to Research Evaluation as a demonstration of ways in which existing data can be modeled to evaluate new policy, in the absence of a control group, forming a quasi-experimental design to infer causality when evaluating federal policy.

Regulation of Aedes aegypti population dynamics in field systems: quantifying direct and delayed density dependence.

Transgenic strains of Aedes aegypti have been engineered to help control transmission of dengue virus. Although resources have been invested in developing the strains, we lack data on the ecology of mosquitoes that could impact the success of this approach. Although studies of intra-specific competition have been conducted using Ae. aegypti larvae, none of these studies examine mixed age cohorts at densities that occur in the field, with natural nutrient levels. Experiments were conducted in Mexico to determine the impact of direct and delayed density dependence on Ae. aegypti populations. Natural water, food, and larval densities were used to estimate the impacts of density dependence on larval survival, development, and adult body size. Direct and delayed density-dependent factors had a significant impact on larval survival, larval development, and adult body size. These results indicate that control methods attempting to reduce mosquito populations may be counteracted by density-dependent population regulation.

Field cage studies and progressive evaluation of genetically-engineered mosquitoes.

BACKGROUND: A genetically-engineered strain of the dengue mosquito vector Aedes aegypti, designated OX3604C, was evaluated in large outdoor cage trials for its potential to improve dengue prevention efforts by inducing population suppression. OX3604C is engineered with a repressible genetic construct that causes a female-specific flightless phenotype. Wild-type females that mate with homozygous OX3604C males will not produce reproductive female offspring. Weekly introductions of OX3604C males eliminated all three targeted Ae. aegypti populations after 10-20 weeks in a previous laboratory cage experiment. As part of the phased, progressive evaluation of this technology, we carried out an assessment in large outdoor field enclosures in dengue endemic southern Mexico. METHODOLOGY/PRINCIPAL FINDINGS: OX3604C males were introduced weekly into field cages containing stable target populations, initially at 10:1 ratios. Statistically significant target population decreases were detected in 4 of 5 treatment cages after 17 weeks, but none of the treatment populations were eliminated. Mating competitiveness experiments, carried out to explore the discrepancy between lab and field cage results revealed a maximum mating disadvantage of up 59.1% for OX3604C males, which accounted for a significant part of the 97% fitness cost predicted by a mathematical model to be necessary to produce the field cage results. CONCLUSIONS/SIGNIFICANCE: Our results indicate that OX3604C may not be effective in large-scale releases. A strain with the same transgene that is not encumbered by a large mating disadvantage, however, could have improved prospects for dengue prevention. Insights from large outdoor cage experiments may provide an important part of the progressive, stepwise evaluation of genetically-engineered mosquitoes.

An experimental field study of delayed density dependence in natural populations of Aedes albopictus.

Aedes albopictus, a species known to transmit dengue and chikungunya viruses, is primarily a container-inhabiting mosquito. The potential for pathogen transmission by Ae. albopictus has increased our need to understand its ecology and population dynamics. Two parameters that we know little about are the impact of direct density-dependence and delayed density-dependence in the larval stage. The present study uses a manipulative experimental design, under field conditions, to understand the impact of delayed density dependence in a natural population of Ae. albopictus in Raleigh, North Carolina. Twenty liter buckets, divided in half prior to experimentation, placed in the field accumulated rainwater and detritus, providing oviposition and larval production sites for natural populations of Ae. albopictus. Two treatments, a larvae present and larvae absent treatment, were produced in each bucket. After five weeks all larvae were removed from both treatments and the buckets were covered with fine mesh cloth. Equal numbers of first instars were added to both treatments in every bucket. Pupae were collected daily and adults were frozen as they emerged. We found a significant impact of delayed density-dependence on larval survival, development time and adult body size in containers with high larval densities. Our results indicate that delayed density-dependence will have negative impacts on the mosquito population when larval densities are high enough to deplete accessible nutrients faster than the rate of natural food accumulation.