Avi Feller

Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture.

We have cultured Plasmodium falciparum directly from the blood of infected individuals to examine patterns of mature-stage gene expression in patient isolates. Analysis of the transcriptome of P. falciparum is complicated by the highly periodic nature of gene expression because small variations in the stage of parasite development between samples can lead to an apparent difference in gene expression values. To address this issue, we have developed statistical likelihood-based methods to estimate cell cycle progression and commitment to asexual or sexual development lineages in our samples based on microscopy and gene expression patterns. In cases subsequently matched for temporal development, we find that transcriptional patterns in ex vivo culture display little variation across patients with diverse clinical profiles and closely resemble transcriptional profiles that occur in vitro. These statistical methods, available to the research community, assist in the design and interpretation of P. falciparum expression profiling experiments where it is difficult to separate true differential expression from cell-cycle dependent expression. We reanalyze an existing dataset of in vivo patient expression profiles and conclude that previously observed discrete variation is consistent with the commitment of a varying proportion of the parasite population to the sexual development lineage.

Algorithmic Decision Making and the Cost of Fairness

Algorithms are now regularly used to decide whether defendants awaiting trial are too dangerous to be released back into the community. In some cases, black defendants are substantially more likely than white defendants to be incorrectly classified as high risk. To mitigate such disparities, several techniques have recently been proposed to achieve algorithmic fairness. Here we reformulate algorithmic fairness as constrained optimization: the objective is to maximize public safety while satisfying formal fairness constraints designed to reduce racial disparities. We show that for several past definitions of fairness, the optimal algorithms that result require detaining defendants above race-specific risk thresholds. We further show that the optimal unconstrained algorithm requires applying a single, uniform threshold to all defendants. The unconstrained algorithm thus maximizes public safety while also satisfying one important understanding of equality: that all individuals are held to the same standard, irrespective of race. Because the optimal constrained and unconstrained algorithms generally differ, there is tension between improving public safety and satisfying prevailing notions of algorithmic fairness. By examining data from Broward County, Florida, we show that this trade-off can be large in practice. We focus on algorithms for pretrial release decisions, but the principles we discuss apply to other domains, and also to human decision makers carrying out structured decision rules.

Compared to what? Variation in the impacts of early childhood education by alternative care type

Early childhood education research often compares a group of children who receive the intervention of interest to a group of children who receive care in a range of different care settings. In this paper, we estimate differential impacts of an early childhood intervention by alternative care setting, using data from the Head Start Impact Study, a large-scale randomized evaluation. To do so, we utilize a Bayesian principal stratification framework to estimate separate impacts for two types of Compliers: those children who would otherwise be in other center-based care when assigned to control and those who would otherwise be in home-based care. We find strong, positive short-term effects of Head Start on receptive vocabulary for those Compliers who would otherwise be in home-based care. By contrast, we find no meaningful impact of Head Start on vocabulary for those Compliers who would otherwise be in other center-based care. Our findings suggest that alternative care type is a potentially important source of variation in early childhood education interventions.

Genome-wide profiling of chromosome interactions in Plasmodium falciparum characterizes nuclear architecture and reconfigurations associated with antigenic variation.

Spatial relationships within the eukaryotic nucleus are essential for proper nuclear function. In Plasmodium falciparum, the repositioning of chromosomes has been implicated in the regulation of the expression of genes responsible for antigenic variation, and the formation of a single, peri‐nuclear nucleolus results in the clustering of rDNA. Nevertheless, the precise spatial relationships between chromosomes remain poorly understood, because, until recently, techniques with sufficient resolution have been lacking. Here we have used chromosome conformation capture and second‐generation sequencing to study changes in chromosome folding and spatial positioning that occur during switches in var gene expression. We have generated maps of chromosomal spatial affinities within the P. falciparum nucleus at 25 Kb resolution, revealing a structured nucleolus, an absence of chromosome territories, and confirming previously identified clustering of heterochromatin foci. We show that switches in var gene expression do not appear to involve interaction with a distant enhancer, but do result in local changes at the active locus. These maps reveal the folding properties of malaria chromosomes, validate known physical associations, and characterize the global landscape of spatial interactions. Collectively, our data provide critical information for a better understanding of gene expression regulation and antigenic variation in malaria parasites.

Discouraged by Peer Excellence Exposure to Exemplary Peer Performance Causes Quitting

People are exposed to exemplary peer performances often (and sometimes by design in interventions). In two studies, we showed that exposure to exemplary peer performances can undermine motivation and success by causing people to perceive that they cannot attain their peers’ high levels of performance. It also causes de-identification with the relevant domain. We examined such discouragement by peer excellence by exploiting the incidental exposure to peers’ abilities that occurs when students are asked to assess each other’s work. Study 1 was a natural experiment in a massive open online course that employed peer assessment (N = 5,740). Exposure to exemplary peer performances caused a large proportion of students to quit the course. Study 2 explored underlying psychological mechanisms in an online replication (N = 361). Discouragement by peer excellence has theoretical implications for work on social judgment, social comparison, and reference bias and has practical implications for interventions that induce social comparisons.

Principal Stratification A Tool for Understanding Variation in Program Effects Across Endogenous Subgroups

Increasingly, researchers are interested in questions regarding treatment-effect variation across partially or fully latent subgroups defined not by pretreatment characteristics but by postrandomization actions. One promising approach to address such questions is principal stratification. Under this framework, a researcher defines endogenous subgroups, or principal strata, based on post-randomization behaviors under both the observed and the counterfactual experimental conditions. These principal strata give structure to such research questions and provide a framework for determining estimation strategies to obtain desired effect estimates. This article provides a nontechnical primer to principal stratification. We review selected applications to highlight the breadth of substantive questions and methodological issues that this method can inform. We then discuss its relationship to instrumental variables analysis to address binary noncompliance in an experimental context and highlight how the framework can be generalized to handle more complex posttreatment patterns. We emphasize the counterfactual logic fundamental to principal stratification and the key assumptions that render analytic challenges more tractable. We briefly discuss technical aspects of estimation procedures, providing a short guide for interested readers.

The Millennium Villages Project: a retrospective, observational, endline evaluation

BACKGROUND The Millennium Villages Project (MVP) was a 10 year, multisector, rural development project, initiated in 2005, operating across ten sites in ten sub-Saharan African countries to achieve the Millennium Development Goals (MDGs). In this study, we aimed to estimate the projects impact, target attainment, and on-site spending. METHODS In this endline evaluation of the MVP, we retrospectively selected comparison villages that best matched the project villages on possible confounding variables. Cross-sectional survey data on 40 outcomes of interest were collected from both the project and the comparison villages in 2015. Using these data, as well as on-site spending data collected during the project, we estimated project impacts as differences in outcomes between the project and comparison villages; target attainment as differences between project outcomes and prespecified targets; and on-site spending as expenditures reported by communities, donors, governments, and the project. Spending data were not collected in the comparison villages. FINDINGS Averaged across the ten project sites, we found that impact estimates for 30 of 40 outcomes were significant (95% uncertainty intervals [UIs] for these outcomes excluded zero) and favoured the project villages. In particular, substantial effects were seen in agriculture and health, in which some outcomes were roughly one SD better in the project villages than in the comparison villages. The project was estimated to have no significant impact on the consumption-based measures of poverty, but a significant favourable impact on an index of asset ownership. Impacts on nutrition and education outcomes were often inconclusive (95% UIs included zero). Averaging across outcomes within categories, the project had significant favourable impacts on agriculture, nutrition, education, child health, maternal health, HIV and malaria, and water and sanitation. A third of the targets were met in the project sites. Total on-site spending decreased from US

Red State/Blue State Divisions in the 2012 Presidential Election

132 per person in the first half of the project (of which

Decomposing Treatment Effect Variation

66 was from the MVP) to

Analyzing two-stage experiments in the presence of interference*

109 per person in the second half of the project (of which