Mammalian cell types exhibit specialized metabolism, and there is ample evidence that various co-existing cell types engage in metabolic cooperation. Moreover, even cultures of a single cell type may contain cells in distinct metabolic states, such as resting or cycling cells. Methods for measuring metabolic activities of such subpopulations are valuable tools for understanding cellular metabolism. Complex cell populations are most commonly separated using a cell sorter, and subpopulations isolated by this method can be analyzed by metabolomics methods. However, a problem with this approach is that the cell sorting procedure subjects cells to stresses that may distort their metabolism. To overcome these issues, we reasoned that the mass isotopomer distributions (MIDs) of metabolites from cells cultured with stable isotope-labeled nutrients are likely to be more stable than absolute metabolite concentrations, because MIDs are formed over longer time scales and should be less affected by short-term exposure to cell sorting conditions. Here, we describe a method based on this principle, combining cell sorting with liquid chromatography-high resolution mass spectrometry (LC-HRMS). The procedure involves analyzing three types of samples: (1) metabolite extracts obtained directly from the complex population; (2) extracts of "mock sorted" cells passed through the cell sorter instrument without gating any specific population; and (3) extracts of the actual sorted populations. The mock sorted cells are compared against direct extraction to verify that MIDs are indeed not altered by the cell sorting procedure itself, prior to analyzing the actual sorted populations. We show example results from HeLa cells sorted according to cell cycle phase, revealing changes in nucleotide metabolism.
We present the results of three large-scale randomized controlled trials (RCTs) carried out in Chicago, testing interventions to reduce crime and dropout by changing the decision making of economically disadvantaged youth. We study a program called Becoming a Man (BAM), developed by the nonprofit Youth Guidance, in two RCTs implemented in 2009-2010 and 2013-2015. In the two studies participation in the program reduced total arrests during the intervention period by 28-35%, reduced violent-crime arrests by 45-50%, improved school engagement, and in the first study where we have follow-up data, increased graduation rates by 12-19%. The third RCT tested a program with partially overlapping components carried out in the Cook County Juvenile Temporary Detention Center (JTDC), which reduced readmission rates to the facility by 21%. These large behavioral responses combined with modest program costs imply benefit-cost ratios for these interventions from 5-to-1 up to 30-to-1 or more. Our data on mechanisms are not ideal, but we find no positive evidence that these effects are due to changes in emotional intelligence or social skills, self-control or "grit," or a generic mentoring effect. We find suggestive support for the hypothesis that the programs work by helping youth slow down and reflect on whether their automatic thoughts and behaviors are well suited to the situation they are in, or whether the situation could be construed differently. JEL Codes: C91, C93, D03, D1, I24, I3, I32, K42.
We use a randomized controlled trial to study the response of poor households in rural Kenya to unconditional cash transfers from the NGO GiveDirectly. The transfers differ from other programs in that they are explicitly unconditional, large, and concentrated in time. We randomized at both the village and household levels; furthermore, within the treatment group, we randomized recipient gender (wife versus husband), transfer timing (lump-sum transfer versus monthly installments), and transfer magnitude (US$404 PPP versus US$1,525 PPP). We find a strong consumption response to transfers, with an increase in household monthly consumption from $158 PPP to $193 PPP nine months after the transfer began. Transfer recipients experience large increases in psychological well-being. We find no overall effect on levels of the stress hormone cortisol, although there are differences across some subgroups. Monthly transfers are more likely than lump-sum transfers to improve food security, whereas lump-sum transfers are more likely to be spent on durables, suggesting that households face savings and credit constraints. Together, these results suggest that unconditional cash transfers have significant impacts on economic outcomes and psychological well-being.

