Polling places, pharmacies, and public health: Vote & Vax 2012.

US national elections, which draw sizable numbers of older voters, take place during flu-shot season and represent an untapped opportunity for large-scale delivery of vaccinations. In 2012, Vote & Vax deployed a total of 1585 clinics in 48 states; Washington, DC; Guam; Puerto Rico; and the US Virgin Islands. Approximately 934 clinics were located in pharmacies, and 651 were near polling places. Polling place clinics delivered significantly more vaccines than did pharmacies (5710 vs 3669). The delivery of vaccines was estimated at 9379, and approximately 45% of the recipients identified their race/ethnicity as African American or Hispanic. More than half of the White Vote & Vax recipients and more than two thirds of the non-White recipients were not regular flu shot recipients.

A randomized controlled trial evaluating the effects of nurse-led triage of 911 calls.

To better connect non-emergent 911 callers to appropriate care, Washington, DC, routed low-acuity callers to nurses. Nurses could provide non-emergent transportation to a health centre, recommend self-care or return callers to the traditional 911 system. Over about one year, 6,053 callers were randomized (1:1) to receive a business-as-usual response (ncontrol = 3,023) or further triage (ntreatment = 3,030). We report on seven of nine outcomes, which were pre-registered ( https://osf.io/xderw ). The proportion of calls resulting in an ambulance dispatch dropped from 97% to 56% (ß = -1.216 (-1.324, -1.108), P < 0.001), and those resulting in an ambulance transport dropped from 73% to 45% (ß = -3.376 (-3.615, -3.137), P < 0.001). Among those callers who were Medicaid beneficiaries, within 24 hours, the proportion of calls resulting in an emergency department visit for issues classified as non-emergent or primary care physician (PCP) treatable dropped from 29.5% to 25.1% (ß = -0.230 (-0.391, -0.069), P < 0.001), and the proportion resulting in the caller visiting a PCP rose from 2.5% to 8.2% (ß = 1.252 (0.889, 1.615), P < 0.001). Over the longer time span of six months, we failed to detect evidence of impacts on emergency department visits, PCP visits or Medicaid expenditures. From a safety perspective, 13 callers randomized to treatment were eventually diagnosed with a time-sensitive illness, all of whom were quickly triaged to an ambulance response. These short-term effects suggest that nurse-led triage of non-emergent calls can safely connect callers to more appropriate, timely care.

Leukemia/lymphoma-related factor regulates oligodendrocyte lineage cell differentiation in developing white matter.

Leukemia/lymphoma-related factor (LRF) is a zinc-finger transcription factor that regulates differentiation and oncogenesis in multiple tissues and cell lineages. The potential role for LRF in cells of the CNS has not been examined to date. This study shows prominent nuclear expression of LRF in diverse neuronal populations and in oligodendrocytes. We focused on examining the function of LRF during the transition from oligodendrocyte progenitor (OP) to mature oligodendrocyte that is associated with myelination in the postnatal spinal cord. During spinal cord myelination, LRF is expressed in only a minority of OP cells whereas most mature oligodendrocytes exhibited nuclear LRF immunoreactivity. Mice with floxed alleles of the Zbtb7a gene, which encodes for LRF protein, were used for in vivo analysis of LRF function. Lentiviral driven Cre recombinase inactivation of LRF at postnatal day 7 reduced the proportion of OP cells that differentiated into mature oligodendrocytes by postnatal day 28. Astrocyte populations were not altered by LRF deletion in the same tissues. These results indicate that LRF deletion reduces differentiation within the oligodendrocyte lineage and does not alter OP lineage choice. In vitro analysis confirmed a specific effect of LRF on OP differentiation. In neonatal OP cultures, RNA interference targeting LRF inhibited OP differentiation while LRF transduction was sufficient to induce differentiation into oligodendrocytes. These results support a critical role for LRF in transcriptional control of differentiation in oligodendrocyte lineage cells during developmental myelination in the CNS.

Who loses in direct democracy?

We examine the success of California's black, Latino, and Asian voters in ballot proposition elections, showing that minority voters lose more often than whites across all ballot propositions, and that this disadvantage is not limited to a small subset of racially-targeted propositions. Minority voters are 2-5 percentage points less likely than otherwise-similar white voters to be on the winning side of ballot propositions. These differences persist after excluding racially-targeted propositions because minority voters are more likely to lose on several issues including elections, the environment, health, housing, taxes, and transportation. We demonstrate that race is more important than class in describing which voters lose.

Public policy for the poor? A randomised assessment of the Mexican universal health insurance programme.

BACKGROUND: We assessed aspects of Seguro Popular, a programme aimed to deliver health insurance, regular and preventive medical care, medicines, and health facilities to 50 million uninsured Mexicans. METHODS: We randomly assigned treatment within 74 matched pairs of health clusters-ie, health facility catchment areas-representing 118 569 households in seven Mexican states, and measured outcomes in a 2005 baseline survey (August, 2005, to September, 2005) and follow-up survey 10 months later (July, 2006, to August, 2006) in 50 pairs (n=32 515). The treatment consisted of encouragement to enrol in a health-insurance programme and upgraded medical facilities. Participant states also received funds to improve health facilities and to provide medications for services in treated clusters. We estimated intention to treat and complier average causal effects non-parametrically. FINDINGS: Intention-to-treat estimates indicated a 23% reduction from baseline in catastrophic expenditures (1.9% points; 95% CI 0.14-3.66). The effect in poor households was 3.0% points (0.46-5.54) and in experimental compliers was 6.5% points (1.65-11.28), 30% and 59% reductions, respectively. The intention-to-treat effect on health spending in poor households was 426 pesos (39-812), and the complier average causal effect was 915 pesos (147-1684). Contrary to expectations and previous observational research, we found no effects on medication spending, health outcomes, or utilisation. INTERPRETATION: Programme resources reached the poor. However, the programme did not show some other effects, possibly due to the short duration of treatment (10 months). Although Seguro Popular seems to be successful at this early stage, further experiments and follow-up studies, with longer assessment periods, are needed to ascertain the long-term effects of the programme.

Improved Use of Human Milk, Growth, and Central Line Utilization With Standard Feeding Roadmap in an Academic NICU.

BACKGROUND: Before the initiation of a standardized feeding roadmap in our regional, level IV academic neonatal intensive care unit, utilization of central lines was high, and initiation of enteral feeds delayed in the very low-birth-weight population (<1500 g). Given our review of the literature, it appeared that the standardization of feeding advancement would likely result in improved performance in both issues. METHODS: This was a retrospective cohort comparison of very low-birth-weight patients before initiation of any feeding roadmap with a second cohort following completion of the final roadmap. Infants were examined retrospectively in 2 historical cohorts: Phase 1, infants fed before roadmap development and rollout, October 1, 2012-March 31, 2013; and Phase 2, following promulgation of the final feeding roadmap, January 1, 2017-June 30, 2017. RESULTS: During Phase 2, we observed a significant reduction in median (interquartile range) days to first feed (3 [1] vs 1 [1] [P < 0.0001]) and utilization of a second central line (35% vs 12% [P < 0.01]). Weight gain was significantly improved from before roadmap implementation to final, mean (SD) (g/d, 21 [5] vs 24 [4]; [P < .0001]). Percentage of first enteral feedings that were human milk also increased significantly from 71% to 91% (P = 0.0007). CONCLUSION: Implementation of a standardized feeding roadmap was associated with a reduction in days to first enteral feeds, an increase in the primary use of human milk for initiation of enteral feeds, and a decrease in the utilization of central lines while improving weight gain in very low-birth-weight infants.

Blocking for Sequential Political Experiments.

In typical political experiments, researchers randomize a set of households, precincts, or individuals to treatments all at once, and characteristics of all units are known at the time of randomization. However, in many other experiments, subjects "trickle in" to be randomized to treatment conditions, usually via complete randomization. To take advantage of the rich background data that researchers often have (but underutilize) in these experiments, we develop methods that use continuous covariates to assign treatments sequentially. We build on biased coin and minimization procedures for discrete covariates and demonstrate that our methods outperform complete randomization, producing better covariate balance in simulated data. We then describe how we selected and deployed a sequential blocking method in a clinical trial and demonstrate the advantages of our having done so. Further, we show how that method would have performed in two larger sequential political trials. Finally, we compare causal effect estimates from differences in means, augmented inverse propensity weighted estimators, and randomization test inversion.

Human cancer cells commonly acquire DNA damage during mitotic arrest.

The mitotic checkpoint is a mechanism that arrests the progression to anaphase until all chromosomes have achieved proper attachment to mitotic spindles. In cancer cells, satisfaction of this checkpoint is frequently delayed or prevented by various defects, some of which have been causally implicated in tumorigenesis. At the same time, deliberate induction of mitotic arrest has proved clinically useful, as antimitotic drugs that interfere with proper chromosome-spindle interactions are effective anticancer agents. However, how mitotic arrest contributes to tumorigenesis or antimitotic drug toxicity is not well defined. Here, we report that mitotic chromosomes can acquire DNA breaks during both pharmacologic and genetic induction of mitotic arrest in human cancer cells. These breaks activate a DNA damage response, occur independently of cell death, and subsequently manifest as karyotype alterations. Such breaks can also occur spontaneously, particularly in cancer cells containing mitotic spindle abnormalities. Moreover, we observed evidence of some breakage in primary human cells. Our findings thus describe a novel source of DNA damage in human cells. They also suggest that mitotic arrest may promote tumorigenesis and antimitotic toxicity by provoking DNA damage.

A "politically robust" experimental design for public policy evaluation, with application to the Mexican universal health insurance program.

We develop an approach to conducting large-scale randomized public policy experiments intended to be more robust to the political interventions that have ruined some or all parts of many similar previous efforts. Our proposed design is insulated from selection bias in some circumstances even if we lose observations; our inferences can still be unbiased even if politics disrupts any two of the three steps in our analytical procedures; and other empirical checks are available to validate the overall design. We illustrate with a design and empirical validation of an evaluation of the Mexican Seguro Popular de Salud (Universal Health Insurance)program we are conducting. Seguro Popular, which is intended to grow to provide medical care, drugs, preventative services, and financial health protection to the 50 million Mexicans without health insurance, is one of the largest health reforms of any country in the last two decades. The evaluation is also large scale, constituting one of the largest policy experiments to date and what may be the largest randomized health policy experiment ever.