Can we build an efficient response to the prescription drug abuse epidemic? Assessing the cost effectiveness of universal prevention in the PROSPER trial

PURPOSE: Prescription drug abuse has reached epidemic proportions. Nonmedical prescription opioid use carries increasingly high costs. Despite the need to cultivate efforts that are both effective and fiscally responsible, the cost-effectiveness of universal evidence-based-preventive-interventions (EBPIs) is rarely evaluated. This study explores the performance of these programs to reduce nonmedical prescription opioid use. METHODS: Sixth graders from twenty-eight rural public school districts in Iowa and Pennsylvania were blocked by size and geographic location and then randomly assigned to experimental or control conditions (2002-2010). Within the intervention communities, prevention teams selected a universal family and school program from a menu of EBPIs. All families were offered a family-based program in the 6(th) grade and received one of three school-based programs in 7(th)-grade. The effectiveness and cost-effectiveness of each school program by itself and with an additional family-based program was assessed using propensity and marginal structural models. RESULTS: This work demonstrates that universal school-based EBPIs can efficiently reduce nonmedical prescription opioid use. Further, findings illustrate that family-based programs may be used to enhance the cost-effectiveness of school-based programs. CONCLUSIONS: Universal EBPIs can effectively and efficiently reduce nonmedical prescription opioid use should be further considered when developing comprehensive responses to this growing national crisis

Developmental mediation of genetic variation in response to the Fast Track Prevention Program

We conducted a developmental analysis of genetic moderation of the effect of the Fast Track intervention on adult externalizing psychopathology. The Fast Track intervention enrolled 891 children at high risk to develop externalizing behavior problems when they were in kindergarten. Half of the enrolled children were randomly assigned to receive 10 years of treatment, with a range of services and resources provided to the children and their families, and the other half to usual care (controls). We previously showed that the effect of the Fast Track intervention on participants\u27 risk of externalizing psychopathology at age 25 years was moderated by a variant in the glucocorticoid receptor gene. Children who carried copies of the A allele of the single nucleotide polymorphism rs10482672 had the highest risk of externalizing psychopathology if they were in the control arm of the trial and the lowest risk of externalizing psychopathology if they were in the treatment arm. In this study, we test a developmental hypothesis about the origins of this for better and for worse Gene × Intervention interaction (G × I): that the observed G × I effect on adult psychopathology is mediated by the proximal impact of intervention on childhood externalizing problems and adolescent substance use and delinquency. We analyzed longitudinal data tracking the 270 European American children in the Fast Track randomized control trial with available genetic information (129 intervention children, 141 control group peers, 69% male) from kindergarten through age 25 years. Results show that the same pattern of for better and for worse susceptibility to intervention observed at the age 25 follow-up was evident already during childhood. At the elementary school follow-ups and at the middle/high school follow-ups, rs10482672 predicted better adjustment among children receiving the Fast Track intervention and worse adjustment among children in the control condition. In turn, these proximal G × I effects early in development mediated the ultimate G × I effect on externalizing psychopathology at age 25 years. We discuss the contribution of these findings to the growing literature on genetic susceptibility to environmental intervention

Developmental mediation of genetic variation in response to the Fast Track Prevention Program

We conducted a developmental analysis of genetic moderation of the effect of the Fast Track intervention on adult externalizing psychopathology. The Fast Track intervention enrolled 891 children at high risk to develop externalizing behavior problems when they were in kindergarten. Half of the enrolled children were randomly assigned to receive 10 years of treatment, with a range of services and resources provided to the children and their families, and the other half to usual care (controls). We previously showed that the effect of the Fast Track intervention on participants\u27 risk of externalizing psychopathology at age 25 years was moderated by a variant in the glucocorticoid receptor gene. Children who carried copies of the A allele of the single nucleotide polymorphism rs10482672 had the highest risk of externalizing psychopathology if they were in the control arm of the trial and the lowest risk of externalizing psychopathology if they were in the treatment arm. In this study, we test a developmental hypothesis about the origins of this for better and for worse Gene × Intervention interaction (G × I): that the observed G × I effect on adult psychopathology is mediated by the proximal impact of intervention on childhood externalizing problems and adolescent substance use and delinquency. We analyzed longitudinal data tracking the 270 European American children in the Fast Track randomized control trial with available genetic information (129 intervention children, 141 control group peers, 69% male) from kindergarten through age 25 years. Results show that the same pattern of for better and for worse susceptibility to intervention observed at the age 25 follow-up was evident already during childhood. At the elementary school follow-ups and at the middle/high school follow-ups, rs10482672 predicted better adjustment among children receiving the Fast Track intervention and worse adjustment among children in the control condition. In turn, these proximal G × I effects early in development mediated the ultimate G × I effect on externalizing psychopathology at age 25 years. We discuss the contribution of these findings to the growing literature on genetic susceptibility to environmental intervention

Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial

Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era

Simons Observatory: Observatory Scheduler and Automated Data Processing

The Simons Observatory (SO) is a next-generation ground-based telescope located in the Atacama Desert in Chile, designed to map the cosmic microwave background (CMB) with unprecedented precision. The observatory consists of three small aperture telescopes (SATs) and one large aperture telescope (LAT), each optimized for distinct but complementary scientific goals. To achieve these goals, optimized scan strategies have been defined for both the SATs and LAT. This paper describes a software system deployed in SO that effectively translates high-level scan strategies into realistic observing scripts executable by the telescope, taking into account realistic observational constraints. The data volume of SO also necessitates a scalable software infrastructure to support its daily data processing needs. This paper also outlines an automated workflow system for managing data packaging and daily data reduction at the site.Comment: 16 pages, 7 figures, 6 tables, to be presented at SPIE Astronomical Telescopes + Instrumentation 202

Lawmakers\u27 Use of Scientific Evidence Can Be Improved

Core to the goal of scientific exploration is the opportunity to guide future decision-making. Yet, elected officials often miss opportunities to use science in their policymaking. This work reports on an experiment with the US Congress-evaluating the effects of a randomized, dual-population (i.e., researchers and congressional offices) outreach model for supporting legislative use of research evidence regarding child and family policy issues. In this experiment, we found that congressional offices randomized to the intervention reported greater value of research for understanding issues than the control group following implementation. More research use was also observed in legislation introduced by the intervention group. Further, we found that researchers randomized to the intervention advanced their own policy knowledge and engagement as well as reported benefits for their research following implementation

The Simons Observatory: Design, integration, and testing of the small aperture telescopes

The Simons Observatory (SO) is a cosmic microwave background (CMB) survey experiment that includes small-aperture telescopes (SATs) observing from an altitude of 5,200 m in the Atacama Desert in Chile. The SO SATs will cover six spectral bands between 27 and 280 GHz to search for primordial B-modes to a sensitivity of $\sigma(r)=0.002$, with quantified systematic errors well below this value. Each SAT is a self-contained cryogenic telescope with a 35$^\circ$ field of view, 42 cm diameter optical aperture, 40 K half-wave plate, 1 K refractive optics, and $12,000$ TES detectors. We describe the nominal design of the SATs and present details about the integration and testing for one operating at 93 and 145 GHz

Lawmakers' use of scientific evidence can be improved.

Core to the goal of scientific exploration is the opportunity to guide future decision-making. Yet, elected officials often miss opportunities to use science in their policymaking. This work reports on an experiment with the US Congress-evaluating the effects of a randomized, dual-population (i.e., researchers and congressional offices) outreach model for supporting legislative use of research evidence regarding child and family policy issues. In this experiment, we found that congressional offices randomized to the intervention reported greater value of research for understanding issues than the control group following implementation. More research use was also observed in legislation introduced by the intervention group. Further, we found that researchers randomized to the intervention advanced their own policy knowledge and engagement as well as reported benefits for their research following implementation

The Atacama Cosmology Telescope: DR6 Gravitational Lensing Map and Cosmological Parameters

We present cosmological constraints from a gravitational lensing mass map covering 9400 sq. deg. reconstructed from CMB measurements made by the Atacama Cosmology Telescope (ACT) from 2017 to 2021. In combination with BAO measurements (from SDSS and 6dF), we obtain the amplitude of matter fluctuations $\sigma_8 = 0.819 \pm 0.015$ at 1.8% precision, $S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.840\pm0.028$ and the Hubble constant $H_0= (68.3 \pm 1.1)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1}$ at 1.6% precision. A joint constraint with CMB lensing measured by the Planck satellite yields even more precise values: $\sigma_8 = 0.812 \pm 0.013$, $S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.831\pm0.023$ and $H_0= (68.1 \pm 1.0)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1}$. These measurements agree well with $\Lambda$CDM-model extrapolations from the CMB anisotropies measured by Planck. To compare these constraints to those from the KiDS, DES, and HSC galaxy surveys, we revisit those data sets with a uniform set of assumptions, and find $S_8$ from all three surveys are lower than that from ACT+Planck lensing by varying levels ranging from 1.7-2.1$\sigma$. These results motivate further measurements and comparison, not just between the CMB anisotropies and galaxy lensing, but also between CMB lensing probing $z\sim 0.5-5$ on mostly-linear scales and galaxy lensing at $z\sim 0.5$ on smaller scales. We combine our CMB lensing measurements with CMB anisotropies to constrain extensions of $\Lambda$CDM, limiting the sum of the neutrino masses to $\sum m_{\nu} < 0.12$ eV (95% c.l.), for example. Our results provide independent confirmation that the universe is spatially flat, conforms with general relativity, and is described remarkably well by the $\Lambda$CDM model, while paving a promising path for neutrino physics with gravitational lensing from upcoming ground-based CMB surveys.Comment: 30 pages, 16 figures, prepared for submission to ApJ. Cosmological likelihood data is here: https://lambda.gsfc.nasa.gov/product/act/actadv_prod_table.html ; likelihood software is here: https://github.com/ACTCollaboration/act_dr6_lenslike . Also see companion papers Qu et al and MacCrann et al. Mass maps will be released when papers are publishe

The Atacama Cosmology Telescope: High-resolution component-separated maps across one-third of the sky

Observations of the millimeter sky contain valuable information on a number of signals, including the blackbody cosmic microwave background (CMB), Galactic emissions, and the Compton-$y$ distortion due to the thermal Sunyaev-Zel'dovich (tSZ) effect. Extracting new insight into cosmological and astrophysical questions often requires combining multi-wavelength observations to spectrally isolate one component. In this work, we present a new arcminute-resolution Compton-$y$ map, which traces out the line-of-sight-integrated electron pressure, as well as maps of the CMB in intensity and E-mode polarization, across a third of the sky (around 13,000 sq.~deg.). We produce these through a joint analysis of data from the Atacama Cosmology Telescope (ACT) Data Release 4 and 6 at frequencies of roughly 93, 148, and 225 GHz, together with data from the \textit{Planck} satellite at frequencies between 30 GHz and 545 GHz. We present detailed verification of an internal linear combination pipeline implemented in a needlet frame that allows us to efficiently suppress Galactic contamination and account for spatial variations in the ACT instrument noise. These maps provide a significant advance, in noise levels and resolution, over the existing \textit{Planck} component-separated maps and will enable a host of science goals including studies of cluster and galaxy astrophysics, inferences of the cosmic velocity field, primordial non-Gaussianity searches, and gravitational lensing reconstruction of the CMB.Comment: The Compton-y map and associated products will be made publicly available upon publication of the paper. The CMB T and E mode maps will be made available when the DR6 maps are made publi