9 research outputs found
A Conditional Randomization Test to Account for Covariate Imbalance in Randomized Experiments
We consider the conditional randomization test as a way to account for covariate imbalance in randomized experiments. The test accounts for covariate imbalance by comparing the observed test statistic to the null distribution of the test statistic conditional on the observed covariate imbalance. We prove that the conditional randomization test has the correct significance level and introduce original notation to describe covariate balance more formally. Through simulation, we verify that conditional randomization tests behave like more traditional forms of covariate adjustmet but have the added benefit of having the correct conditional significance level. Finally, we apply the approach to a randomized product marketing experiment where covariate information was collected after randomization
The progestin receptor interactome in the female mouse hypothalamus: Interactions with synaptic proteins are isoform specific and ligand dependent
Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase–tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot. Synaptic proteins, including synapsin-I and synapsin-II, interacted with agonist-bound PR isoforms, suggesting that both isoforms function in synaptic plasticity. In further support, synaptogyrin-III and synapsin-III associated with PR-A and PR-B, respectively. PR also interacted with kinases, including c-Src, mTOR, and MAPK1, confirming phosphorylation as an integral process in rapid effects of PR in the brain. Consistent with a role in transcriptional regulation, PR associated with transcription factors and coactivators in a ligand-specific and isoform-dependent manner. Interestingly, both PR isoforms associated with a key regulator of energy homeostasis, FoxO1, suggesting a novel role for PR in energy metabolism. Because many identified proteins in this PR interactome are synaptic proteins, we tested the hypothesis that progestins function in synaptic plasticity. Indeed, progesterone enhanced synaptic density, by increasing synapsin-I–positive synapses, in rat primary cortical neuronal cultures. This novel combination of RPPA and mass spectrometry allowed identification of PR action in synaptic remodeling and energy homeostasis and reveals unique roles for progestins in brain function and disease
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The Limits of Unbundled Legal Assistance: A Randomized Study in a Massachusetts District Court and Prospects for the Future
We persuaded entities conducting two legal aid programs designed to provide evidence regarding a civil right to counsel to allow us to randomize which potential clients would receive offers of traditional attorney-client relationships from legal aid provider staff attorneys and which would receive only limited (“unbundled”) assistance. In both pilot programs, potential clients were occupants facing eviction from their housing units, and in neither pilot program did the legal aid provider have capacity sufficient to offer full representation to all occupants who sought it. In this Article, we report the results of one of the two randomized trials, which we label the “District Court Study” after the type of court in which it took place. In this District Court Study, most occupants who became part of the study population received limited assistance in how-to sessions, which included instruction on the summary eviction process as well as help in filling out answer and discovery request forms. After receiving this “unbundled” assistance, members of a randomly selected treated group were offered a traditional attorney-client relationship from a legal aid provider staff attorney; members of the remaining randomly selected control group received no such offer. We compared outcomes for the treated group versus the control group on a variety of dimensions, focusing primarily on possession of the unit, financial consequences of the litigation, and measures of court burden.
At least for the clientele involved in this District Court Study – a clientele recruited and chosen by the legal aid provider’s proactive, timely, specific, and selective outreach and intake system – an offer of full representation mattered. Approximately two-thirds of occupants in the treated group, versus about one-third of occupants in the control group, retained possession of their units at the end of litigation. Using a conservative proxy for financial consequences, and based on a subset of cases in which financial issues were at the forefront, treated-group occupants received payments or rent waivers worth on average a net of 9.4 months of rent per case, versus 1.9 months of rent per case in the control group. Both results were statistically significant. Meanwhile, although treated cases did take longer to reach judgment, the offer of representation caused no increase in court burden as measured by other, more salient metrics, such as the number of party motions or the quantity of judicial rulings.
We discuss possible reasons for the magnitude of the differences between the outcomes experienced by the treated and control groups. For example, following previous work, we discuss the possible importance of the legal aid provider’s process for client recruitment and selection. Here, the provider invested substantial resources into a system designed to recruit and identify clients for whom unbundled legal assistance would be inadequate, suggesting that identifying such cases can be done but that doing so may be expensive. We conclude by discussing future directions for a movement, growing in momentum, toward an evidence-based approach for access to, and administration of, justice
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Propensity score methods for creating covariate balance in observational studies
Randomization of treatment assignment in experiments generates treatment groups with approximately balanced baseline covariates. However, in observational studies, where treatment assignment is not random, patients in the active treatment and control groups often differ on crucial covariates that are related to outcomes. These covariate imbalances can lead to biased treatment effect estimates. The propensity score is the probability that a patient with particular baseline characteristics is assigned to active treatment rather than control. Though propensity scores are unknown in observational studies, by matching or subclassifying patients on estimated propensity scores, we can design observational studies that parallel randomized experiments, with approximate balance on observed covariates. Observational study designs based on estimated propensity scores can generate approximately unbiased treatment effect estimates. Critically, propensity score designs should be created without access to outcomes, mirroring the separation of study design and outcome analysis in randomized experiments. This paper describes the potential outcomes framework for causal inference and best practices for designing observational studies with propensity scores. We discuss the use of propensity scores in two studies assessing the effectiveness and risks of antifibrinolytic drugs during cardiac surgery.Statistic
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Family-Based Treatment for Anorexia Nervosa Symptoms in High-Risk Youth: A Partially-Randomized Preference-Design Study
This pilot study adapted family-based treatment (FBT) for youth with potentially prodromal anorexia nervosa (AN). Fifty-nine youth with clinically significant AN symptom constellations, but who never met full Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) (DSM-IV) criteria for AN, were enrolled in a partially randomized preference design study. Participants were offered randomization to FBT or supportive psychotherapy (SPT); those who declined to be randomized because of a strong treatment preference were entered into a parallel, non-randomized self-selected intervention study. Without accessing outcome data, an observational analysis with three diagnostic subclasses was designed based on AN symptom severity profiles, combining randomized and non-randomized participants, such that participants receiving FBT and SPT within each subclass were similar on key baseline characteristics. Outcomes of this pilot study were explored by calculating effect sizes for end-of-treatment values within each subclass, and also with a longitudinal mixed effect model that accounted for subclass. Weight trajectory was measured by percent expected body weight. Psychological outcomes were fear of weight gain, feeling fat, importance of weight, and importance of shape. Results show that the pattern of symptom observations over time was dependent on subclass of SAN (least symptomatic, moderately symptomatic, or most symptomatic) and on the target outcome variable category (weight or psychological). Results from this study, which should be considered in the context of the small sample sizes overall and within groups, can generate hypotheses for future, larger research trials on early treatment strategies. Feasibility findings illustrate how the innovative partially randomized preference design has potential broader application for AN intervention research.Clinical trial registrationClinicalTrials.gov, identifier NCT00418977