Intermittent hypoxia causes a form of serotonin-dependent synaptic plasticity in the spinal cord known as phrenic long-term facilitation (pLTF). Here we show that increased synthesis of brain-derived neurotrophic factor (BDNF) in the spinal cord is necessary and sufficient for pLTF in adult rats. We found that intermittent hypoxia elicited serotonin-dependent increases in BDNF synthesis in ventral spinal segments containing the phrenic nucleus, and the magnitude of these BDNF increases correlated with pLTF magnitude. We used RNA interference (RNAi) to interfere with BDNF expression, and tyrosine kinase receptor inhibition to block BDNF signaling. These disruptions blocked pLTF, whereas intrathecal injection of BDNF elicited an effect similar to pLTF. Our findings demonstrate new roles and regulatory mechanisms for BDNF in the spinal cord and suggest new therapeutic strategies for treating breathing disorders such as respiratory insufficiency after spinal injury. These experiments also illustrate the potential use of RNAi to investigate functional consequences of gene expression in the mammalian nervous system in vivo.

Objective. To test an intervention for improving self-management in rheumatoid arthritis (RA) using an online, cognitive-behavioral, self-management group program (RAHelp), with weekly telephone support. Methods. A 2-group, randomized study design was used to compare an intervention for RA versus a waiting-list control condition. The intervention used a secure web site (RAHelp.org) to provide a 10-week program with weekly educational modules for improving self-efficacy in self-management of RA, plus tools for group interaction. Weekly telephone contacts were made to encourage use of program tools and apply newly learned skills. A nationwide convenience sample of 106 adult participants (mean age 50 years, 93% women) was recruited primarily through online advertisements. Main outcome measures included the Arthritis Impact Measurement Scales 2 (affective, physical, role, social, and pain/ symptom components), Arthritis Self-Efficacy Scale (ASES), Center for Epidemiologic Studies Depression Scale, Quality of Life Scale (QLS), Rapid Assessment of Disease Activity in Rheumatology, Social Provisions Scale, and University of California, Los Angeles Loneliness Scale 3. Results. Group differences with large and moderate effect sizes (ES

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We make only one point in this article. Every quantitative study must be able to answer the question: what is your estimand? The estimand is the target quantity—the purpose of the statistical analysis. Much attention is already placed on how to do estimation; a similar degree of care should be given to defining the thing we are estimating. We advocate that authors state the central quantity of each analysis—the theoretical estimand—in precise terms that exist outside of any statistical model. In our framework, researchers do three things: (1) set a theoretical estimand, clearly connecting this quantity to theory; (2) link to an empirical estimand, which is informative about the theoretical estimand under some identification assumptions; and (3) learn from data. Adding precise estimands to research practice expands the space of theoretical questions, clarifies how evidence can speak to those questions, and unlocks new tools for estimation. By grounding all three steps in a precise statement of the target quantity, our framework connects statistical evidence to theory.