Showing papers by "Ohio State University published in 2007"

Addressing Moderated Mediation Hypotheses: Theory, Methods, and Prescriptions.

Abstract: This article provides researchers with a guide to properly construe and conduct analyses of conditional indirect effects, commonly known as moderated mediation effects. We disentangle conflicting definitions of moderated mediation and describe approaches for estimating and testing a variety of hypotheses involving conditional indirect effects. We introduce standard errors for hypothesis testing and construction of confidence intervals in large samples but advocate that researchers use bootstrapping whenever possible. We also describe methods for probing significant conditional indirect effects by employing direct extensions of the simple slopes method and Johnson-Neyman technique for probing significant interactions. Finally, we provide an SPSS macro to facilitate the implementation of the recommended asymptotic and bootstrapping methods. We illustrate the application of these methods with an example drawn from the Michigan Study of Adolescent Life Transitions, showing that the indirect effect of intrinsic student interest on mathematics performance through teacher perceptions of talent is moderated by student math self-concept.

The Shuttle Radar Topography Mission

Abstract: [1] The Shuttle Radar Topography Mission produced the most complete, highest-resolution digital elevation model of the Earth. The project was a joint endeavor of NASA, the National Geospatial-Intelligence Agency, and the German and Italian Space Agencies and flew in February 2000. It used dual radar antennas to acquire interferometric radar data, processed to digital topographic data at 1 arc sec resolution. Details of the development, flight operations, data processing, and products are provided for users of this revolutionary data set.

Answering the Call for a Standard Reliability Measure for Coding Data

Abstract: In content analysis and similar methods, data are typically generated by trained human observers who record or transcribe textual, pictorial, or audible matter in terms suitable for analysis. Conclusions from such data can be trusted only after demonstrating their reliability. Unfortunately, the content analysis literature is full of proposals for so-called reliability coefficients, leaving investigators easily confused, not knowing which to choose. After describing the criteria for a good measure of reliability, we propose Krippendorff's alpha as the standard reliability measure. It is general in that it can be used regardless of the number of observers, levels of measurement, sample sizes, and presence or absence of missing data. To facilitate the adoption of this recommendation, we describe a freely available macro written for SPSS and SAS to calculate Krippendorff's alpha and illustrate its use with a simple example.

The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions

Abstract: Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.

Expanding the utilization of sustainable plant products in aquafeeds: a review

Abstract: Continued growth and intensi¢cation of aquaculture production depends upon the development of sustainable protein sources to replace ¢sh meal in aquafeeds. This document reviews various plant feedstuis, which currently are or potentially may be incorporated into aquafeeds to support the sustainable production of various ¢sh species in aquaculture. The plant feedstuis considered include oilseeds, legumes and cereal grains, which traditionally have been used as protein or energy concentrates as well as novel products developed through various processing technologies. The nutritional composition of these various feedstuis are considered along with the presence of any bioactive compounds that may positively or negatively aiect the target organism. Lipid composition of these feedstuis is not speci¢cally considered although it is recognized that incorporating lipid supplements in aquafeeds to achieve proper fatty acid pro¢les to meet the metabolic requirements of ¢sh and maximize human health bene¢ts are important aspects. Speci¢c strategies and techniques to optimize the nutritional composition of plant feedstuis and limit potentially adverse eiects of bioactive compounds are also described. Such information will provide a foundation for developing strategic research plans for increasing the use of plant feedstuis in aquaculture to reduce dependence of animal feedstuis and thereby enhance the sustainability of aquaculture.

MicroRNA-133 controls cardiac hypertrophy

Abstract: Growing evidence indicates that microRNAs (miRNAs or miRs) are involved in basic cell functions and oncogenesis. Here we report that miR-133 has a critical role in determining cardiomyocyte hypertrophy. We observed decreased expression of both miR-133 and miR-1, which belong to the same transcriptional unit, in mouse and human models of cardiac hypertrophy. In vitro overexpression of miR-133 or miR-1 inhibited cardiac hypertrophy. In contrast, suppression of miR-133 by 'decoy' sequences induced hypertrophy, which was more pronounced than that after stimulation with conventional inducers of hypertrophy. In vivo inhibition of miR-133 by a single infusion of an antagomir caused marked and sustained cardiac hypertrophy. We identified specific targets of miR-133: RhoA, a GDP-GTP exchange protein regulating cardiac hypertrophy; Cdc42, a signal transduction kinase implicated in hypertrophy; and Nelf-A/WHSC2, a nuclear factor involved in cardiogenesis. Our data show that miR-133, and possibly miR-1, are key regulators of cardiac hypertrophy, suggesting their therapeutic application in heart disease.

MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B.

Abstract: MicroRNAs (miRNAs) are small, noncoding RNAs that regulate expression of many genes. Recent studies suggest roles of miRNAs in carcinogenesis. We and others have shown that expression profiles of miRNAs are different in lung cancer vs. normal lung, although the significance of this aberrant expression is poorly understood. Among the reported down-regulated miRNAs in lung cancer, the miRNA (miR)-29 family (29a, 29b, and 29c) has intriguing complementarities to the 3′-UTRs of DNA methyltransferase (DNMT)3A and -3B (de novo methyltransferases), two key enzymes involved in DNA methylation, that are frequently up-regulated in lung cancer and associated with poor prognosis. We investigated whether miR-29s could target DNMT3A and -B and whether restoration of miR-29s could normalize aberrant patterns of methylation in non-small-cell lung cancer. Here we show that expression of miR-29s is inversely correlated to DNMT3A and -3B in lung cancer tissues, and that miR-29s directly target both DNMT3A and -3B. The enforced expression of miR-29s in lung cancer cell lines restores normal patterns of DNA methylation, induces reexpression of methylation-silenced tumor suppressor genes, such as FHIT and WWOX, and inhibits tumorigenicity in vitro and in vivo. These findings support a role of miR-29s in epigenetic normalization of NSCLC, providing a rationale for the development of miRNA-based strategies for the treatment of lung cancer.

The Trouble With Overconfidence

Abstract: This paper presents a reconciliation of the three distinct ways in which the research literature has defined overconfidence: (1) overestimation of one's actual performance, (2) overplacement of one's performance relative to others, and (3) excessive precision in one's beliefs. Experimental evidence shows that reversals of the first two (apparent underconfidence), when they occur, tend to be on different types of tasks. On difficult tasks, people overestimate their actual performances but also believe that they are worse than others; on easy tasks, people underestimate their actual performances but believe they are better than others. This paper offers a straightforward theory that can explain these inconsistencies. Overprecision appears to be more persistent than either of the other two types of overconfidence, but its presence reduces the magnitude of both overestimation and overplacement.

Ab initio calculation of ideal strength and phonon instability of graphene under tension

Abstract: Graphene-based $s{p}^{2}$-carbon nanostructures such as carbon nanotubes and nanofibers can fail near their ideal strengths due to their exceedingly small dimensions. We have calculated the phonon spectra of graphene as a function of uniaxial tension by density functional perturbation theory to assess the first occurrence of phonon instability on the strain path, which controls the strength of a defect-free crystal at $0\phantom{\rule{0.3em}{0ex}}\mathrm{K}$. Uniaxial tensile strain is applied in the $x$ (nearest-neighbor) and $y$ (second nearest-neighbor) directions, related to tensile deformation of zigzag and armchair nanotubes, respectively. The Young's modulus $E=1050\phantom{\rule{0.3em}{0ex}}\mathrm{GPa}$ and Poisson's ratio $\ensuremath{ u}=0.186$ from our small-strain results are in good agreement with previous calculations. We find that in both $x$ and $y$ uniaxial tensions, phonon instabilities occur near the center of the Brillouin zone, at (${\ensuremath{\epsilon}}_{xx}=0.194$, ${\ensuremath{\sigma}}_{xx}=110\phantom{\rule{0.3em}{0ex}}\mathrm{GPa}$, ${\ensuremath{\epsilon}}_{yy}=\ensuremath{-}0.016$) and (${\ensuremath{\epsilon}}_{yy}=0.266$, ${\ensuremath{\sigma}}_{yy}=121\phantom{\rule{0.3em}{0ex}}\mathrm{GPa}$, ${\ensuremath{\epsilon}}_{xx}=\ensuremath{-}0.027$), respectively. Both soft phonons are longitudinal elastic waves in the pulling direction, suggesting that brittle cleavage fracture may be an inherent behavior of graphene and carbon nanotubes at low temperatures. We also predict that a phonon band gap will appear in highly stretched graphene, which could be a useful spectroscopic signature for highly stressed carbon nanotubes.

Modulation of miR-155 and miR-125b Levels following Lipopolysaccharide/TNF-α Stimulation and Their Possible Roles in Regulating the Response to Endotoxin Shock

Abstract: We report here that miR-155 and miR-125b play a role in innate immune response. LPS stimulation of mouse Raw 264.7 macrophages resulted in the up-regulation of miR-155 and down-regulation of miR-125b levels. The same changes also occurred when C57BL/6 mice were i.p. injected with LPS. Furthermore, the levels of miR-155 and miR-125b in Raw 264.7 cells displayed oscillatory changes in response to TNF-alpha. These changes were impaired by pretreating the cells with the proteasome inhibitor MG-132, suggesting that these two microRNAs (miRNAs) may be at least transiently under the direct control of NF-kappaB transcriptional activity. We show that miR-155 most probably directly targets transcript coding for several proteins involved in LPS signaling such as the Fas-associated death domain protein (FADD), IkappaB kinase epsilon (IKKepsilon), and the receptor (TNFR superfamily)-interacting serine-threonine kinase 1 (Ripk1) while enhancing TNF-alpha translation. In contrast, miR-125b targets the 3'-untranslated region of TNF-alpha transcripts; therefore, its down-regulation in response to LPS may be required for proper TNF-alpha production. Finally, Emu-miR-155 transgenic mice produced higher levels of TNF-alpha when exposed to LPS and were hypersensitive to LPS/d-galactosamine-induced septic shock. Altogether, our data suggest that the LPS/TNF-alpha-dependent regulation of miR-155 and miR-125b may be implicated in the response to endotoxin shock, thus offering new targets for drug design.

Regression with missing Ys: An improved strategy for analyzing multiply imputed data

Abstract: When fitting a generalized linear model—such as linear regression, logistic regression, or hierarchical linear modeling—analysts often wonder how to handle missing values of the dependent variable Y. If missing values have been filled in using multiple imputation, the usual advice is to use the imputed Y values in analysis. We show, however, that using imputed Ys can add needless noise to the estimates. Better estimates can usually be obtained using a modified strategy that we call multiple imputation, then deletion (MID). Under MID, all cases are used for imputation but, following imputation, cases with imputed Y values are excluded from the analysis. When there is something wrong with the imputed Y values, MID protects the estimates from the problematic imputations. And when the imputed Y values are acceptable, MID usually offers somewhat more efficient estimates than an ordinary MI strategy.

MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis.

Abstract: ContextWhile global microRNA (miRNA) expression patterns of many embryologic, physiologic, and oncogenic processes have been described, description of the role of miRNAs in ductal adenocarcinoma of the pancreas is lacking.ObjectiveTo define the expression pattern of miRNAs in pancreatic cancer and compare it with those of normal pancreas and chronic pancreatitis.Design and SettingSpecimens were obtained at a National Cancer Institute–designated comprehensive cancer center from patients with ductal adenocarcinoma of the pancreas (n = 65) or chronic pancreatitis (n = 42) (January 2000-December 2005). All patients underwent curative pancreatectomy; those with pancreatic cancer were chemotherapy-naive. RNA harvested from resected pancreatic cancers and matched benign adjacent pancreatic tissue as well as from chronic pancreatitis specimens was hybridized to miRNA microarrays.Main Outcome MeasuresIdentification of differentially expressed miRNAs that could differentiate pancreatic cancer from normal pancreas, chronic pancreatitis, or both, as well as a pattern of miRNA expression predictive of long-term (>24 months) survival. Significance of Analysis of Microarrays and Prediction of Analysis of Microarrays were undertaken to identify miRNAs predictive of tissue type and prognosis. P values were calculated by t test, adjusted for multiple testing. Kaplan-Meier survival curves were constructed using mean miRNA expression (high vs low) as threshold and compared by log-rank analysis.ResultsTwenty-one miRNAs with increased expression and 4 with decreased expression were identified that correctly differentiated pancreatic cancer from benign pancreatic tissue in 90% of samples by cross validation. Fifteen overexpressed and 8 underexpressed miRNAs differentiated pancreatic cancer from chronic pancreatitis with 93% accuracy. A subgroup of 6 miRNAs was able to distinguish long-term survivors with node-positive disease from those dying within 24 months. Finally, high expression of miR-196a-2 was found to predict poor survival (median, 14.3 months [95% confidence interval, 12.4-16.2] vs 26.5 months [95% confidence interval, 23.4-29.6]; P = .009).ConclusionsPancreatic cancer may have a distinct miRNA expression pattern that may differentiate it from normal pancreas and chronic pancreatitis. miRNA expression patterns may be able to distinguish between long- and short-term survivors, but these findings need to be validated in other study populations.

A 160-kilobit molecular electronic memory patterned at 10 11 bits per square centimetre

Abstract: The primary metric for gauging progress in the various semiconductor integrated circuit technologies is the spacing, or pitch, between the most closely spaced wires within a dynamic random access memory (DRAM) circuit. Modern DRAM circuits have 140 nm pitch wires and a memory cell size of 0.0408 mum(2). Improving integrated circuit technology will require that these dimensions decrease over time. However, at present a large fraction of the patterning and materials requirements that we expect to need for the construction of new integrated circuit technologies in 2013 have 'no known solution'. Promising ingredients for advances in integrated circuit technology are nanowires, molecular electronics and defect-tolerant architectures, as demonstrated by reports of single devices and small circuits. Methods of extending these approaches to large-scale, high-density circuitry are largely undeveloped. Here we describe a 160,000-bit molecular electronic memory circuit, fabricated at a density of 10(11) bits cm(-2) (pitch 33 nm; memory cell size 0.0011 microm2), that is, roughly analogous to the dimensions of a DRAM circuit projected to be available by 2020. A monolayer of bistable, [2]rotaxane molecules served as the data storage elements. Although the circuit has large numbers of defects, those defects could be readily identified through electronic testing and isolated using software coding. The working bits were then configured to form a fully functional random access memory circuit for storing and retrieving information.

A MicroRNA Signature of Hypoxia

Abstract: Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these noncoding transcripts. Here, we demonstrate for the first time a functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression. Microarray-based expression profiles revealed that a specific spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210, and -213) is induced in response to low oxygen, at least some via a hypoxia-inducible-factor-dependent mechanism. Select members of this group (miR-26, -107, and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation. Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.

Pre-b cell proliferation and lymphoblastic leukemia/high-grade lymphoma in mir155 transgenic mice

Abstract: A transgenic non-human animal, such as a mouse, has a genome that include a nucleic acid construct having at least one transcriptional regulatory sequence capable of directing expression in B cells of the animal, wherein the transcriptional regulatory sequence is operably linked to a nucleic acid encoding a miR155 gene product. A method of testing the therapeutic efficacy of an agent in treating or preventing a lymphoproliferative condition includes assessing the effect(s) of the agent on a transgenic non-human animal.

Observational Constraints on the Nature of Dark Energy: First Cosmological Results from the ESSENCE Supernova Survey

Abstract: We present constraints on the dark energy equation-of-state parameter, w = P/(rho c(2)), using 60 SNe Ia fromthe ESSENCE supernova survey. We derive a set of constraints on the nature of the dark energy assuming a flat universe. By including constraints on (Omega(M), w) from baryon acoustic oscillations, we obtain a value for a static equation-of-state parameter w = -1:05(-0.12)(+0: 13) (stat 1 sigma) +/- 0: 13 (sys) and Omega(M) = 0:274(-0.020)(+0:033) (stat 1 sigma) with a bestfit chi(2)/dof of 0.96. These results are consistent with those reported by the Supernova Legacy Survey from the first year of a similar program measuring supernova distances and redshifts. We evaluate sources of systematic error that afflict supernova observations and present Monte Carlo simulations that explore these effects. Currently, the largest systematic with the potential to affect our measurements is the treatment of extinction due to dust in the supernova host galaxies. Combining our set of ESSENCE SNe Ia with the first-results Supernova Legacy Survey SNe Ia, we obtain a joint constraint of w = -1:07(-0: 09)(+0:09) (stat 1 sigma) +/- 0: 13 ( sys), Omega(M) 0:267(-0:028)(+0:028) (stat 1 sigma) with a best-fit chi(2)/dof of 0.91. The current global SN Ia data alone rule out empty (Omega(M) = 0), matter-only Omega(M) = 0: 3, and Omega(M) = 1 universes at > 4.5 sigma. The current SN Ia data are fully consistent with a cosmological constant.

CMS physics technical design report, volume II: Physics performance

Abstract: CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking--through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb−1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z' and supersymmetric particles, Bs production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb−1 to 30 fb−1. The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing ET, B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model

Chemistry of deep-fat frying oils

Abstract: Deep-fat frying produces desirable or undesirable flavor compounds and changes the flavor stability and quality of the oil by hydrolysis, oxidation, and polymerization. Tocopherols, essential amino acids, and fatty acids in foods are degraded during deep-fat frying. The reactions in deep-fat frying depend on factors such as replenishment of fresh oil, frying conditions, original quality of frying oil, food materials, type of fryer, antioxidants, and oxygen concentration. High frying temperature, the number of fryings, the contents of free fatty acids, polyvalent metals, and unsaturated fatty acids of oil decrease the oxidative stability and flavor quality of oil. Antioxidant decreases the frying oil oxidation, but the effectiveness of antioxidant decreases with high frying temperature. Lignan compounds in sesame oil are effective antioxidants in deep-fat frying.

Inconsistency of phylogenetic estimates from concatenated data under coalescence.

Abstract: Although multiple gene sequences are becoming increasingly available for molecular phylogenetic inference, the analysis of such data has largely relied on inference methods designed for single genes. One of the common approaches to analyzing data from multiple genes is concatenation of the individual gene data to form a single supergene to which traditional phylogenetic inference procedures - e.g., maximum parsimony (MP) or maximum likelihood (ML) - are applied. Recent empirical studies have demonstrated that concatenation of sequences from multiple genes prior to phylogenetic analysis often results in inference of a single, well-supported phylogeny. Theoretical work, however, has shown that the coalescent can produce substantial variation in single-gene histories. Using simulation, we combine these ideas to examine the performance of the concatenation approach under conditions in which the coalescent produces a high level of discord among individual gene trees and show that it leads to statistically inconsistent estimation in this setting. Furthermore, use of the bootstrap to measure support for the inferred phylogeny can result in moderate to strong support for an incorrect tree under these conditions. These results highlight the importance of incorporating variation in gene histories into multilocus phylogenetics.

Using heteroskedasticity-consistent standard error estimators in OLS regression: an introduction and software implementation.

Abstract: Homoskedasticity is an important assumption in ordinary least squares (OLS) regression. Although the estimator of the regression parameters in OLS regression is unbiased when the homoskedasticity assumption is violated, the estimator of the covariance matrix of the parameter estimates can be biased and inconsistent under heteroskedasticity, which can produce significance tests and confidence intervals that can be liberal or conservative. After a brief description of heteroskedasticity and its effects on inference in OLS regression, we discuss a family of heteroskedasticity-consistent standard error estimators for OLS regression and argue investigators should routinely use one of these estimators when conducting hypothesis tests using OLS regression. To facilitate the adoption of this recommendation, we provide easy-to-use SPSS and SAS macros to implement the procedures discussed here.

Limits on the Macho Content of the Galactic Halo from the EROS-2 Survey of the Magellanic Clouds

Abstract: The EROS-2 project was designed to test the hypothesis that massive compact halo objects (the so-called ''machos'') could be a major component of the dark matter halo of the Milky Way galaxy. To this end, EROS-2 monitored millions of stars in the Magellanic clouds for microlensing events caused by such objects. (abridged)

Clinical Response and Risk for Reported Suicidal Ideation and Suicide Attempts in Pediatric Antidepressant Treatment: A Meta-analysis of Randomized Controlled Trials

Abstract: ContextThe US Food and Drug Administration (FDA) has issued warnings that use of antidepressant medications poses a small but significantly increased risk of suicidal ideation/suicide attempt for children and adolescents.ObjectiveTo assess the efficacy and risk of reported suicidal ideation/suicide attempt of antidepressants for treatment of pediatric major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders.Data Sources and Study SelectionPubMed (1988 to July 2006), relevant US and British regulatory agency reports, published abstracts of important scientific meetings (1998-2006), clinical trial registries, and information from authors. Studies were published and unpublished randomized, placebo-controlled, parallel-group trials of second-generation antidepressants (selective serotonin reuptake inhibitors, nefazodone, venlafaxine, and mirtazapine) in participants younger than 19 years with MDD, OCD, or non-OCD anxiety disorders.Data ExtractionInformation was extracted on study characteristics, efficacy outcomes, and spontaneously reported suicidal ideation/suicide attempt.Data SynthesisTwenty-seven trials of pediatric MDD (n = 15), OCD (n = 6), and non-OCD anxiety disorders (n = 6) were selected, and risk differences for response and for suicidal ideation/suicide attempt estimated by random-effects methods. Pooled risk differences in rates of primary study-defined measures of responder status significantly favored antidepressants for MDD (11.0%; [95% confidence interval {CI}, 7.1% to 14.9%]), OCD (19.8% [95% CI, 13.0% to 26.6%), and non-OCD anxiety disorders (37.1% [22.5% to 51.7%]), corresponding to a number needed to treat (NNT) of 10 (95% CI, 7 to 15), 6 (4 to 8), and 3 (2 to 5), respectively. While there was increased risk difference of suicidal ideation/suicide attempt across all trials and indications for drug vs placebo (0.7%; 95% CI, 0.1% to 1.3%) (number needed to harm, 143 [95% CI, 77 to 1000]), the pooled risk differences within each indication were not statistically significant: 0.9% (95% CI, −0.1% to 1.9%) for MDD, 0.5% (−1.2% to 2.2%) for OCD, and 0.7% (−0.4% to 1.8%) for non-OCD anxiety disorders. There were no completed suicides. Age-stratified analyses showed that for children younger than 12 years with MDD, only fluoxetine showed benefit over placebo. In MDD trials, efficacy was moderated by age, duration of depression, and number of sites in the treatment trial.ConclusionsRelative to placebo, antidepressants are efficacious for pediatric MDD, OCD, and non-OCD anxiety disorders, although the effects are strongest in non-OCD anxiety disorders, intermediate in OCD, and more modest in MDD. Benefits of antidepressants appear to be much greater than risks from suicidal ideation/suicide attempt across indications, although comparison of benefit to risk varies as a function of indication, age, chronicity, and study conditions.