Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Universality of interpersonal psychotherapy (IPT) problem areas in Thai depressed patients

<p>Abstract</p> <p>Background</p> <p>Many studies have shown the efficacy of interpersonal psychotherapy (IPT) on depression; however, there are limited studies concerning the universality of the IPT problem areas in different countries. This study identifies whether the interpersonal problem areas defined in the IPT manual are endorsed by Thai depressed patients.</p> <p>Methods</p> <p>The Thai Hamilton Rating Scale for Depression (Thai HRSD) and Thai Interpersonal Questionnaire were used to assess 90 depressed and 90 non-depressed subjects in King Chulalongkorn Memorial Hospital, during July 2007 - January 2008. The association between interpersonal problem areas/sociodemographic variables and depressive disorder were analyzed by chi-square test. A multivariable analysis was performed by using logistic regression to identify the remaining factors associated with depressive disorder.</p> <p>Results</p> <p>Most of the subjects were young to middle-aged females living in Bangkok and the Central Provinces. All four interpersonal problem areas (grief, interpersonal role disputes, role transitions, and interpersonal deficits) were increased in the depressed subjects as compared to the non-depressed subjects, as were the sociodemographic variables (low education, unemployment, low income, and having a physical illness). Logistic regression showed that all interpersonal problem areas still remained problems associated with depression (grief: adjusted OR = 6.01, 95%CI = 1.93 - 18.69, p < 0.01; interpersonal role disputes: adjusted OR = 6.01, 95%CI = 2.18 - 16.52, p < 0.01; role transitions: adjusted OR = 26.30, 95%CI = 7.84 - 88.25, p < 0.01; and interpersonal deficits: adjusted OR = 2.92, 95%CI = 1.12 - 7.60, p < 0.05).</p> <p>Conclusion</p> <p>All four interpersonal problem areas were applicable to Thai depressed patients.</p

Specialized ribosomes: integrating new insights and current challenges

Variation in the composition of different ribosomes, termed ribosome heterogeneity, is a now well established phenomenon. However, the functional implications of this heterogeneity on the regulation of protein synthesis are only now beginning to be revealed. While there are numerous examples of heterogeneous ribosomes, there are comparatively few bona fide specialized ribosomes described. Specialization requires that compositionally distinct ribosomes, through their subtly altered structure, have a functional consequence to the translational output. Even for those examples of ribosome specialization that have been characterized, the precise mechanistic details of how changes in protein and rRNA composition enable the ribosome to regulate translation are still missing. Here, we suggest looking at the evolution of specialization across the tree of life may help reveal central principles of translation regulation. We consider functional and structural studies that have provided insight into the potential mechanisms through which ribosome heterogeneity could affect translation, including through mRNA and open reading frame selectivity, elongation dynamics and post-translational folding. Further, we highlight some of the challenges that must be addressed to show specialization and review the contribution of various models. Several studies are discussed, including recent studies that show how structural insight is starting to shed light on the molecular details of specialization. Finally, we discuss the future of ribosome specialization studies, where advances in technology will likely enable the next wave of research questions. Recent work has helped provide a more comprehensive understanding of how ribosome heterogeneity affects translational control. This article is part of the discussion meeting issue ‘Ribosome diversity and its impact on protein synthesis, development and disease’

X-Ray Diffraction Measurement of Residual Stresses in Thick, Multi-Pass Steel Weldments

A unique X-ray diffraction instrument for residual stress measurement has been developed that provides for speed, ease of measurement, accuracy, and economy of surface stress measurement. Application of this instrument with a material removal technique, e.g., electropolishing, has facilitated detailed, high resolution studies of three-dimensional stress fields. This paper describes the instrumentation and techniques applied to conduct the residual stress measurement and presents maps of the residual stress data obtained for the surfaces of a heavy 2 1/4 Cr 1 Mo steel plate weldment.</jats:p

Identification of Novel Regulators of Hematopoietic Stem Cell Mobilization.

Abstract In an effort to identify the molecular changes during hematopoietic stem cell (HSC) mobilization we have analyzed genome wide changes in gene expression in HSCs in response to the chemotherapeutic agent cyclophosphamide (Cy) and the growth factor granulocyte colony stimulating factor (G). Cy/G treatment leads to an initial loss of proliferating precursors, followed by a rapid expansion of stem and progenitor cells and their migration to the peripheral blood. While this approach has been capitalized on for harvesting hematopoietic stem cells in clinical therapy, the molecular regulation of this process remains less well understood. To analyze changes in gene expression that occur in vivo as HSCs proliferate and prepare to migrate out of the bone marrow, we enriched for HSC fractions by isolating cells that express c-kit (K), Sca-1(S) and low levels of Thy1.1(T) but do not express lineage (L) markers (KTLS) from untreated mice and mice treated with Cy, G or Cy/G. The gene expression profile of these cells was examined by microarray analysis, relative to HSCs isolated from untreated mice. Interestingly, among the genes upregulated by Cy/G, a large majority (&amp;gt;60%) were a consequence of synergistic activity between Cy and G, while the rest of the upregulated genes could be attributed to activation by Cy or G alone. To test whether this screen allowed identification of novel candidates that regulate HSC function we analyzed the role of transforming growth factor beta induced gene (Big-h3), a gene highly upregulated after Cy/G treatment. Big-h3 is an extracellular matrix protein that mediates the adhesion and migration of various cell types, however its role in HSCs is unknown. Our experiments indicate that overexpression of Big-h3 in HSCs leads to enhanced adhesion to fibronectin as well as upregulation of specific integrins. These experiments suggest that changes in adhesion are an integral component of HSC mobilization, and that Big-h3 is one regulator of such processes. Further functional analysis of other candidates will likely lead to identification of other novel regulators of HSC development and mobilization.</jats:p