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 Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g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

Discourses of student orientation to medical education programs

Background: Although medical students’ initial orientation is an important point of transition in medical education, there is a paucity of literature on the subject and major variations in the ways that different institutions orient incoming medical students to their programs. Methods: We conducted a discourse analysis of medical education orientation in the literature and on data from a survey of peer institutions’ approaches to orientation. Results: These two discourses of orientation had clear similarities, in particular, the critical role of ceremony and symbols, and the focus on developing professionalism and physician identities. There were also differences between them, in particular, in the way that the discourse in the literature focused on the symbolic and professional aspects of orientation; something we have called ‘cultural orientation’. Meanwhile, those who were responsible for orientation in their own institutions tended to focus on the practical and social dimensions. Conclusion: By examining how orientation has been described and discussed, we identify three domains of orientation: cultural, social, and practical. These domains are relatively distinct in terms of the activities associated with them, and in terms of who is involved in organizing and running these activities. We also describe orientation as a liminal activity system on the threshold of medical school where incoming students initially cross into the profession. Interestingly, this state of ambiguity also extends to the scholarship of orientation with only some of its aspects attracting formal enquiry, even though there is a growing interest in transitions in medical education as a whole. We hope, therefore, that this study can help to legitimize enquiry into orientation in all its forms and that it can begin to situate the role of orientation more firmly within the firmament of medical education practice and research

The effect of increasing the supply of skilled health providers on pregnancy and birth outcomes: evidence from the midwives service scheme in Nigeria

Background: Limited availability of skilled health providers in developing countries is thought to be an important barrier to achieving maternal and child health-related MDG goals. Little is known, however, about the extent to which scaling-up supply of health providers will lead to improved pregnancy and birth outcomes. We study the effects of the Midwives Service Scheme (MSS), a public sector program in Nigeria that increased the supply of skilled midwives in rural communities on pregnancy and birth outcomes. Methods: We surveyed 7,104 women with a birth within the preceding five years across 12 states in Nigeria and compared changes in birth outcomes in MSS communities to changes in non-MSS communities over the same period. Results: The main measured effect of the scheme was a 7.3-percentage point increase in antenatal care use in program clinics and a 5-percentage point increase in overall use of antenatal care, both within the first year of the program. We found no statistically significant effect of the scheme on skilled birth attendance or on maternal delivery complications. Conclusion: This study highlights the complexity of improving maternal and child health outcomes in developing countries, and shows that scaling up supply of midwives may not be sufficient on its own

A theoretical model for template-free synthesis of long DNA sequence

This theoretical scheme is intended to formulate a potential method for high fidelity synthesis of Nucleic Acid molecules towards a few thousand bases using an enzyme system. Terminal Deoxyribonucleotidyl Transferase, which adds a nucleotide to the 3′OH end of a Nucleic Acid molecule, may be used in combination with a controlled method for nucleotide addition and degradation, to synthesize a predefined Nucleic Acid sequence. A pH control system is suggested to regulate the sequential activity switching of different enzymes in the synthetic scheme. Current practice of synthetic biology is cumbersome, expensive and often error prone owing to the dependence on the ligation of short oligonucleotides to fabricate functional genetic parts. The projected scheme is likely to render synthetic genomics appreciably convenient and economic by providing longer DNA molecules to start with

Sec12 Binds to Sec16 at Transitional ER Sites

COPII vesicles bud from an ER domain known as the transitional ER (tER). Assembly of the COPII coat is initiated by the transmembrane guanine nucleotide exchange factor Sec12. In the budding yeast Pichia pastoris, Sec12 is concentrated at tER sites. Previously, we found that the tER localization of P. pastoris Sec12 requires a saturable binding partner. We now show that this binding partner is Sec16, a peripheral membrane protein that functions in ER export and tER organization. One line of evidence is that overexpression of Sec12 delocalizes Sec12 to the general ER, but simultaneous overexpression of Sec16 retains overexpressed Sec12 at tER sites. Additionally, when P. pastoris Sec12 is expressed in S. cerevisiae, the exogenous Sec12 localizes to the general ER, but when P. pastoris Sec16 is expressed in the same cells, the exogenous Sec12 is recruited to tER sites. In both of these experimental systems, the ability of Sec16 to recruit Sec12 to tER sites is abolished by deleting a C-terminal fragment of Sec16. Biochemical experiments confirm that this C-terminal fragment of Sec16 binds to the cytosolic domain of Sec12. Similarly, we demonstrate that human Sec12 is concentrated at tER sites, likely due to association with a C-terminal fragment of Sec16A. These results suggest that a Sec12–Sec16 interaction has a conserved role in ER export

Utilizing high-throughput experimentation to enhance specific productivity of an E.coli T7 expression system by phosphate limitation

<p>Abstract</p> <p>Background</p> <p>The specific productivity of cultivation processes can be optimized, amongst others, by using genetic engineering of strains, choice of suitable host/vector systems or process optimization (e.g. choosing the right induction time). A further possibility is to reduce biomass buildup in favor of an enhanced product formation, e.g. by limiting secondary substrates in the medium, such as phosphate. However, with conventional techniques (e.g. small scale cultivations in shake flasks), it is very tedious to establish optimal conditions for cell growth and protein expression, as the start of protein expression (induction time) and the degree of phosphate limitation have to be determined in numerous concerted, manually conducted experiments.</p> <p>Results</p> <p>We investigated the effect of different induction times and a concurrent phosphate limitation on the specific productivity of the T7 expression system <it>E.coli </it>BL21(DE3) pRhotHi-2-EcFbFP, which produces the model fluorescence protein EcFbFP upon induction. Therefore, specific online-monitoring tools for small scale cultivations (RAMOS, BioLector) as well as a novel cultivation platform (Robo-Lector) were used for rapid process optimization. The RAMOS system monitored the oxygen transfer rate in shake flasks, whereas the BioLector device allowed to monitor microbial growth and the production of EcFbFP in microtiter plates. The Robo-Lector is a combination of a BioLector and a pipetting robot and can conduct high-throughput experiments fully automated. By using these tools, it was possible to determine the optimal induction time and to increase the specific productivity for EcFbFP from 22% (for unlimited conditions) to 31% of total protein content of the <it>E.coli </it>cells via a phosphate limitation.</p> <p>Conclusions</p> <p>The results revealed that a phosphate limitation at the right induction time was suitable to redirect the available cellular resources during cultivation to protein expression rather than in biomass production. To our knowledge, such an effect was shown for the first time for an IPTG-inducible expression system. Finally, this finding and the utilization of the introduced high-throughput experimentation approach could help to find new targets to further enhance the production capacity of recombinant <it>E.coli</it>-strains.</p

Advancing the argument for validity of the Alberta Context Tool with healthcare aides in residential long-term care

<p>Abstract</p> <p>Background</p> <p>Organizational context has the potential to influence the use of new knowledge. However, despite advances in understanding the theoretical base of organizational context, its measurement has not been adequately addressed, limiting our ability to quantify and assess context in healthcare settings and thus, advance development of contextual interventions to improve patient care. We developed the Alberta Context Tool (the ACT) to address this concern. It consists of 58 items representing 10 modifiable contextual concepts. We reported the initial validation of the ACT in 2009. This paper presents the second stage of the psychometric validation of the ACT.</p> <p>Methods</p> <p>We used the <it>Standards for Educational and Psychological Testing </it>to frame our validity assessment. Data from 645 English speaking healthcare aides from 25 urban residential long-term care facilities (nursing homes) in the three Canadian Prairie Provinces were used for this stage of validation. In this stage we focused on: (1) advanced aspects of internal structure (e.g., confirmatory factor analysis) and (2) relations with other variables validity evidence. To assess reliability and validity of scores obtained using the ACT we conducted: Cronbach's alpha, confirmatory factor analysis, analysis of variance, and tests of association. We also assessed the performance of the ACT when individual responses were aggregated to the care unit level, because the instrument was developed to obtain unit-level scores of context.</p> <p>Results</p> <p>Item-total correlations exceeded acceptable standards (> 0.3) for the majority of items (51 of 58). We ran three confirmatory factor models. Model 1 (all ACT items) displayed unacceptable fit overall and for five specific items (1 item on <it>adequate space for resident care </it>in the Organizational Slack-Space ACT concept and 4 items on use of electronic resources in the Structural and Electronic Resources ACT concept). This prompted specification of two additional models. Model 2 used the 7 scaled ACT concepts while Model 3 used the 3 count-based ACT concepts. Both models displayed substantially improved fit in comparison to Model 1. Cronbach's alpha for the 10 ACT concepts ranged from 0.37 to 0.92 with 2 concepts performing below the commonly accepted standard of 0.70. Bivariate associations between the ACT concepts and instrumental research utilization levels (which the ACT should predict) were statistically significant at the 5% level for 8 of the 10 ACT concepts. The majority (8/10) of the ACT concepts also showed a statistically significant trend of increasing mean scores when arrayed across the lowest to the highest levels of instrumental research use.</p> <p>Conclusions</p> <p>The validation process in this study demonstrated additional empirical support for construct validity of the ACT, when completed by healthcare aides in nursing homes. The overall pattern of the data was consistent with the structure hypothesized in the development of the ACT and supports the ACT as an appropriate measure for assessing organizational context in nursing homes. Caution should be applied in using the one space and four electronic resource items that displayed misfit in this study with healthcare aides until further assessments are made.</p