The unified protocol for transdiagnostic treatment of emotional disorders compared with diagnosis-specific protocols for anxiety disorders a randomized clinical trial

IMPORTANCE: Transdiagnostic interventions have been developed to address barriers to the dissemination of evidence-based psychological treatments, but only a few preliminary studies have compared these approaches with existing evidence-based psychological treatments. OBJECTIVE: To determine whether the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as efficacious as single-disorder protocols (SDPs) in the treatment of anxiety disorders. DESIGN, SETTING, AND PARTICIPANTS: From June 23, 2011, to March 5, 2015, a total of 223 patients at an outpatient treatment center with a principal diagnosis of panic disorder with or without agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, or social anxiety disorder were randomly assigned by principal diagnosis to the UP, an SDP, or a waitlist control condition. Patients received up to 16 sessions of the UP or an SDP for 16 to 21 weeks. Outcomes were assessed at baseline, after treatment, and at 6-month follow-up. Analysis in this equivalence trial was based on intention to treat. INTERVENTIONS: The UP or SDPs. MAIN OUTCOMES AND MEASURES: Blinded evaluations of principal diagnosis clinical severity rating were used to evaluate an a priori hypothesis of equivalence between the UP and SDPs. RESULTS: Among the 223 patients (124 women and 99 men; mean [SD] age, 31.1 [11.0] years), 88 were randomized to receive the UP, 91 to receive an SDP, and 44 to the waitlist control condition. Patients were more likely to complete treatment with the UP than with SDPs (odds ratio, 3.11; 95% CI, 1.44-6.74). Both the UP (Cohen d, −0.93; 95% CI, −1.29 to −0.57) and SDPs (Cohen d, −1.08; 95% CI, −1.43 to −0.73) were superior to the waitlist control condition at acute outcome. Reductions in clinical severity rating from baseline to the end of treatment (β, 0.25; 95% CI, −0.26 to 0.75) and from baseline to the 6-month follow-up (β, 0.16; 95% CI, −0.39 to 0.70) indicated statistical equivalence between the UP and SDPs. CONCLUSIONS AND RELEVANCE: The UP produces symptom reduction equivalent to criterion standard evidence-based psychological treatments for anxiety disorders with less attrition. Thus, it may be possible to use 1 protocol instead of multiple SDPs to more efficiently treat the most commonly occurring anxiety and depressive disorders.This study was funded by grant R01 MH090053 from the National Institute of Mental Health. (R01 MH090053 - National Institute of Mental Health)First author draf

What Would I Know About Mercy? Faith and Optimistic Expectancies Among African Americans

A small body of research has begun to explore the association between faith and optimism among African Americans. However, missing from the extant work is an examination of the extent to which traditional indices of religious commitment work together with beliefs about God to shape optimism. The present study examines the utility of indices of social location, religious commitment (i.e., early and current religious service attendance, subjective religiosity), belief about the quality of one’s relationship with God (i.e., a belief that one is connected to a loving God), and beliefs about being the recipient of divine forgiveness for predicting dispositional optimism among a sample of community residing African American adults (N = 241). Age, subjective religiosity, and organizational religiosity were positively related to optimism in bivariate analyses. Hierarchical regression analyses demonstrated a significant association between age, subjective religiosity, and optimism; however, those associations were eliminated once relationship with God and belief in one’s forgiveness by God were entered into the model. Only belief in God’s love predicted optimism in multivariate analyses. Serial mediation analyses revealed that beliefs about the quality of one’s relationship with God and belief in divine forgiveness fully mediated the relationship between subjective religiosity and optimism, but that the relationship is driven largely by relationship with God. Implications of these findings are discussed

Protecting Astronaut Medical Privacy: Review of Presentations and Publications for Attributability

Retrospective research and medical data collected on astronauts can be a valuable resource for researchers. This data can be requested from two separate NASA Archives. The Lifetime Surveillance of Astronaut Health (LSAH) holds astronaut medical data, and the Life Sciences Data Archive (LSDA) holds research data. One condition of use of astronaut research and medical data is the requirement that all abstracts, publications and presentations using this data must be reviewed for attributability. All final versions of abstracts, presentations, posters, and manuscripts must be reviewed by LSDA/LSAH prior to submission to a conference, journal, or other entities outside the Principal Investigator (PI) laboratory [including the NASA Export Control Document Availability Authorization (DAA) system]. If material undergoes multiple revisions (e.g., journal editor comments), the new versions must also be reviewed by LSDA/LSAH prior to re-submission to the journal. The purpose of this review is to ensure that no personally identifiable information (PII) is included in materials that are presented in a public venue or posted to the public domain. The procedures for submitting materials for review will be outlined. The process that LSAH/LSDA follows for assessing attributability will be presented. Characteristics and parameter combinations that often prompt attributability concerns will be identified. A published case report for a National Football League (NFL) player will be used to demonstrate how, in a population of public interest, a combination of information can result in inadvertent release of private or sensitive information

Characterization of renal cell carcinoma-associated constitutional chromosome abnormalities by genome sequencing.

Constitutional translocations, typically involving chromosome 3, have been recognized as a rare cause of inherited predisposition to renal cell carcinoma (RCC) for four decades. However, knowledge of the molecular basis of this association is limited. We have characterized the breakpoints by genome sequencing (GS) of constitutional chromosome abnormalities in five individuals who presented with RCC. In one individual with constitutional t(10;17)(q11.21;p11.2), the translocation breakpoint disrupted two genes: the known renal tumor suppressor gene (TSG) FLCN (and clinical features of Birt-Hogg-Dubé syndrome were detected) and RASGEF1A. In four cases, the rearrangement breakpoints did not disrupt known inherited RCC genes. In the second case without chromosome 3 involvement, the translocation breakpoint in an individual with a constitutional t(2;17)(q21.1;q11.2) mapped 12 Kb upstream of NLK. Interestingly, NLK has been reported to interact indirectly with FBXW7 and a previously reported RCC-associated translocation breakpoint disrupted FBXW7. In two cases of constitutional chromosome 3 translocations, no candidate TSGs were identified in the vicinity of the breakpoints. However, in an individual with a constitutional chromosome 3 inversion, the 3p breakpoint disrupted the FHIT TSG (which has been reported previously to be disrupted in two apparently unrelated families with an RCC-associated t(3;8)(p14.2;q24.1). These findings (a) expand the range of constitutional chromosome rearrangements that may be associated with predisposition to RCC, (b) confirm that chromosome rearrangements not involving chromosome 3 can predispose to RCC, (c) suggest that a variety of molecular mechanisms are involved the pathogenesis of translocation-associated RCC, and (d) demonstrate the utility of GS for investigating such cases

Halobacteriovorax, an underestimated predator on bacteria: potential impact relative to viruses on bacterial mortality

Predation on bacteria and accompanying mortality are important mechanisms in controlling bacterial populations and recycling of nutrients through the microbial loop. The agents most investigated and seen as responsible for bacterial mortality are viruses and protists. However, a body of evidence suggests that predatory bacteria such as the Halobacteriovorax (formerly Bacteriovorax), a Bdellovibrio-like organism, contribute substantially to bacterial death. Until now, conclusive evidence has been lacking. The goal of this study was to better understand the contributors to bacterial mortality by addressing the poorly understood role of Halobacteriovorax and how their role compares with that of viruses. The results revealed that when a concentrated suspension of Vibrio parahaemolyticus was added into microcosms of estuarine waters, the native Halobacteriovorax were the predators that responded first and most rapidly. Their numbers increased by four orders of magnitude, whereas V. parahaemolyticus prey numbers decreased by three orders of magnitude. In contrast, the extant virus population showed little increase and produced little change in the prey density. An independent experiment with stable isotope probing confirmed that Halobacteriovorax were the predators primarily responsible for the mortality of the V. parahaemolyticus. The results show that Halobacteriovorax have the potential to be significant contributors to bacterial mortality, and in such cases, predation by Halobacteriovorax may be an important mechanism of nutrient recycling. These conclusions add another dimension to bacterial mortality and the recycling of nutrients

Whole genome analysis for 163 gRNAs in Cas9-edited mice reveals minimal off-target activity.

Genome editing with CRISPR-associated (Cas) proteins holds exceptional promise for correcting variants causing genetic disease. To realize this promise, off-target genomic changes cannot occur during the editing process. Here, we use whole genome sequencing to compare the genomes of 50 Cas9-edited founder mice to 28 untreated control mice to assess the occurrence of S. pyogenes Cas9-induced off-target mutagenesis. Computational analysis of whole-genome sequencing data detects 26 unique sequence variants at 23 predicted off-target sites for 18/163 guides used. While computationally detected variants are identified in 30% (15/50) of Cas9 gene-edited founder animals, only 38% (10/26) of the variants in 8/15 founders validate by Sanger sequencing. In vitro assays for Cas9 off-target activity identify only two unpredicted off-target sites present in genome sequencing data. In total, only 4.9% (8/163) of guides tested have detectable off-target activity, a rate of 0.2 Cas9 off-target mutations per founder analyzed. In comparison, we observe ~1,100 unique variants in each mouse regardless of genome exposure to Cas9 indicating off-target variants comprise a small fraction of genetic heterogeneity in Cas9-edited mice. These findings will inform future design and use of Cas9-edited animal models as well as provide context for evaluating off-target potential in genetically diverse patient populations

Erratum: Author Correction: Identification of genes required for eye development by high-throughput screening of mouse knockouts.

[This corrects the article DOI: 10.1038/s42003-018-0226-0.]

Trio-Based GWAS Identifies Novel Associations and Subtype-Specific Risk Factors for Cleft Palate

Cleft palate (CP) is one of the most common craniofacial birth defects; however, there are relatively few established genetic risk factors associated with its occurrence despite high heritability. Historically, CP has been studied as a single phenotype, although it manifests across a spectrum of defects involving the hard and/or soft palate. We performed a genome-wide association study using transmission disequilibrium tests of 435 case-parent trios to evaluate broad risks for any cleft palate (ACP) (n = 435), and subtype-specific risks for any cleft soft palate (CSP), (n = 259) and any cleft hard palate (CHP) (n = 125). We identified a single genome-wide significant locus at 9q33.3 (lead SNP rs7035976, p = 4.24 × 1