INTEGRATE: Gene fusion discovery using whole genome and transcriptome data

While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use

Predicting Mid-Life Capital Formation with Pre-School Delay of Gratification and Life-Course Measures of Self-Regulation

How well do pre-school delay of gratification and life-course measures of self-regulation predict mid-life capital formation? We surveyed 113 participants of the 1967–1973 Bing pre-school studies on delay of gratification when they were in their late 40’s. They reported 11 mid-life capital formation outcomes, including net worth, permanent income, absence of high-interest debt, forward-looking behaviors, and educational attainment. To address multiple hypothesis testing and our small sample, we pre-registered an analysis plan of well–powered tests. As predicted, a newly constructed and pre-registered measure derived from preschool delay of gratification does not predict the 11 capital formation variables (i.e., the sign-adjusted average correlation was 0.02). A pre-registered composite self-regulation index, combining preschool delay of gratification with survey measures of self-regulation collected at ages 17, 27, and 37, does predict 10 of the 11 capital formation variables in the expected direction, with an average correlation of 0.19. The inclusion of the preschool delay of gratification measure in this composite index does not affect the index\u27s predictive power. We tested several hypothesized reasons that preschool delay of gratification does not have predictive power for our mid-life capital formation variables

Measuring nonuse damages using contingent valuation

This second edition of Measuring Nonuse Damages Using Conjoint Valuation is essentially a reprint of a 1992 monograph that has been in steady demand since its original appearance. The RTI Press edition, which is intended to meet continued inquiries and requests for the monograph, contains a Foreword and a Preface to the second edition that put the original work into historical perspective. These studies of ways to value stated preferences, as applied then to the Exxon Valdez oil spill, continue to be a timely and still-rigorous examination of such methods; even with the passage of time and statistical advances from the past two decades, the conclusions and insights as to whether and how these techniques might still be employed in valuing use or nonuse losses from similar events remain valid.Publishe

Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension

To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Loss of Neogenin perturbs AJs and attenuates junctional tension. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain and the WRC is crucial for the spatially restricted recruitment of the WRC to the junction. Thus, we provide the first example of a functional WIRS-WRC interaction in epithelia. We further show that Neogenin regulates cadherin recycling at the AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it influences both cadherin dynamics and junctional tension

The cryomechanical design of MUSIC: a novel imaging instrument for millimeter-wave astrophysics at the Caltech Submillimeter Observatory

MUSIC (Multicolor Submillimeter kinetic Inductance Camera) is a new facility instrument for the Caltech Submillimeter Observatory (Mauna Kea, Hawaii) developed as a collaborative effect of Caltech, JPL, the University of Colorado at Boulder and UC Santa Barbara, and is due for initial commissioning in early 2011. MUSIC utilizes a new class of superconducting photon detectors known as microwave kinetic inductance detectors (MKIDs), an emergent technology that offers considerable advantages over current types of detectors for submillimeter and millimeter direct detection. MUSIC will operate a focal plane of 576 spatial pixels, where each pixel is a slot line antenna coupled to multiple detectors through on-chip, lumped-element filters, allowing simultaneously imaging in four bands at 0.86, 1.02, 1.33 and 2.00 mm. The MUSIC instrument is designed for closed-cycle operation, combining a pulse tube cooler with a two-stage Helium-3 adsorption refrigerator, providing a focal plane temperature of 0.25 K with intermediate temperature stages at approximately 50, 4 and 0.4 K for buffering heat loads and heat sinking of optical filters. Detector readout is achieved using semi-rigid coaxial cables from room temperature to the focal plane, with cryogenic HEMT amplifiers operating at 4 K. Several hundred detectors may be multiplexed in frequency space through one signal line and amplifier. This paper discusses the design of the instrument cryogenic hardware, including a number of features unique to the implementation of superconducting detectors. Predicted performance data for the instrument system will also be presented and discussed

Outcome assessment after traumatic brain injury - Authors' reply

First paragraph: We thank Thomas McMillan and colleagues for their thoughtful comments on assessment of outcomes, with many of which we fully agree. As with many outcome assessments in traumatic brain injury (TBI), the Glasgow Outcome Scale (GOS) is open to a wide variety of influences other than brain injury: factors related to acute TBI appear to explain at best 35% of the variance.1 The predictors, moderators, and mediators of outcome after TBI are incompletely understood. There is thus much progress to be made in identifying confounding covariates for the effects of interventions. The current approach has many strengths, as pointed out by McMillan and colleagues. However, the GOS as originally proposed was quickly recognised to have limitations, and consequently has been adapted and improved over the years. The Extended Glasgow Outcome Scale (GOSE) structured interview was originally intended to help standardise assessment of outcomes, but there is still work to be done

Restrictive ID policies: implications for health equity

We wish to thank Synod Community Services for their critical work to develop, support, and implement a local government-issued ID in Washtenaw County, MI. We also thank Yousef Rabhi of the Michigan House of Representatives and Janelle Fa'aola of the Washtenaw ID Task Force, Lawrence Kestenbaum of the Washtenaw County Clerk's Office, Sherriff Jerry Clayton of the Washtenaw County Sherriff's Office, and the Washtenaw ID Task Force for their tireless commitment to developing and supporting the successful implementation of the Washtenaw ID. Additionally, we thank Vicenta Vargas and Skye Hillier for their contributions to the Washtenaw ID evaluation. We thank the Curtis Center for Research and Evaluation at the University of Michigan School of Social Work, the National Center for Institutional Diversity at the University of Michigan, and the University of California-Irvine Department of Chicano/Latino Studies and Program in Public Health for their support of the Washtenaw ID community-academic research partnership. Finally, we thank the reviewers for their helpful comments on earlier drafts of this manuscript. (Curtis Center for Research and Evaluation at the University of Michigan School of Social Work; National Center for Institutional Diversity at the University of Michigan; University of California-Irvine Department of Chicano/Latino Studies; Program in Public Health)https://link.springer.com/content/pdf/10.1007/s10903-017-0579-3.pdfPublished versio