Make Research Data Public? -- Not Always so Simple: A Dialogue for Statisticians and Science Editors

Putting data into the public domain is not the same thing as making those data accessible for intelligent analysis. A distinguished group of editors and experts who were already engaged in one way or another with the issues inherent in making research data public came together with statisticians to initiate a dialogue about policies and practicalities of requiring published research to be accompanied by publication of the research data. This dialogue carried beyond the broad issues of the advisability, the intellectual integrity, the scientific exigencies to the relevance of these issues to statistics as a discipline and the relevance of statistics, from inference to modeling to data exploration, to science and social science policies on these issues.Comment: Published in at http://dx.doi.org/10.1214/10-STS320 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Microfluidic Device for On-Chip Immunophenotyping and Cytogenetic Analysis of Rare Biological Cells

This work is licensed under a Creative Commons Attribution 4.0 International License.The role of circulating plasma cells (CPCs) and circulating leukemic cells (CLCs) as biomarkers for several blood cancers, such as multiple myeloma and leukemia, respectively, have recently been reported. These markers can be attractive due to the minimally invasive nature of their acquisition through a blood draw (i.e., liquid biopsy), negating the need for painful bone marrow biopsies. CPCs or CLCs can be used for cellular/molecular analyses as well, such as immunophenotyping or fluorescence in situ hybridization (FISH). FISH, which is typically carried out on slides involving complex workflows, becomes problematic when operating on CLCs or CPCs due to their relatively modest numbers. Here, we present a microfluidic device for characterizing CPCs and CLCs using immunofluorescence or FISH that have been enriched from peripheral blood using a different microfluidic device. The microfluidic possessed an array of cross-channels (2–4 µm in depth and width) that interconnected a series of input and output fluidic channels. Placing a cover plate over the device formed microtraps, the size of which was defined by the width and depth of the cross-channels. This microfluidic chip allowed for automation of immunofluorescence and FISH, requiring the use of small volumes of reagents, such as antibodies and probes, as compared to slide-based immunophenotyping and FISH. In addition, the device could secure FISH results in <4 h compared to 2–3 days for conventional FISH

Structural discordance between neogene detachments and frontal Sevier thrusts, central Mormon Mountains, southern Nevada

Detailed geologic mapping in the Mormon Mountains of southern Nevada provides significant insight into processes of extensional tectonics developed within older compressional orogens. A newly discovered, WSW-directed low-angle normal fault, the Mormon Peak detachment, juxtaposes the highest levels of the frontal most part of the east-vergent, Mesozoic Sevier thrust belt with autochthonous crystalline basement. Palinspastic analysis suggests that the detachment initially dipped 20–25° to the west and cut discordantly across thrust faults. Nearly complete lateral removal of the hanging wall from the area has exposed a 5 km thick longitudinal cross-section through the thrust belt in the footwall, while highly attenuated remnants of the hanging wall (nowhere more than a few hundred meters thick) structurally veneer the range. The present arched configuration of the detachment resulted in part from progressive “domino-style” rotation of a few degrees while it was active, but is largely due to rotation on younger, structurally lower, basement-penetrating normal faults that initiated at high-angle. The geometry and kinematics of normal faulting in the Mormon Mountains suggest that pre-existing thrust planes are not required for the initiation of low-angle normal faults, and even where closely overlapped by extensional tectonism, need not function as a primary control of detachment geometry. Caution must thus be exercised in interpreting low-angle normal faults of uncertain tectonic heritage such as those seen in the COCORP west-central Utah and BIRP's MOIST deep-reflection profiles. Although thrust fault reactivation has reasonably been shown to be the origin of a very few low-angle normal faults, our results indicate that it may not be as fundamental a component of orogenic architecture as it is now widely perceived to be. We conclude that while in many instances thrust fault reactivation may be both a plausible and attractive hypothesis, it may never be assumed

A Cross-Lagged Panel Analysis of Fear Appeal Appraisal and Student Engagement

Background: Fear appeals are persuasive messages given by teachers to students about the importance of avoiding failure in an upcoming high-stakes test. The relationship between the way that students appraise fear appeals and engagement in lessons has not previously been tested using a robust methodological and analytical design that fully controls for concurrent relationships between the variables and stability over time. Aim: The present study addressed these limitations using a cross-lagged panel design to probe reciprocal relationships between students’ appraisal of fear appeals as a threat and as a challenge, with their engagement in class. Sample: A total of 2,025 Year 10 and 11 students took part. Method: Fear appeal appraisal and student engagement were measured at two time-points, four months apart. Results: After controlling for unlagged and auto-lagged correlations, and gender and year group, the model fit the data well and six cross-lagged paths emerged as statistically significant. Threat appraisal and emotional engagement were reciprocally, negatively related. Threat appraisal also positively predicted emotional disaffection and challenge appraisal negatively predicted behavioural disaffection. In addition, prospective relations were revealed between specific components of student engagement. Conclusions: Classroom teachers need to be aware of the possible consequences of making fear appeals and moderate this aspect of their practice accordingly. It would also be beneficial for educational interventions to focus on promoting challenge appraisals of fear appeals

One-loop calculations in quantum field theory: from Feynman diagrams to unitarity cuts

The success of the experimental program at the Tevatron re-inforced the idea that precision physics at hadron colliders is desirable and, indeed, possible. The Tevatron data strongly suggests that one-loop computations in QCD describe hard scattering well. Extrapolating this observation to the LHC, we conclude that knowledge of many short-distance processes at next-to-leading order may be required to describe the physics of hard scattering. While the field of one-loop computations is quite mature, parton multiplicities in hard LHC events are so high that traditional computational techniques become inefficient. Recently new approaches based on unitarity have been developed for calculating one-loop scattering amplitudes in quantum field theory. These methods are especially suitable for the description of multi-particle processes in QCD and are amenable to numerical implementations. We present a systematic pedagogical description of both conceptual and technical aspects of the new methods.Comment: 183 pages, 21 figures, 699 equations; published versio

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders