Second-generation p-values: improved rigor, reproducibility, & transparency in statistical analyses

Verifying that a statistically significant result is scientifically meaningful is not only good scientific practice, it is a natural way to control the Type I error rate. Here we introduce a novel extension of the p-value - a second-generation p-value - that formally accounts for scientific relevance and leverages this natural Type I Error control. The approach relies on a pre-specified interval null hypothesis that represents the collection of effect sizes that are scientifically uninteresting or are practically null. The second-generation p-value is the proportion of data-supported hypotheses that are also null hypotheses. As such, second-generation p-values indicate when the data are compatible with null hypotheses, or with alternative hypotheses, or when the data are inconclusive. Moreover, second-generation p-values provide a proper scientific adjustment for multiple comparisons and reduce false discovery rates. This is an advance for environments rich in data, where traditional p-value adjustments are needlessly punitive. Second-generation p-values promote transparency, rigor and reproducibility of scientific results by a priori specifying which candidate hypotheses are practically meaningful and by providing a more reliable statistical summary of when the data are compatible with alternative or null hypotheses.Comment: 29 pages, 29 page Supplemen

Early Science with the Large Millimetre Telescope: Molecules in the Extreme Outflow of a proto-Planetary Nebula

Extremely high velocity emission likely related to jets is known to occur in some proto-Planetary Nebulae. However, the molecular complexity of this kinematic component is largely unknown. We observed the known extreme outflow from the proto-Planetary Nebula IRAS 16342-3814, a prototype water fountain, in the full frequency range from 73 to 111 GHz with the RSR receiver on the Large Millimetre Telescope. We detected the molecules SiO, HCN, SO, and $^{13}$CO. All molecular transitions, with the exception of the latter are detected for the first time in this source, and all present emission with velocities up to a few hundred km s$^{-1}$. IRAS 16342-3814 is therefore the only source of this kind presenting extreme outflow activity simultaneously in all these molecules, with SO and SiO emission showing the highest velocities found of these species in proto-Planetary Nebulae. To be confirmed is a tentative weak SO component with a FWHM $\sim$ 700 km s$^{-1}$. The extreme outflow gas consists of dense gas (n$_{\rm H_2} >$ 10$^{4.8}$--10$^{5.7}$ cm$^{-3}$), with a mass larger than $\sim$ 0.02--0.15 M$_{\odot}$. The relatively high abundances of SiO and SO may be an indication of an oxygen-rich extreme high velocity gas.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Society Letter

Dynamics and Thermodynamics of Systems with Long Range Interactions: an Introduction

We review theoretical results obtained recently in the framework of statistical mechanics to study systems with long range forces. This fundamental and methodological study leads us to consider the different domains of applications in a trans-disciplinary perspective (astrophysics, nuclear physics, plasmas physics, metallic clusters, hydrodynamics,...) with a special emphasis on Bose-Einstein condensates.Comment: Chapter of the forthcoming "Lecture Notes in Physics" volume: ``Dynamics and Thermodynamics of Systems with Long Range Interactions'', T. Dauxois, S. Ruffo, E. Arimondo, M. Wilkens Eds., Lecture Notes in Physics Vol. 602, Springer (2002). (see http://link.springer.de/series/lnpp/

Engagement of basal amygdala‐nucleus accumbens glutamate neurons in the processing of rewarding or aversive social stimuli

Basal amygdala (BA) neurons projecting to nucleus accumbens (NAc) core/shell are primarily glutamatergic and are integral to the circuitry of emotional processing. Several recent mouse studies have addressed whether neurons in this population(s) respond to reward, aversion or both emotional valences. The focus has been on processing of physical emotional stimuli, and here, we extend this to salient social stimuli. In male mice, an iterative study was conducted into engagement of BA‐NAc neurons in response to estrous female (social reward, SR) and/or aggressive‐dominant male (social aversion, SA). In BL/6J mice, SR and SA activated c‐Fos expression in a high and similar number/density of BA‐NAc neurons in the anteroposterior intermediate BA (int‐BA), whereas activation was predominantly by SA in posterior (post‐)BA. In Fos‐TRAP2 mice, compared with SR‐SR or SA‐SA controls, exposure to successive presentation of SR‐SA or SA‐SR, followed by assessment of tdTomato reporter and/or c‐Fos expression, demonstrated that many int‐BA‐NAc neurons were activated by only one of SR and SA; these SR/SA monovalent neurons were similar in number and present in both magnocellular and parvocellular int‐BA subregions. In freely moving BL/6J mice exposed to SR, bulk GCaMP6 fibre photometry provided confirmatory in vivo evidence for engagement of int‐BA‐NAc neurons during social and sexual interactions. Therefore, populations of BA‐NAc glutamate neurons are engaged by salient rewarding and aversive social stimuli in a topographic and valence‐specific manner; this novel evidence is important to the overall understanding of the roles of this pathway in the circuitry of socio‐emotional processing

LMT/AzTEC observations of Vega

Vega is the prototypical debris disc system. Its architecture has been extensively studied at optical to millimetre wavelengths, revealing a near face-on, broad, and smooth disc with multiple distinct components. Recent millimetre-wavelength observations from ALMA spatially resolved the inner edge of the outer, cold planetesimal belt from the star for the first time. Here we present early science imaging observations of the Vega system with the AzTEC instrument on the 32-m LMT, tracing extended emission from the disc out to 150 au from the star. We compare the observations to three models of the planetesimal belt architecture to better determine the profile of the outer belt. A comparison of these potential architectures for the disc does not significantly differentiate between them with the modelling results being similar in many respects to the previous ALMA analysis, but differing in the slope of the outer region of the disc. The measured flux densities are consistent between the LMT (single dish) and ALMA (interferometric) observations after accounting for the differences in wavelength of observation. The LMT observations suggest the outer slope of the planetesimal belt is steeper than was suggested in the ALMA analysis. This would be consistent with the interferometric observations being mostly blind to structure at the disc outer edges, but the overall low signal to noise of the LMT observations does not definitively resolve the structure of the outer planetesimal belt.FK and JPM acknowledge research support by the Ministry of Science and Technology of Taiwan under grant MOST107-2119-M-001-031-MY3, and Academia Sinica under grant AS-IA-106-M03. JPM acknowledges research support by the Ministry of Science and Technology of Taiwan under grant MOST109-2112-M-001-036-MY3. MC thanks Consejo Nacional de Ciencia y Tecnología (CONACyT) for financial support through grant CB-2015-256961

Search for galactic axions with a high-Q dielectric cavity

A haloscope of the QUAX--$a\gamma$ experiment, composed of an high-Q resonant cavity immersed in a 8 T magnet and cooled to $\sim 4.5$~K is operated to search for galactic axion with mass $m_a\simeq42.8~\mu\text{eV}$. The design of the cavity with hollow dielectric cylinders concentrically inserted in a OFHC Cu cavity, allowed us to maintain a loaded quality-factor Q $\sim 300000$ during the measurements in presence of magnetic field. Through the cavity tuning mechanism it was possible to modulate the resonance frequency of the haloscope in the region $10.35337-10.35345$~GHz and thus acquire different dataset at different resonance frequencies. Acquiring each dataset for about 50 minutes, combining them and correcting for the axion's signal estimation-efficiency we set a limit on the axion-photon coupling $g_{a\gamma\gamma}< 0.731\times10^{-13}$ GeV$^{-1}$ with the confidence level set at $90\%$

The clumpy structure of ϵ\epsilon Eridani's debris disc revisited by ALMA

$\epsilon$ Eridani is the closest star to our Sun known to host a debris disc. Prior observations in the (sub-)millimetre regime have potentially detected clumpy structure in the disc and attributed this to interactions with an (as yet) undetected planet. However, the prior observations were unable to distinguish between structure in the disc and background confusion. Here we present the first ALMA image of the entire disc, which has a resolution of 1.6"$\times$1.2". We clearly detect the star, the main belt and two point sources. The resolution and sensitivity of this data allow us to clearly distinguish background galaxies (that show up as point sources) from the disc emission. We show that the two point sources are consistent with background galaxies. After taking account of these, we find that resolved residuals are still present in the main belt, including two clumps with a $>3\sigma$ significance -- one to the east of the star and the other to the northwest. We perform $n$-body simulations to demonstrate that a migrating planet can form structures similar to those observed by trapping planetesimals in resonances. We find that the observed features can be reproduced by a migrating planet trapping planetesimals in the 2:1 mean motion resonance and the symmetry of the most prominent clumps means that the planet should have a position angle of either ${\sim10^\circ}$ or ${\sim190^\circ}$. Observations over multiple epochs are necessary to test whether the observed features rotate around the star.Comment: 16 pages, 10 figures, accepted for publication in MNRA

MAPlex: A massively parallel sequencing ancestry analysis multiplex for Asia-Pacific populations

© 2019 The Authors Current forensic ancestry-informative panels are limited in their ability to differentiate populations in the Asia-Pacific region. MAPlex (Multiplex for the Asia-Pacific), a massively parallel sequencing (MPS) assay, was developed to improve differentiation of East Asian, South Asian and Near Oceanian populations found in the extensive cross-continental Asian region that shows complex patterns of admixture at its margins. This study reports the development of MAPlex; the selection of SNPs in combination with microhaplotype markers; assay design considerations for reducing the lengths of microhaplotypes while preserving their ancestry-informativeness; adoption of new population-informative multiple-allele SNPs; compilation of South Asian-informative SNPs suitable for forensic AIMs panels; and the compilation of extensive reference and test population genotypes from online whole-genome-sequence data for MAPlex markers. STRUCTURE genetic clustering software was used to gauge the ability of MAPlex to differentiate a broad set of populations from South and East Asia, the West Pacific regions of Near Oceania, as well as the other globally distributed population groups. Preliminary assessment of MAPlex indicates enhanced South Asian differentiation with increased divergence between West Eurasian, South Asian and East Asian populations, compared to previous forensic SNP panels of comparable scale. In addition, MAPlex shows efficient differentiation of Middle Eastern individuals from Europeans. MAPlex is the first forensic AIM assay to combine binary and multiple-allele SNPs with microhaplotypes, adding the potential to detect and analyze mixed source forensic DNA

Effects of the dose of erythropoiesis stimulating agents on cardiovascular events, quality of life, and health-related costs in hemodialysis patients: the clinical evaluation of the dose of erythropoietins (C.E. DOSE) trial protocol

<p>Abstract</p> <p>Background</p> <p>Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.</p> <p>Methods/Design</p> <p>This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.</p> <p>Discussion</p> <p>The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00827021</p

Defining the genetic control of human blood plasma N-glycome using genome-wide association study

Glycosylation is a common post-translational modification of proteins. Glycosylation is associated with a number of human diseases. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting with the 36 original traits measured by UPLC, we computed an additional 77 derived traits leading to a total of 113 glycan traits. We studied associations between these traits and genetic polymorphisms located on human autosomes. We discovered and replicated 12 loci. This allowed us to demonstrate an overlap in genetic control between total plasma protein and IgG glycosylation. The majority of revealed loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3 and MGAT5) and a known regulator of plasma protein fucosylation (HNF1A). However, we also found loci that could possibly reflect other more complex aspects of glycosylation process. Functional genomic annotation suggested the role of several genes including DERL3, CHCHD10, TMEM121, IGH and IKZF1. The hypotheses we generated may serve as a starting point for further functional studies in this research area