The SAMI Galaxy Survey: Cubism and covariance, putting round pegs into square holes

We present a methodology for the regularization and combination of sparse sampled and irregularly gridded observations from fibre-optic multiobject integral field spectroscopy. The approach minimizes interpolation and retains image resolution on combining subpixel dithered data. We discuss the methodology in the context of the Sydney-AAO multiobject integral field spectrograph (SAMI) Galaxy Survey underway at the Anglo-Australian Telescope. The SAMI instrument uses 13 fibre bundles to perform high-multiplex integral field spectroscopy across a 1° diameter field of view. The SAMI Galaxy Survey is targeting ~3000 galaxies drawn from the full range of galaxy environments. We demonstrate the subcritical sampling of the seeing and incomplete fill factor for the integral field bundles results in only a 10 per cent degradation in the final image resolution recovered. We also implement a new methodology for tracking covariance between elements of the resulting data cubes which retains 90 per cent of the covariance information while incurring only a modest increase in the survey data volume

Recombinant Newcastle disease viruses expressing immunological checkpoint inhibitors induce a pro-inflammatory state and enhance tumor-specific immune responses in two murine models of cancer

IntroductionTumor microenvironments are immunosuppressive due to progressive accumulation of mutations in cancer cells that can drive expression of a range of inhibitory ligands and cytokines, and recruitment of immunomodulatory cells, including myeloid-derived suppressor cells (MDSC), tumor-associated macrophages, and regulatory T cells (Tregs).MethodsTo reverse this immunosuppression, we engineered mesogenic Newcastle disease virus (NDV) to express immunological checkpoint inhibitors anti-cytotoxic T lymphocyte antigen-4 and soluble programmed death protein-1.ResultsIntratumoral administration of recombinant NDV (rNDV) to mice bearing intradermal B16-F10 melanomas or subcutaneous CT26LacZ colon carcinomas led to significant changes in the tumor-infiltrating lymphocyte profiles. Vectorizing immunological checkpoint inhibitors in NDV increased activation of intratumoral natural killer cells and cytotoxic T cells and decreased Tregs and MDSCs, suggesting induction of a pro-inflammatory state with greater infiltration of activated CD8+ T cells. These notable changes translated to higher ratios of activated effector/suppressor tumor-infiltrating lymphocytes in both cancer models, which is a promising prognostic marker. Whereas all rNDV-treated groups showed evidence of tumor regression and increased survival in the CT26LacZ and B16-F10, only treatment with NDV expressing immunological checkpoint blockades led to complete responses compared to tumors treated with NDV only.DiscussionThese data demonstrated that NDV expressing immunological checkpoint inhibitors could reverse the immunosuppressive state of tumor microenvironments and enhance tumor-specific T cell responses

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis

Background Naltrexone is an opioid antagonist used in many different conditions, both licensed and unlicensed. It is used at widely varying doses from 3 - 250 mg. The aim of this review was to evaluate the safety of oral naltrexone by examining the risk of serious adverse events (SAEs) in randomised controlled trials (RCTs) of naltrexone compared to placebo. Methods A systematic search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, other databases and clinical trials registries was undertaken up to March 2018. Parallel placebo-controlled RCTs longer than 4 weeks published after 1/1/2001, of oral naltrexone at any dose were selected. Any condition and age group were included, excluding only studies for opioid or ex-opioid users, due to possible opioid/opioid antagonist interactions. The systematic review used the guidance of the Cochrane Handbook throughout. Numerical data was independently extracted by two people and cross-checked. Risk of bias was assessed with the Cochrane Risk of Bias Tool. Meta-analyses were performed using Stata 15 and R, using random and fixed effects models throughout. Results Eighty-nine RCTs with 11194 participants were found, studying alcohol use disorders, various psychiatric disorders, impulse control disorders, other addictions, obesity, Crohn’s disease, fibromyalgia and cancers. Twenty-six studies (4,960 participants) recorded SAEs occurring by arm of study. There was no evidence of increased risk of SAEs for naltrexone compared to placebo, relative risk (RR) 0.84 (95% CI: 0.66 to 1.06). Sensitivity analyses pooling risk differences supported this conclusion (RD = -0.01 (-0.02, 0.00)) and subgroup analyses showed that results were consistent across different doses and disease groups. The quality of evidence for this outcome was judged high using the GRADE criteria. Conclusions Naltrexone does not appear to increase the risk of SAEs over placebo. These findings confirm the safety of naltrexone when used in licensed indications and encourage investments to undertake efficacy studies in unlicensed indications

Decentralized clinical trials in the trial innovation network: Value, strategies, and lessons learned

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology

The SAMI Galaxy Survey : data release one with emission-line physics value-added products

SAMI DR1 data products available from http://datacentral.aao.gov.au/asvo/surveys/sami/We present the first major release of data from the SAMI Galaxy Survey. This data release focuses on the emission-line physics of galaxies. Data Release One includes data for 772 galaxies, about 20% of the full survey. Galaxies included have the redshift range 0.004 <  z < 0.092, a large massrange (7.6 < log M∗/M⊙ < 11.6), and star-formation rates of ∼10−4 to ∼101 M⊙yr−1. For each galaxy, we include two spectral cubes and a set of spatially resolved 2D maps: single- and multi-component emission-line fits (with dust extinction corrections for strong lines), local dust extinction and star-formation rate. Calibration of the fibre throughputs, fluxes and differential-atmospheric-refraction has been improved over the Early Data Release. The data have average spatial resolution of 2.16 arcsec (FWHM) over the 15 arcsec diameter field of view and spectral (kinematic) resolution R= 4263 (σ= 30 km s−1) around Hα. The relative flux calibration is better than 5% and absolute flux calibration better than ±0.22 mag, with the latter estimate limited by galaxy photometry. The data are presented online through the Australian Astronomical Observatory’s Data Central.Publisher PDFPeer reviewe

The 6dF Galaxy Survey: the near-infrared Fundamental Plane of early-type galaxies

We determine the near-infrared Fundamental Plane (FP) for $\sim10^4$ early-type galaxies in the 6dF Galaxy Survey (6dFGS). We fit the distribution of central velocity dispersion, near-infrared surface brightness and half-light radius with a three-dimensional Gaussian model using a maximum likelihood method. For the 6dFGS $J$ band sample we find a FP with $R_{e}$\,$\propto$\,$\sigma_0^{1.52\pm0.03}I_{e}^{-0.89\pm0.01}$, similar to previous near-IR determinations and consistent with the $H$ and $K$ band Fundamental Planes once allowance is made for differences in mean colour. The overall scatter in $R_e$ about the FP is $\sigma_r$,=,29%, and is the quadrature sum of an 18% scatter due to observational errors and a 23% intrinsic scatter. Because of the distribution of galaxies in FP space, $\sigma_r$ is not the distance error, which we find to be $\sigma_d$,=,23%. Using group richness and local density as measures of environment, and morphologies based on visual classifications, we find that the FP slopes do not vary with environment or morphology. However, for fixed velocity dispersion and surface brightness, field galaxies are on average 5% larger than galaxies in higher-density environments, and the bulges of early-type spirals are on average 10% larger than ellipticals and lenticulars. The residuals about the FP show significant trends with environment, morphology and stellar population. The strongest trend is with age, and we speculate that age is the most important systematic source of offsets from the FP, and may drive the other trends through its correlations with environment, morphology and metallicity.Comment: 29 pages, 20 figures, accepted for publication in MNRAS. A version of this paper with fully interactive 3D figures, viewable with Adobe Reader 8.0 or higher, can be accessed from: http://www.aao.gov.au/6dFGS/Publications/REFEREED/fpfit_paper3d.pd

Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors

This study evaluates the prognostic significance of genetic abnormalities (detected at or shortly after presentation), clinical stage, lymphocyte morphology, CD38 expression, and IGVH gene status in 205 patients with chronic lymphocytic leukemia (B-CLL). Deletion of chromosome 11q23, absence of a deletion of chromosome 13q14, atypical lymphocyte morphology, and more than 30% CD38 expression are significantly associated with the presence of unmutated IGVH genes. Advanced stage, male sex, atypical morphology, more than 30% CD38 expression, trisomy 12, deletion of chromosome 11q23, loss or mutation of the p53 gene, and unmutated IGVH genes are all poor prognostic factors in a univariate analysis. However, only 98% or more homology of IGVH genes to the germline sequence, loss or mutation of the p53 gene, and clinical stage retain prognostic significance in a multivariate analysis. The median survival of patients with mutated IGVH genes, unmutated IGVH genes, and loss or mutation of the p53 gene regardless of IGVH gene status is 310, 119, and 47 months, respectively. These data should facilitate the design of new trials for the management of patients presenting with advanced disease or poor prognosis early stage disease