High-throughput profiling for discovery of non-coding RNA biomarkers of lung disease.

In respiratory medicine there is a need for clinical biomarkers for diagnosis, prognosis and assessment of response to therapy. Noncoding RNA (ncRNA) is expressed in all human cells; two major classes - long ncRNA and microRNA - are detectable extracellularly in the circulation and other biofluids. Altered ncRNA expression is associated with lung disease; collectively this indicates that ncRNA represents a potential biomarker class. This article presents and compares existing platforms for detection and quantification of ncRNA, specifically hybridization, qRT-PCR and RNA sequencing, and outlines methods for data interpretation and normalization. Each approach has merits and shortcomings, which can affect the choice of method when embarking on a biomarker study. Biomarker properties and pre-analytical considerations for ncRNA profiling are also presented. Since a variety of profiling approaches are available, careful study and experimental design are important. Finally, challenges and goals for reliable, standardized high-throughput ncRNA profiling in biofluids as lung disease biomarkers are reviewed

Chandra X-ray and Hubble Space Telescope Imaging of Optically Selected kiloparsec-Scale Binary Active Galactic Nuclei I. Nature of the Nuclear Ionizing Sources

Kiloparsec-scale binary active galactic nuclei (AGNs) signal active supermassive black hole (SMBH) pairs in merging galaxies. Despite their significance, unambiguously confirmed cases remain scarce and most have been discovered serendipitously. In a previous systematic search, we optically identified four kpc-scale binary AGNs from candidates selected with double-peaked narrow emission lines at redshifts of 0.1--0.2. Here we present Chandra and Hubble Space Telescope Wide Field Camera 3 (WFC3) imaging of these four systems. We critically examine and confirm the binary-AGN scenario for two of the four targets, by combining high angular resolution X-ray imaging spectroscopy with Chandra ACIS-S, better nuclear position constraints from WFC3 F105W imaging, and direct starburst estimates from WFC3 F336W imaging; for the other two targets, the existing data are still consistent with the binary-AGN scenario, but we cannot rule out the possibility of only one AGN ionizing gas in both merging galaxies. We find tentative evidence for a systematically smaller X-ray-to-[O III] luminosity ratio and/or higher Compton-thick fraction in optically selected kpc-scale binary AGNs than in single AGNs, possibly caused by a higher nuclear gas column due to mergers and/or a viewing angle bias related to the double-peak narrow line selection. While our result lends some further support to the general approach of optically identifying kpc-scale binary AGNs, it also highlights the challenge and ambiguity of X-ray confirmation.Comment: 18 emulateapj pages, 5 figures, ApJ in pres

Radio Properties of Low Redshift Broad Line Active Galactic Nuclei

The question as to whether the distribution of radio-loudness in active galactic nuclei (AGN) is actually bimodal has been discussed extensively in the literature. Futhermore, there have been claims that radio-loudness depends on black hole mass and Eddington ratio. We investigate these claims using the low redshift broad line AGN sample of Greene & Ho (2007), which consists of 8434 objects at z < 0.35 from the Sloan Digital Sky Survey Fourth Data Release (SDSS DR4). We obtained radio fluxes from the Very Large Array Faint Images of the Radio Sky at Twenty-Centimeters (FIRST) survey for the SDSS AGN. Out of the 8434 SDSS AGN, 821 have corresponding observed radio fluxes in the FIRST survey. We calculated the radio-loudness parameter (R) for all objects above the FIRST detection limit (1 mJy), and an upper limit to R for the undetected objects. Using these data, the question of radio bimodality is investigated for different subsets of the total sample. We find no clear demarcation between the radio-loud (RL, R > 10) and radio-quiet (RQ, R < 10) objects, but instead fill in a more radio-intermediate population in a continuous fashion for all subsamples. We find that 4.7% of the AGN in the flux-limited subsample are RL based on core radio emission alone. We calculate the radio-loud fraction (RLF) as both a function of black hole mass and Eddington ratio. The RLF decreases (from 13% to 2%) as Eddington ratio increases over 2.5 order of magnitude. The RLF is nearly constant (~5%) over 4 decades in black hole mass, except for an increase at masses greater than 10^8 solar masses. We find for the FIRST detected subsample that 367 of the RL AGN have black hole masses less than 10^8 solar masses, a large enough number to indicate that RL AGN are not a product of only the most massive black holes in the local universe.Comment: 28 pages, 14 figures, accepted to A

Non-coding RNA as lung disease biomarkers.

Biomarkers are quantifiable indicators of disease. These surrogates should be specific, sensitive, predictive, robust and easily accessible. A major class of RNA described as non-coding RNA fulfils many of these criteria, and recent studies have demonstrated that the two major subclasses of non-coding RNA, long non-coding RNA and, in particular, microRNA are promising potential biomarkers. The ability to detect non-coding RNAs in biofluids has highlighted their usefulness as non-invasive markers of lung disease. Because expression of specific non-coding RNAs is altered in many lung diseases and their levels in the circulation often reflect the changes in expression of their lung-specific counterparts, exploiting these biomolecules as diagnostic tools seems an obvious goal. New technology is driving developments in this area and there has been significant recent progress with respect to lung cancer diagnostics. The non-coding RNA biomarker field represents a clear example of modern-day bench-to-bedside research

Review of Downscaling Methodologies for Africa Climate Applications

Downscaling is the term used to describe the various methods used to translate the climate projections from coarse resolution GCMs to finer resolutions deemed more useful for assessing impacts. Projections of future climate are produced using complex, coupled atmosphere-ocean models (GCMs). The GCMs are most reliable at the continental scale. Due to the inherent uncertainty of the climate system and the inevitable existence of model errors, multi-model ensembling is the recommended approach for characterizing expected climate changes. As downscaling is dependent on the ability of GCMs to successfully project the climate change signal, it is limited to where that signal is clear. Assessments of climate change in Africa indicate some consensus of reduced winter rainfall in southern Africa, increased annual rainfall in east Africa and uncertainty for the rest of Africa. Selection of GCMs that "do better" over Africa, or any region, is difficult and probably not warranted, given the general parity in model skill and the difficulty in identifying which models are more skillful. Ensemble means or medians offer the highest level of projection accuracy. Downscaling approaches are generally categorized as dynamical, using regional climate models, and statistical, using empirical relationships. However, dynamical downscaling often includes statistical modeling in the form of "bias correction." Dynamical downscaling is useful for incorporating topographic features, such as strong orography, and land use and vegetation. It is recommended where those features play a significant role in regional climate. However, computational time and the uncertainties that accompany complex models outweigh the benefits of dynamical downscaling where these features are not significant. The spatial resolution that can be achieved is on the order of tens of kilometers. Statistical downscaling is simpler and more efficient than dynamical downscaling. It is preferred where estimates of specific variables, especially at point locations, are sought for input to sector models (e.g., hydrologic models) or decision making. However, statistical modeling can mask a true understanding of regional climate dynamics and estimates may be overconfident. In summary, downscaling is best understood as an attempt to increase the understanding of climate change influences at the regional scale. In that context, a variety of methodologies should be explored, using all tools possible to increase that understanding. A set of "Best Practices" is recommended for pursuing this effort

The Case of Ty Jackson: An Interactive Module on LGBT Health Employing Introspective Techniques and Video-Based Case Discussion

Introduction: The Institute of Medicine's 2011 report on lesbian, gay, bisexual, and transgender (LGBT) health and the legalization of same-sex marriage are just two of the numerous milestones that have hastened medical schools' efforts to prepare trainees to address the needs of LGBT community members. Early awareness of sexual diversity through self- and peer introspection and video-based education can help trainees build a foundation towards providing affirming care to LGBT patients. Methods: The Kern model was used to develop, implement, and evaluate an interactive multimodal workshop to provide first-year medical students with a formative introduction to LGBT health. Learning objectives focused on comprehending the spectrum of human sexuality, health issues for LGBT patients, and better practices for promoting affirming care. The module consisted of a PowerPoint presentation, sexuality survey, videos of provider-patient encounters, and community-based resources. Results: The workshop was implemented among 178 first-year medical students in September 2018, with 93% completing the pre-/postworkshop evaluations. Comparison of evaluations showed an increase in confidence in addressing each of the three learning objectives. Over 85% rated the PowerPoint and videos as very good or excellent. Discussion: This workshop was effective in helping first-year medical students appreciate the spectrum of sexual diversity, health issues facing LGBT individuals, and better practices to promote affirming care. The real-time sexuality survey helped trainees appreciate sexual diversity through self-reflection and near-peer sharing. The videos and accompanying discussion provided real-life encounters, along with common pitfalls in and pearls for communicating with LGBT patients

Education Freedom and Student Achievement: Is More School Choice Associated with Higher State-Level Performance on the NAEP?

School choice is on the rise in many states. Since the start of the new millennium, many states have launched or expanded private school choice options, permitted and expanded independently operated public charter schools, eased restrictions on homeschooling, and enacted policies that allow and encourage various forms of public school choice. One thing that is not on the rise, unfortunately, is average student scores on the National Assessment of Education Progress (NAEP). Student performance on the assessments, typically called “The Nation’s Report Card,” were flat from 2001 until 2015 and have dropped slightly in both 2017 and 2019

The disappearance of the "revolving door" patient in Scottish general practice: successful policies

&lt;b&gt;Background&lt;/b&gt; We describe the health of "revolving door" patients in general practice in Scotland, estimate changes in their number over the timescale of the study, and explore reasons for changes, particularly related to NHS and government policy.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A mixed methods predominantly qualitative study, using a grounded theory approach, set in Scottish general practice. Semi-structured interviews were conducted with professional key informants, 6 Practitioner Services staff who administer the GP registration system and 6 GPs with managerial or clinical experience of working with "revolving door" patients. Descriptive statistical analysis and qualitative analysis of patient removal episodes linked with routine hospital admissions, outpatient appointments, drug misuse treatment episodes and deaths were carried out with cohorts of "revolving door" patients identified from 1999 to 2005 in Scotland.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; A "revolving door" patient is removed 4 or more times from GP lists in 7 years. Patients had complex health issues including substance misuse, psychiatric and physical health problems and were at high risk of dying. There was a dramatic reduction in the number of "revolving door" patients during the course of the study.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; "Revolving door" patients in general practice had significant health problems. Their numbers have reduced dramatically since 2004 and this probably resulted from improved drug treatment services, pressure from professional bodies to reduce patient removals and the positive ethical regulatory and financial climate of the 2004 GMS GP contract. This is a positive development for the NHS

The effects of inhomogeneities on the cosmology of type IIB conifold transitions

In this paper we examine the evolution of the effective field theory describing a conifold transition in type IIB string theory. Previous studies have considered such dynamics starting from the cosmological approximation of homogeneous fields, here we include the effects of inhomogeneities by using a real-time lattice field theory simulation. By including spatial variations we are able to simulate the effect of currents and the gauge fields which they source. We identify two different regimes where the inhomogeneities have opposite effects, one where they aid the system to complete the conifold transition and another where they hinder it. The existence of quantized fluxes in related systems has lead to the speculation that (unstable) string solutions could exist, using our simulations we give strong evidence that these string-like defects do not form.Comment: 11 pages, 2 figures. Published versio