Alignment-free sequence comparison for biologically realistic sequences of moderate length

The D2 statistic, defined as the number of matches of words of some pre-specified length k, is a computationally fast alignment-free measure of biological sequence similarity. However there is some debate about its suitability for this purpose as the variability in D2 may be dominated by the terms that reflect the noise in each of the single sequences only. We examine the extent of the problem and the effectiveness of overcoming it by using two mean-centred variants of this statistic, D2* and D2c. We conclude that all three statistics are potentially useful measures of sequence similarity, for which reasonably accurate p-values can be estimated under a null hypothesis of sequences composed of identically and independently distributed letters. We show that D2 and D2c, and to a somewhat lesser extent D2*, perform well in tests to classify moderate length query sequences as putative cis-regulatory modules.This work was funded in part by ARC discovery grant DP098729

Controlling false discovery rates in RNA-Sequencing data

High throughput sequencing technologies are supplanting microarrays as the preferred technology for detecting and quantifying differential gene expression. The raw data produced by the a technique known as RNA-sequencing (RNA-seq), consists of integer counts of reverse transcribed cDNA fragment reads mapped onto each gene or transcript isoform in a reference genome or transcriptome. Many software packages exist for analysing RNA-seq datasets consisting of tables of mapped read counts from biological or technical replicate experiments under two or more conditions, the purpose being to detect which genes are differentially expressed between conditions. Two state-of-the-art packages, DESeq and edgeR, are based on a negative binomial model of read counts. Our tests with simulated data constructed according to the statistical model assumed by these packages reveal that both packages generate a non-uniform p-value spectrum from null-hypothesis data. We demo! nstrate how specific knowledge of the non-uniformity can be exploited to develop a graphical technique based on the Storey-Tibshirani method for improving estimates of p-values and false discovery rates in databases where differential expression is present. We have developed an add-on package for DESeq and edgeR, called Polyfit, which implements this method, and evaluate its performance against DESeq, edgeR and another recently introduced package, PoissonSeq, using simulated data

Valuing Compromise for the Common Good

Pursuing the common good in a pluralist democracy is not possible without making compromises. Yet the spirit of compromise is in short supply in contemporary American politics. The permanent campaign has made compromise more difficult to achieve, as the uncompromising mindset suitable for campaigning has come to dominate the task of governing. To begin to make compromise more feasible and the common good more attainable, we need to appreciate the distinctive value of compromise and recognize the misconceptions that stand in its way. A common mistake is to assume that compromise requires finding the common ground on which all can agree. That undermines more realistic efforts to seek classic compromises, in which each party gains by sacrificing something valuable to the other, and together they serve the common good by improving upon the status quo. Institutional reforms are desirable, but they, too, cannot get off the ground without the support of leaders and citizens who learn how and when to adopt a compromising mindset

Multi-dimensional analysis, text constellations, and interdisciplinary discourse

Multi-Dimensional Analysis (MDA) has been widely used to explore register variation. This paper reports on a project using MDA to explore the features of an interdisciplinary academic domain. Six dimensions of variation are identified in a corpus of 11,000 journal articles in environmental studies. We then focus on articles in one interdisciplinary journal, Global Environmental Change (GEC). It is expected that they will diverge sufficiently to produce differences that are analogous to register differences. Instead of identifying these “registers” on external criteria, we use the dimensional profiles of individual texts to identify ‘constellations’ of texts sharing combinations of features. Six such constellations are derived, consisting of texts with commonalities in their approaches to research: the development of predictive models; quantitative research; discussions of theory and policy; and human-environment studies focusing on individual voices. The identification of these constellations could not have been achieved through an a priori categorisation of texts

A Systematic Review of Recall Regimen and Maintenance Regimen of Patients with Dental Restorations. Part 2: Implant-Borne Restorations

Purpose To evaluate the current scientific evidence on patient recall and maintenance of implant-supported restorations, to standardize patient care regimens and improve maintenance of oral health. An additional purpose was to examine areas of deficiency in the current scientific literature and provide recommendations for future studies. Materials and Methods An electronic search for articles in the English language literature from the past 10 years was performed independently by multiple investigators using a systematic search process. After application of predetermined inclusion and exclusion criteria, the final list of articles was reviewed to meet the objectives of this review. Results The initial electronic search resulted in 2816 titles. The systematic application of inclusion and exclusion criteria resulted in 14 articles that satisfied the study objectives. An additional 6 articles were added through a supplemental search process for a total of 20 studies. Of these, 11 were randomized controlled clinical trials, and 9 were observational studies. The majority of the studies (15 out of 20) were conducted in the past 5 years and most studies were conducted in Europe (15), followed by Asia (2), South America (1), the United States (1), and the Middle East (1). Results from the qualitative data on a combined 1088 patients indicated that outcome improvements in recall and maintenance regimen were related to (1) patient/treatment characteristic (type of prosthesis, type of prosthetic components, and type of restorative materials); (2) specific oral topical agents or oral hygiene aids (electric toothbrush, interdental brush, chlorhexidine, triclosan, water flossers) and (3) professional intervention (oral hygiene maintenance, and maintenance of the prosthesis). Conclusions There is minimal evidence related to recall regimens in patients with implant-borne removable and fixed restorations; however, a considerable body of evidence indicates that patients with implant-borne removable and fixed restorations require lifelong professional recall regimens to provide biological and mechanical maintenance, customized for each patient. Current evidence also demonstrates that the use of specific oral topical agents and oral hygiene aids can improve professional and at-home maintenance of implant-borne restorations. There is evidence to demonstrate differences in mechanical and biological maintenance needs due to differences in prosthetic materials and designs. Deficiencies in existing evidence compel the forethought of creating clinical practice guidelines for recall and maintenance of patients with implant-borne dental restorations

Innovation in patient-centered care: lessons from a qualitative study of innovative health care organizations in Washington State

Background Growing interest in the promise of patient-centered care has led to numerous health care innovations, including the patient-centered medical home, shared decision-making, and payment reforms. How best to vet and adopt innovations is an open question. Washington State has been a leader in health care reform and is a rich laboratory for patient-centered innovations. We sought to understand the process of patient-centered care innovation undertaken by innovative health care organizations – from strategic planning to goal selection to implementation to maintenance. Methods We conducted key-informant interviews with executives at five health plans, five provider organizations, and ten primary care clinics in Washington State. At least two readers of each interview transcript identified themes inductively; final themes were determined by consensus. Results Innovation in patient-centered care was a strategic objective chosen by nearly every organization in this study. However, other goals were paramount: cost containment, quality improvement, and organization survival. Organizations commonly perceived effective chronic disease management and integrated health information technology as key elements for successful patient-centered care innovation. Inertia, resource deficits, fee-for-service payment, and regulatory limits on scope of practice were cited as barriers to innovation, while organization leadership, human capital, and adaptive culture facilitated innovation. Conclusions Patient-centered care innovations reflected organizational perspectives: health plans emphasized cost-effectiveness while providers emphasized health care delivery processes. Health plans and providers shared many objectives, yet the two rarely collaborated to achieve them. The process of innovation is heavily dependent on organizational culture and leadership. Policymakers can improve the pace and quality of patient-centered innovation by setting targets and addressing conditions for innovation

Clinical Practice Guidelines for Recall and Maintenance of Patients with Tooth-Borne and Implant-Borne Dental Restorations

Purpose To provide guidelines for patient recall regimen, professional maintenance regimen, and at-home maintenance regimen for patients with tooth-borne and implant-borne removable and fixed restorations. Materials and Methods The American College of Prosthodontists (ACP) convened a scientific panel of experts appointed by the ACP, American Dental Association (ADA), Academy of General Dentistry (AGD), and American Dental Hygienists Association (ADHA) who critically evaluated and debated recently published findings from two systematic reviews on this topic. The major outcomes and consequences considered during formulation of the clinical practice guidelines (CPGs) were risk for failure of tooth- and implant-borne restorations. The panel conducted a round table discussion of the proposed guidelines, which were debated in detail. Feedback was used to supplement and refine the proposed guidelines, and consensus was attained. Results A set of CPGs was developed for tooth-borne restorations and implant-borne restorations. Each CPG comprised (1) patient recall, (2) professional maintenance, and (3) at-home maintenance. For tooth-borne restorations, the professional maintenance and at-home maintenance CPGs were subdivided for removable and fixed restorations. For implant-borne restorations, the professional maintenance CPGs were subdivided for removable and fixed restorations and further divided into biological maintenance and mechanical maintenance for each type of restoration. The at-home maintenance CPGs were subdivided for removable and fixed restorations. Conclusions The clinical practice guidelines presented in this document were initially developed using the two systematic reviews. Additional guidelines were developed using expert opinion and consensus, which included discussion of the best clinical practices, clinical feasibility, and risk-benefit ratio to the patient. To the authors’ knowledge, these are the first CPGs addressing patient recall regimen, professional maintenance regimen, and at-home maintenance regimen for patients with tooth-borne and implant-borne restorations. This document serves as a baseline with the expectation of future modifications when additional evidence becomes available

Astro2020 Science White Paper: Triggered High-Priority Observations of Dynamic Solar System Phenomena

Unexpected dynamic phenomena have surprised solar system observers in the past and have led to important discoveries about solar system workings. Observations at the initial stages of these events provide crucial information on the physical processes at work. We advocate for long-term/permanent programs on ground-based and space-based telescopes of all sizes - including Extremely Large Telescopes (ELTs) - to conduct observations of high-priority dynamic phenomena, based on a predefined set of triggering conditions. These programs will ensure that the best initial dataset of the triggering event are taken; separate additional observing programs will be required to study the temporal evolution of these phenomena. While not a comprehensive list, the following are notional examples of phenomena that are rare, that cannot be anticipated, and that provide high-impact advances to our understandings of planetary processes. Examples include: new cryovolcanic eruptions or plumes on ocean worlds; impacts on Jupiter, Saturn, Uranus, or Neptune; extreme eruptions on Io; convective superstorms on Saturn, Uranus, or Neptune; collisions within the asteroid belt or other small-body populations; discovery of an interstellar object passing through our solar system (e.g. 'Oumuamua); and responses of planetary atmospheres to major solar flares or coronal mass ejections.Comment: Astro2020 white pape

Adsorption models of hybridization and post-hybridisation behaviour on oligonucleotide microarrays

Analysis of data from an Affymetrix Latin Square spike-in experiment indicates that measured fluorescence intensities of features on an oligonucleotide microarray are related to spike-in RNA target concentrations via a hyperbolic response function, generally identified as a Langmuir adsorption isotherm. Furthermore the asymptotic signal at high spike-in concentrations is almost invariably lower for a mismatch feature than for its partner perfect match feature. We survey a number of theoretical adsorption models of hybridization at the microarray surface and find that in general they are unable to explain the differing saturation responses of perfect and mismatch features. On the other hand, we find that a simple and consistent explanation can be found in a model in which equilibrium hybridization followed by partial dissociation of duplexes during the post-hybridization washing phase.Comment: 26 pages, 6 figures, some rearrangement of sections and some additions. To appear in J.Phys.(condensed matter