University of Virginia

Information technology (IT) acceptance research has yielded many competing models, each with different sets of acceptance determinants. In this paper, we (1) review user acceptance literature and discuss eight prominent models, (2) empirically compare the eight models and their extensions, (3) formulate a unified model that integrates elements across the eight models, and (4) empirically validate the unified model. The eight models reviewed are the theory of reasoned action, the technology acceptance model, the motivational model, the theory of planned behavior, a model combining the technology acceptance model and the theory of planned behavior, the model of PC utilization, the innovation diffusion theory, and the social cognitive theory. Using data from four organizations over a six-month period with three points of measurement, the eight models explained between 17 percent and 53 percent of the variance in user intentions to use information technology. Next, a unified model, called the Unified Theory of Acceptance and Use of Technology (UTAUT), was formulated, with four core determinants of intention and usage, and up to four moderators of key relationships. UTAUT was then tested using the original data and found to outperform the eight individual models (adjusted R2 of 69 percent). UTAUT was then confirmed with data from two new organizations with similar results (adjusted R2 of 70 percent). UTAUT thus provides a useful tool for managers needing to assess the likelihood of success for new technology introductions and helps them understand the drivers of acceptance in order to proactively design interventions (including training, marketing, etc.) targeted at populations of users that may be less inclined to adopt and use new systems. The paper also makes several recommendations for future research including developing a deeper understanding of the dynamic influences studied here, refining measurement of the core constructs used in UTAUT, and understanding the organizational outcomes associated with new technology use.

MOTIVATION: Testing for correlations between different sets of genomic features is a fundamental task in genomics research. However, searching for overlaps between features with existing web-based methods is complicated by the massive datasets that are routinely produced with current sequencing technologies. Fast and flexible tools are therefore required to ask complex questions of these data in an efficient manner. RESULTS: This article introduces a new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format. BEDTools also supports the comparison of sequence alignments in BAM format to both BED and GFF features. The tools are extremely efficient and allow the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks. BEDTools can be combined with one another as well as with standard UNIX commands, thus facilitating routine genomics tasks as well as pipelines that can quickly answer intricate questions of large genomic datasets. AVAILABILITY AND IMPLEMENTATION: BEDTools was written in C++. Source code and a comprehensive user manual are freely available at http://code.google.com/p/bedtools CONTACT: aaronquinlan@gmail.com; imh4y@virginia.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Strategic Management: A Stakeholder Approach was first published in 1984 as a part of the Pitman series in Business and Public Policy. Its publication proved to be a landmark moment in the development of stakeholder theory. Widely acknowledged as a world leader in business ethics and strategic management, R. Edward Freeman's foundational work continues to inspire scholars and students concerned with a more practical view of how business and capitalism actually work. Business can be understood as a system of how we create value for stakeholders. This worldview connects business and capitalism with ethics once and for all. On the 25th anniversary of publication, Cambridge University Press are delighted to be able to offer a new print-on-demand edition of his work to a new generation of readers

Part I: Introduction 1. Theoretical Background Part II: Method 2. Procedures 3. Measures and Methods of Assessment Part III: Results 4. Descriptive Account of Behavior in Each Episode 5. Normative Trends across Episodes 6. An Examination of the Classificatory System: A Multiple Discriminate Function Analysis 7. Relationships between Infant Behavior in the Strange Situation and at Home 8. Relationships between Infant Behavior in the Strange Situation and Maternal Behavior at Home 9. A Review of Strange-Situation Studies of One-Year-Olds 10. A Review of Strange-Situation Studies of Two- to Four-Year-Olds 11. The Effects of Repetition of the Strange Situation 12. Subgroups and Their Usefulness Part IV: Discussion 13. Discussion of Normative Issues 14. Individual Differences: In Light of Contrasting Paradigms 15. An Interpretation of Individual Differences Appendix I: Instructions to Mother Appendix II: Instructions for Coding and Tabulating Frequency of Behaviors Appendix III: Scoring System for Interactive Behaviors Appendix IV: Maternal Caregiving and Interaction Scales Appendix V: Secure Base Behavior At Home Appendix VI: Supplementary Statistical Findings

Between 1997 June and 2001 February the Two Micron All Sky Survey (2MASS) collected 25.4 Tbytes of raw imaging data covering 99.998% of the celestial sphere in the near-infrared J (1.25 μm), H (1.65 μm), and Ks (2.16 μm) bandpasses. Observations were conducted from two dedicated 1.3 m diameter telescopes located at Mount Hopkins, Arizona, and Cerro Tololo, Chile. The 7.8 s of integration time accumulated for each point on the sky and strict quality control yielded a 10 σ point-source detection level of better than 15.8, 15.1, and 14.3 mag at the J, H, and Ks bands, respectively, for virtually the entire sky. Bright source extractions have 1 σ photometric uncertainty of <0.03 mag and astrometric accuracy of order 100 mas. Calibration offsets between any two points in the sky are <0.02 mag. The 2MASS All-Sky Data Release includes 4.1 million compressed FITS images covering the entire sky, 471 million source extractions in a Point Source Catalog, and 1.6 million objects identified as extended in an Extended Source Catalog.

We have developed three computer programs for comparisons of protein and DNA sequences. They can be used to search sequence data bases, evaluate similarity scores, and identify periodic structures based on local sequence similarity. The FASTA program is a more sensitive derivative of the FASTP program, which can be used to search protein or DNA sequence data bases and can compare a protein sequence to a DNA sequence data base by translating the DNA data base as it is searched. FASTA includes an additional step in the calculation of the initial pairwise similarity score that allows multiple regions of similarity to be joined to increase the score of related sequences. The RDF2 program can be used to evaluate the significance of similarity scores using a shuffling method that preserves local sequence composition. The LFASTA program can display all the regions of local similarity between two sequences with scores greater than a threshold, using the same scoring parameters and a similar alignment algorithm; these local similarities can be displayed as a "graphic matrix" plot or as individual alignments. In addition, these programs have been generalized to allow comparison of DNA or protein sequences based on a variety of alternative scoring matrices.

To date, the phenomenon of entrepreneurship has lacked a conceptual framework. In this note we draw upon previous research conducted in the different social science disciplines and applied fields of business to create a conceptual framework for the field. With this framework we explain a set of empirical phenomena and predict a set of outcomes not explained or predicted by conceptual frameworks already in existence in other fields.

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings.

Chromatin, the physiological template of all eukaryotic genetic information, is subject to a diverse array of posttranslational modifications that largely impinge on histone amino termini, thereby regulating access to the underlying DNA. Distinct histone amino-terminal modifications can generate synergistic or antagonistic interaction affinities for chromatin-associated proteins, which in turn dictate dynamic transitions between transcriptionally active or transcriptionally silent chromatin states. The combinatorial nature of histone amino-terminal modifications thus reveals a "histone code" that considerably extends the information potential of the genetic code. We propose that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.

Many of the complex problems faced by decision makers involve multiple conflicting objectives. This book describes how a confused decision maker, who wishes to make a reasonable and responsible choice among alternatives, can systematically probe his true feelings in order to make those critically important, vexing trade-offs between incommensurable objectives. The theory is illustrated by many real concrete examples taken from a host of disciplinary settings. The standard approach in decision theory or decision analysis specifies a simplified single objective like monetary return to maximise. By generalising from the single objective case to the multiple objective case, this book considerably widens the range of applicability of decision analysis.

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother–father–child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research. This issue of Nature contains the first publication from The 1000 Genomes Project, an international collaboration that will produce an extensive public catalogue of human genetic variation. The plan, in fact, is to sequence about 2,000 unidentified individuals from 20 populations around the world. This first paper presents the results from the project's pilot phase, testing three different strategies for genome-wide sequencing with high-throughput platforms: low-coverage whole-genome sequencing of 179 individuals in three population groups, high-coverage sequencing of two mother–father–child trios, and exon-targeted sequencing of 697 individuals from seven populations. The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

The all sky surveys done by the Palomar Observatory Schmidt, the European Southern Observatory Schmidt, and
\nthe United Kingdom Schmidt, the InfraRed Astronomical Satellite, and the Two Micron All Sky Survey have
\nproven to be extremely useful tools for astronomy with value that lasts for decades. The Wide-field Infrared
\nSurvey Explorer (WISE) is mapping the whole sky following its launch on 2009 December 14. WISE began
\nsurveying the sky on 2010 January 14 and completed its first full coverage of the sky on July 17. The survey
\nwill continue to cover the sky a second time until the cryogen is exhausted (anticipated in 2010 November).
\nWISE is achieving 5σ point source sensitivities better than 0.08, 0.11, 1, and 6 mJy in unconfused regions on
\nthe ecliptic in bands centered at wavelengths of 3.4, 4.6, 12, and 22μm. Sensitivity improves toward the ecliptic
\npoles due to denser coverage and lower zodiacal background. The angular resolution is 6".1, 6".4, 6".5, and 12".0 at 3.4, 4.6, 12, and 22μm, and the astrometric precision for high signal-to-noise sources is better than 0".15.
\n

Research on moral judgment has been dominated by rationalist models, in which moral judgment is thought to be caused by moral reasoning. The author gives 4 reasons for considering the hypothesis that moral reasoning does not cause moral judgment; rather, moral reasoning is usually a post hoc construction, generated after a judgment has been reached. The social intuitionist model is presented as an alternative to rationalist models. The model is a social model in that it deemphasizes the private reasoning done by individuals and emphasizes instead the importance of social and cultural influences. The model is an intuitionist model in that it states that moral judgment is generally the result of quick, automatic evaluations (intuitions). The model is more consistent that rationalist models with recent findings in social, cultural, evolutionary, and biological psychology, as well as in anthropology and primatology.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

Entropy, as it relates to dynamical systems, is the rate of information production. Methods for estimation of the entropy of a system represented by a time series are not, however, well suited to analysis of the short and noisy data sets encountered in cardiovascular and other biological studies. Pincus introduced approximate entropy (ApEn), a set of measures of system complexity closely related to entropy, which is easily applied to clinical cardiovascular and other time series. ApEn statistics, however, lead to inconsistent results. We have developed a new and related complexity measure, sample entropy (SampEn), and have compared ApEn and SampEn by using them to analyze sets of random numbers with known probabilistic character. We have also evaluated cross-ApEn and cross-SampEn, which use cardiovascular data sets to measure the similarity of two distinct time series. SampEn agreed with theory much more closely than ApEn over a broad range of conditions. The improved accuracy of SampEn statistics should make them useful in the study of experimental clinical cardiovascular and other biological time series.

MOTIVATION: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. RESULTS: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. AVAILABILITY: GROMACS is an open source and free software available from http://www.gromacs.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 2,873 new measurements from 758 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. Particle properties and search limits are listed in Summary Tables. We give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 118 reviews are many that are new or heavily revised, including a new review on Neutrinos in Cosmology.Starting with this edition, the Review is divided into two volumes. Volume 1 includes the Summary Tables and all review articles. Volume 2 consists of the Particle Listings. Review articles that were previously part of the Listings are now included in volume 1.The complete Review (both volumes) is published online on the website of the Particle Data Group (http://pdg.lbl.gov) and in a journal. Volume 1 is available in print as the PDG Book. A Particle Physics Booklet with the Summary Tables and essential tables, figures, and equations from selected review articles is also available.The 2018 edition of the Review of Particle Physics should be cited as: M. Tanabashi et al. (Particle Data Group), Phys. Rev. D 98, 030001 (2018).

Humans continue to transform the global nitrogen cycle at a record pace, reflecting an increased combustion of fossil fuels, growing demand for nitrogen in agriculture and industry, and pervasive inefficiencies in its use. Much anthropogenic nitrogen is lost to air, water, and land to cause a cascade of environmental and human health problems. Simultaneously, food production in some parts of the world is nitrogen-deficient, highlighting inequities in the distribution of nitrogen-containing fertilizers. Optimizing the need for a key human resource while minimizing its negative consequences requires an integrated interdisciplinary approach and the development of strategies to decrease nitrogen-containing waste.

In this 1989 book Rorty argues that thinkers such as Nietzsche, Freud, and Wittgenstein have enabled societies to see themselves as historical contingencies, rather than as expressions of underlying, ahistorical human nature or as realizations of suprahistorical goals. This ironic perspective on the human condition is valuable on a private level, although it cannot advance the social or political goals of liberalism. In fact Rorty believes that it is literature not philosophy that can do this, by promoting a genuine sense of human solidarity. A truly liberal culture, acutely aware of its own historical contingency, would fuse the private, individual freedom of the ironic, philosophical perspective with the public project of human solidarity as it is engendered through the insights and sensibilities of great writers. The book has a characteristically wide range of reference from philosophy through social theory to literary criticism. It confirms Rorty's status as a uniquely subtle theorist, whose writing will prove absorbing to academic and nonacademic readers alike.