Showing papers by "University of Virginia published in 2010"
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TL;DR: A new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format, which allows the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks.
Abstract: 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 webbased 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
18,858 citations
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01 Mar 201018,472 citations
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University of California, Los Angeles1, Jet Propulsion Laboratory2, California Institute of Technology3, University of Arizona4, University of Virginia5, University of California, Davis6, Lawrence Livermore National Laboratory7, Monterey Institute for Research in Astronomy8, Goddard Space Flight Center9, National Radio Astronomy Observatory10, University of California, Berkeley11, Wilmington University12, Advanced Technology Center13
TL;DR: The Wide-field Infrared Survey Explorer (WISE) is mapping the whole sky following its launch on 14 December 2009 and completed its first full coverage of the sky on July 17 as discussed by the authors.
Abstract: The all sky surveys done by the Palomar Observatory Schmidt, the European Southern Observatory Schmidt, and the United Kingdom Schmidt, the InfraRed Astronomical Satellite and the 2 Micron All Sky Survey have proven to be extremely useful tools for astronomy with value that lasts for decades. The Wide-field Infrared Survey Explorer is mapping the whole sky following its launch on 14 December 2009. WISE began surveying the sky on 14 Jan 2010 and completed its first full coverage of the sky on July 17. The survey will continue to cover the sky a second time until the cryogen is exhausted (anticipated in November 2010). WISE is achieving 5 sigma point source sensitivities better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic in bands centered at wavelengths of 3.4, 4.6, 12 and 22 micrometers. Sensitivity improves toward the ecliptic poles 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 22 micrometers, and the astrometric precision for high SNR sources is better than 0.15".
7,182 citations
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United Nations Environment Programme1, BirdLife International2, Zoological Society of London3, Statistics Netherlands4, University of North Carolina at Chapel Hill5, Old Dominion University6, Conservation International7, Food and Agriculture Organization8, University of Virginia9, Royal Society for the Protection of Birds10, University of Queensland11, University of Cambridge12, National Center for Atmospheric Research13, World Wide Fund for Nature14, South African National Parks15, UNESCO16, University of British Columbia17, Tata Institute of Fundamental Research18, The Nature Conservancy19, Patuxent Wildlife Research Center20, American Bird Conservancy21, Stellenbosch University22, International Union for Conservation of Nature and Natural Resources23
TL;DR: Most indicators of the state of biodiversity showed declines, with no significant recent reductions in rate, whereas indicators of pressures on biodiversity showed increases, indicating that the Convention on Biological Diversity’s 2010 targets have not been met.
Abstract: In 2002, world leaders committed, through the Convention on Biological Diversity, to achieve a significant reduction in the rate of biodiversity loss by 2010. We compiled 31 indicators to report on progress toward this target. Most indicators of the state of biodiversity (covering species' population trends, extinction risk, habitat extent and condition, and community composition) showed declines, with no significant recent reductions in rate, whereas indicators of pressures on biodiversity (including resource consumption, invasive alien species, nitrogen pollution, overexploitation, and climate change impacts) showed increases. Despite some local successes and increasing responses (including extent and biodiversity coverage of protected areas, sustainable forest management, policy responses to invasive alien species, and biodiversity-related aid), the rate of biodiversity loss does not appear to be slowing.
3,993 citations
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TL;DR: Radio timing observations of the binary millisecond pulsar J1614-2230 that show a strong Shapiro delay signature are presented and the pulsar mass is calculated to be (1.97 ± 0.04)M⊙, which rules out almost all currently proposed hyperon or boson condensate equations of state.
Abstract: Neutron stars comprise the densest form of matter known to exist in our Universe, but their composition and properties are uncertain. Measurements of their masses and radii can constrain theoretical predictions of their composition, but so far it has not been possible to rule out many predictions of 'exotic' non-nucleonic components. Here, radio timing observations of the binary millisecond pulsar J1614-2230 are presented, allowing almost all currently proposed hyperon or boson condensate equations of state to be ruled out.
3,338 citations
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TL;DR: The Flourishing Scale as mentioned in this paper is a summary measure of the respondent's self-perceived success in important areas such as relationships, self-esteem, purpose, and optimism.
Abstract: Measures of well-being were created to assess psychological flourishing and feelings—positive feelings, negative feelings, and the difference between the two. The scales were evaluated in a sample of 689 college students from six locations. The Flourishing Scale is a brief 8-item summary measure of the respondent’s self-perceived success in important areas such as relationships, self-esteem, purpose, and optimism. The scale provides a single psychological well-being score. The measure has good psychometric properties, and is strongly associated with other psychological well-being scales. The Scale of Positive and Negative Experience produces a score for positive feelings (6 items), a score for negative feelings (6 items), and the two can be combined to create a balance score. This 12-item brief scale has a number of desirable features compared to earlier measures of positive and negative emotions. In particular, the scale assesses with a few items a broad range of negative and positive experiences and feelings, not just those of a certain type, and is based on the amount of time the feelings were experienced during the past 4 weeks. The scale converges well with measures of emotions and affective well-being.
2,860 citations
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01 Apr 2010TL;DR: In this paper, the major uses and adaptations of stakeholder theory across a broad array of disciplines such as business ethics, corporate strategy, finance, accounting, management, and marketing are reviewed.
Abstract: For the last 30 years a growing number of scholars and practitioners have been experimenting with concepts and models that facilitate our understanding of the complexities of today’s business challenges. Among these, “stakeholder theory” or “stakeholder thinking” has emerged as a new narrative to understand and remedy three interconnected business problems—the problem of understanding how value is created and traded, the problem of connecting ethics and capitalism, and the problem of helping managers think about management such that the first two problems are addressed. In this article, we review the major uses and adaptations of stakeholder theory across a broad array of disciplines such as business ethics, corporate strategy, finance, accounting, management, and marketing. We also evaluate and suggest future directions in which research on stakeholder theory can continue to provide useful insights into the practice of sustainable and ethical value creation.
2,778 citations
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Radboud University Nijmegen1, University of York2, University of Virginia3, Environment Agency4, Netherlands Environmental Assessment Agency5, University of Brasília6, Woods Hole Research Center7, Energy Research Centre of the Netherlands8, United States Forest Service9, Marshall University10, Swedish University of Agricultural Sciences11, Wageningen University and Research Centre12
TL;DR: Ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase, in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas.
Abstract: Atmospheric nitrogen (N) deposition is a recognized threat to plant diversity in temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems, from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such as direct toxicity of nitrogen gases and aerosols, long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem- and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase, in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition, and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America, especially for the more sensitive ecosystem types, including several ecosystems of high conservation importance. The results of this assessment show that the vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe), and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted studies are required in low background areas, especially in the G200 ecoregions.
2,154 citations
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TL;DR: A rapid algorithm for relationship inference using high-throughput genotype data typical of GWAS that allows the presence of unknown population substructure and performs relationship inference on millions of pairs of individuals in a matter of minutes, dozens of times faster than the most efficient existing algorithm.
Abstract: Motivation: Genome-wide association studies (GWASs) have been widely used to map loci contributing to variation in complex traits and risk of diseases in humans. Accurate specification of familial relationships is crucial for family-based GWAS, as well as in population-based GWAS with unknown (or unrecognized) family structure. The family structure in a GWAS should be routinely investigated using the SNP data prior to the analysis of population structure or phenotype. Existing algorithms for relationship inference have a major weakness of estimating allele frequencies at each SNP from the entire sample, under a strong assumption of homogeneous population structure. This assumption is often untenable.
Results: Here, we present a rapid algorithm for relationship inference using high-throughput genotype data typical of GWAS that allows the presence of unknown population substructure. The relationship of any pair of individuals can be precisely inferred by robust estimation of their kinship coefficient, independent of sample composition or population structure (sample invariance). We present simulation experiments to demonstrate that the algorithm has sufficient power to provide reliable inference on millions of unrelated pairs and thousands of relative pairs (up to 3rd-degree relationships). Application of our robust algorithm to HapMap and GWAS datasets demonstrates that it performs properly even under extreme population stratification, while algorithms assuming a homogeneous population give systematically biased results. Our extremely efficient implementation performs relationship inference on millions of pairs of individuals in a matter of minutes, dozens of times faster than the most efficient existing algorithm known to us.
Availability: Our robust relationship inference algorithm is implemented in a freely available software package, KING, available for download at http://people.virginia.edu/~wc9c/KING.
Contact: wmchen@virginia.edu
Supplementary information:Supplementary data are available at Bioinformatics online.
2,147 citations
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Pierre-and-Marie-Curie University1, Yale University2, University of British Columbia3, Bristol-Myers Squibb4, University of California, Los Angeles5, University of Virginia6, French Institute of Health and Medical Research7, University College London8, University of California, San Diego9, McGill University10, Goethe University Frankfurt11, University of Kentucky12, Tohoku University13, Newcastle University14, University of Lille Nord de France15, University of Nice Sophia Antipolis16, Brown University17, NewYork–Presbyterian Hospital18, Maastricht University Medical Centre19, VU University Amsterdam20
TL;DR: This paper aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities.
Abstract: Alzheimer's disease (AD) is classically defined as a dual clinicopathological entity. The recent advances in use of reliable biomarkers of AD that provide in-vivo evidence of the disease has stimulated the development of new research criteria that reconceptualise the diagnosis around both a specific pattern of cognitive changes and structural/biological evidence of Alzheimer's pathology. This new diagnostic framework has stimulated debate about the definition of AD and related conditions. The potential for drugs to intercede in the pathogenic cascade of the disease adds some urgency to this debate. This paper by the International Working Group for New Research Criteria for the Diagnosis of AD aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities. The cornerstone of this lexicon is to consider AD solely as a clinical and symptomatic entity that encompasses both predementia and dementia phases.
1,776 citations
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TL;DR: Adhesion formation and disassembly drive the migration cycle by activating Rho GTPases, which in turn regulate actin polymerization and myosin II activity, and therefore adhesion dynamics.
Abstract: Cell migration affects all morphogenetic processes and contributes to numerous diseases, including cancer and cardiovascular disease. For most cells in most environments, movement begins with protrusion of the cell membrane followed by the formation of new adhesions at the cell front that link the actin cytoskeleton to the substratum, generation of traction forces that move the cell forwards and disassembly of adhesions at the cell rear. Adhesion formation and disassembly drive the migration cycle by activating Rho GTPases, which in turn regulate actin polymerization and myosin II activity, and therefore adhesion dynamics.
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13 Jun 2010
TL;DR: The design, construction and verification of cyber-physical systems pose a multitude of technical challenges that must be addressed by a cross-disciplinary community of researchers and educators.
Abstract: Cyber-physical systems (CPS) are physical and engineered systems whose operations are monitored, coordinated, controlled and integrated by a computing and communication core. Just as the internet transformed how humans interact with one another, cyber-physical systems will transform how we interact with the physical world around us. Many grand challenges await in the economically vital domains of transportation, health-care, manufacturing, agriculture, energy, defense, aerospace and buildings. The design, construction and verification of cyber-physical systems pose a multitude of technical challenges that must be addressed by a cross-disciplinary community of researchers and educators.
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University of Virginia1, University of Chicago2, University of Texas MD Anderson Cancer Center3, Thomas Jefferson University4, Wake Forest University5, University of Colorado Denver6, Stanford University7, Memorial Sloan Kettering Cancer Center8, Orlando Regional Medical Center9, University of Texas Southwestern Medical Center10, University of Toronto11, University of Rochester12, University of Utah13, Johns Hopkins University14, University of Wisconsin-Madison15, Vrije Universiteit Brussel16, Fox Chase Cancer Center17, Duke University18
TL;DR: The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality.
Abstract: Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.
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Stanford University1, Indiana University – Purdue University Indianapolis2, Emory University3, University of Oklahoma4, University of Kansas5, Cornell University6, Thomas Jefferson University7, Marshfield Clinic8, Veterans Health Administration9, University of California, Los Angeles10, St. Joseph's Hospital and Medical Center11, Rush University Medical Center12, University of Pennsylvania13, University of California, San Francisco14, University of Virginia15, Columbia University16, Harvard University17, Medtronic plc18
TL;DR: A multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy is reported.
Abstract: Summary
Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy
Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation
Results: One hundred ten participants were randomized Baseline monthly median seizure frequency was 195 In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0002) Unadjusted median declines at the end of the blinded phase were 145% in the control group and 404% in the stimulated group Complex partial and “most severe” seizures were significantly reduced by stimulation By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months Five deaths occurred and none were from implantation or stimulation No participant had symptomatic hemorrhage or brain infection Two participants had acute, transient stimulation-associated seizures Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events
Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures Benefit persisted for 2 years of study Complication rates were modest Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures
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University of Cincinnati1, Washington University in St. Louis2, Boston Children's Hospital3, University of Illinois at Chicago4, University of California, Los Angeles5, Stanford University6, University of British Columbia7, University of Washington8, Cornell University9, Tufts University10, Veterans Health Administration11, University of Toronto12, University of Virginia13, Johns Hopkins University14
TL;DR: These updated guidelines replace those previously published in 2002 and 2003 and add recommendations for managing intra-abdominal infection in children, particularly where such management differs from that of adults; for appendicitis in patients of all ages; and for necrotizing enterocolitis in neonates.
Abstract: Evidence-based guidelines for managing patients with intra-abdominal infection were prepared by an Expert Panel of the Surgical Infection Society and the Infectious Diseases Society of America. These updated guidelines replace those previously published in 2002 and 2003. The guidelines are intended for treating patients who either have these infections or may be at risk for them. New information, based on publications from the period 2003-2008, is incorporated into this guideline document. The panel has also added recommendations for managing intra-abdominal infection in children, particularly where such management differs from that of adults; for appendicitis in patients of all ages; and for necrotizing enterocolitis in neonates.
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TL;DR: Developing a calibrated biosensor that measures forces across specific proteins in cells with piconewton (pN) sensitivity reveals that FA stabilization under force requires both vinculin recruitment and force transmission, and that, surprisingly, these processes can be controlled independently.
Abstract: Mechanical forces are central to developmental, physiological and pathological processes. However, limited understanding of force transmission within sub-cellular structures is a major obstacle to unravelling molecular mechanisms. Here we describe the development of a calibrated biosensor that measures forces across specific proteins in cells with piconewton (pN) sensitivity, as demonstrated by single molecule fluorescence force spectroscopy. The method is applied to vinculin, a protein that connects integrins to actin filaments and whose recruitment to focal adhesions (FAs) is force-dependent. We show that tension across vinculin in stable FAs is approximately 2.5 pN and that vinculin recruitment to FAs and force transmission across vinculin are regulated separately. Highest tension across vinculin is associated with adhesion assembly and enlargement. Conversely, vinculin is under low force in disassembling or sliding FAs at the trailing edge of migrating cells. Furthermore, vinculin is required for stabilizing adhesions under force. Together, these data reveal that FA stabilization under force requires both vinculin recruitment and force transmission, and that, surprisingly, these processes can be controlled independently.
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TL;DR: The ASRA consensus statements represent the collective experience of recognized experts in the field of neuraxial anesthesia and anticoagulation and are based on case reports, clinical series, pharmacology, hematology, and risk factors for surgical bleeding.
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TL;DR: It is shown that miR-9, which is upregulated in breast cancer cells, directly targets CDH1, the E-cadherin-encoding messenger RNA, leading to increased cell motility and invasiveness, and a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasis
Abstract: β-catenin signalling, which contributes to upregulated expression of the gene encoding vascular endothelial growth factor (VEGF); this leads, in turn, to increased tumour angiogenesis. Overexpression of miR-9 in otherwise non-metastatic breast tumour cells enables these cells to form pulmonary micrometastases in mice. Conversely, inhibiting miR-9 by using a ‘miRNA sponge’ in highly malignant cells inhibits metastasis formation. Expression of miR-9 is activated by MYC and MYCN, both of which directly bind to the mir-9-3 locus. Significantly, in human cancers, miR-9 levels correlate with MYCN amplification, tumour grade and metastatic status. These findings uncover a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasis-suppressing protein E-cadherin. Metastases are responsible for more than 90% of cancer-related mortality. These secondary growths arise through a multistep process that begins when cancer cells within primary tumours break away from neighbouring cells and invade the basement membrane 1 . This local invasion may frequently be triggered by contextual signals that carcinoma cells receive from the nearby stroma, causing them to undergo an epithelial–mesenchymal transition (EMT) 2 . Subsequently, metastasizing cells enter the circulation either directly or through lymphatics. Size constraints in the microvasculature cause many of these cells to be arrested at distant sites, where they may extravasate and enter the foreign tissue parenchyma. There they may remain dormant or, with low efficiency, proliferate from occult micrometastases to form angiogenic, clinically detectable metastases. The absence of EMT-inducing signals in the foreign microenvironment may cause such disseminated cells to revert to an epithelial phenotype by means of a mesenchymal–epithelial transition. Critical regulators of the metastatic process include both proteins and miRNAs 3,4
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TL;DR: The importance of ECM as a dynamic repository for growth factors is highlighted along with more recent studies implicating the 3-dimensional organization and physical properties of theECM as it relates to cell signaling and the regulation of morphogenetic cell behaviors.
01 Feb 2010
TL;DR: In this article, the authors uncover a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasissuppressing protein E-cadherin.
Abstract: β-catenin signalling, which contributes to upregulated expression of the gene encoding vascular endothelial growth factor (VEGF); this leads, in turn, to increased tumour angiogenesis. Overexpression of miR-9 in otherwise non-metastatic breast tumour cells enables these cells to form pulmonary micrometastases in mice. Conversely, inhibiting miR-9 by using a ‘miRNA sponge’ in highly malignant cells inhibits metastasis formation. Expression of miR-9 is activated by MYC and MYCN, both of which directly bind to the mir-9-3 locus. Significantly, in human cancers, miR-9 levels correlate with MYCN amplification, tumour grade and metastatic status. These findings uncover a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasis-suppressing protein E-cadherin. Metastases are responsible for more than 90% of cancer-related mortality. These secondary growths arise through a multistep process that begins when cancer cells within primary tumours break away from neighbouring cells and invade the basement membrane 1 . This local invasion may frequently be triggered by contextual signals that carcinoma cells receive from the nearby stroma, causing them to undergo an epithelial–mesenchymal transition (EMT) 2 . Subsequently, metastasizing cells enter the circulation either directly or through lymphatics. Size constraints in the microvasculature cause many of these cells to be arrested at distant sites, where they may extravasate and enter the foreign tissue parenchyma. There they may remain dormant or, with low efficiency, proliferate from occult micrometastases to form angiogenic, clinically detectable metastases. The absence of EMT-inducing signals in the foreign microenvironment may cause such disseminated cells to revert to an epithelial phenotype by means of a mesenchymal–epithelial transition. Critical regulators of the metastatic process include both proteins and miRNAs 3,4
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TL;DR: In this article, the authors propose four components of a customer's engagement value (CEV) with a firm: customer lifetime value (the customer's purchase behavior), customer referral value (as it relates to incentivized referral of new customers), customer influencer value (which includes the customer's behavior to influence other customers, that is increasing acquisition, retention, and share of wallet through word of mouth of existing customers as well as prospects).
Abstract: Customers can interact with and create value for firms in a variety of ways. This article proposes that assessing the value of customers based solely upon their transactions with a firm may not be sufficient, and valuing this engagement correctly is crucial in avoiding undervaluation and overvaluation of customers. We propose four components of a customer's engagement value (CEV) with a firm. The first component is customer lifetime value (the customer's purchase behavior), the second is customer referral value (as it relates to incentivized referral of new customers), the third is customer influencer value (which includes the customer's behavior to influence other customers, that is increasing acquisition, retention, and share of wallet through word of mouth of existing customers as well as prospects), and the fourth is customer knowledge value (the value added to the firm by feedback from the customer). CEV provides a comprehensive framework that can ultimately lead to more efficient marketing strategies that enable higher long-term contribution from the customer. Metrics to measure CEV, future research propositions regarding relationships between the four components of CEV are proposed and marketing strategies that can leverage these relationships suggested.
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University of North Carolina at Chapel Hill1, University of Texas Health Science Center at Houston2, University of Pavia3, University of Cambridge4, University of Milan5, Stanford University6, Kaiser Permanente7, National Institutes of Health8, University of Washington9, Wake Forest University10, Cedars-Sinai Medical Center11, Group Health Cooperative12, Lund University13, University of Michigan14, National Institute for Health and Welfare15, University of Helsinki16, Boston University17, University of Chicago18, International Agency for Research on Cancer19, Charles University in Prague20, French Institute of Health and Medical Research21, Institut Gustave Roussy22, University of Padua23, University of Glasgow24, Palacký University, Olomouc25, Trinity College, Dublin26, National and Kapodistrian University of Athens27, Newcastle University28, University of Aberdeen29, University of Turin30, Nofer Institute of Occupational Medicine31, Russian Academy32, University of Exeter33, Harvard University34, Massachusetts Institute of Technology35, Broad Institute36, VU University Amsterdam37, Erasmus University Rotterdam38, University of Virginia39, Virginia Commonwealth University40, University of Pennsylvania41, Duke University42, University of Ioannina43, Tufts University44
TL;DR: A meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium found the strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3, and three loci associated with number of cigarettes smoked per day were identified.
Abstract: Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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TL;DR: The impacts associated with algae production were determined using a stochastic life cycle model and compared with switchgrass, canola, and corn farming, and it is indicated that these conventional crops have lower environmental impacts than algae in energy use, greenhouse gas emissions, and water regardless of cultivation location.
Abstract: Algae are an attractive source of biomass energy since they do not compete with food crops and have higher energy yields per area than terrestrial crops. In spite of these advantages, algae cultivation has not yet been compared with conventional crops from a life cycle perspective. In this work, the impacts associated with algae production were determined using a stochastic life cycle model and compared with switchgrass, canola, and corn farming. The results indicate that these conventional crops have lower environmental impacts than algae in energy use, greenhouse gas emissions, and water regardless of cultivation location. Only in total land use and eutrophication potential do algae perform favorably. The large environmental footprint of algae cultivation is driven predominantly by upstream impacts, such as the demand for CO2 and fertilizer. To reduce these impacts, flue gas and, to a greater extent, wastewater could be used to offset most of the environmental burdens associated with algae. To demonstra...
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TL;DR: In this article, the authors discuss the emerging research concerned with sustainable development and entrepreneurship, which is the focus of this special issue of the Journal of Business Venturing (JBEV).
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TL;DR: PANX1 is identified as a plasma membrane channel mediating the regulated release of find-me signals and selective plasma membrane permeability during apoptosis, and a new mechanism of PANX1 activation by caspases is identified.
Abstract: Apoptotic cells were shown recently to discharge the nucleotides ATP and UTP to act as 'find-me' signals for phagocytes that engulf dying cells before they release potentially harmful cellular contents. This paper shows that the release of ATP and UTP is through the plasma membrane channel pannexin 1, which is specifically opened by caspase activity. The discovery of a role for pannexin 1 in phagocyte chemoattraction could have implications for human diseases that arise from defective clearance of dying cells. Apoptotic cells discharge ATP and UTP, which act as 'find-me' signals for phagocytes that in turn engulf dying cells before potentially harmful cellular contents are released. These authors show that the release of ATP and UTP is exclusively by means of the plasma membrane channel pannexin 1, which is opened specifically by caspase activity. Apoptotic cells release ‘find-me’ signals at the earliest stages of death to recruit phagocytes1. The nucleotides ATP and UTP represent one class of find-me signals2, but their mechanism of release is not known. Here, we identify the plasma membrane channel pannexin 1 (PANX1) as a mediator of find-me signal/nucleotide release from apoptotic cells. Pharmacological inhibition and siRNA-mediated knockdown of PANX1 led to decreased nucleotide release and monocyte recruitment by apoptotic cells. Conversely, PANX1 overexpression enhanced nucleotide release from apoptotic cells and phagocyte recruitment. Patch-clamp recordings showed that PANX1 was basally inactive, and that induction of PANX1 currents occurred only during apoptosis. Mechanistically, PANX1 itself was a target of effector caspases (caspases 3 and 7), and a specific caspase-cleavage site within PANX1 was essential for PANX1 function during apoptosis. Expression of truncated PANX1 (at the putative caspase cleavage site) resulted in a constitutively open channel. PANX1 was also important for the ‘selective’ plasma membrane permeability of early apoptotic cells to specific dyes3. Collectively, these data identify PANX1 as a plasma membrane channel mediating the regulated release of find-me signals and selective plasma membrane permeability during apoptosis, and a new mechanism of PANX1 activation by caspases.
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TL;DR: This review focuses on recent literature that describes how CNT-based electrochemical sensors are being developed to detect neurotransmitters, proteins, small molecules such as glucose, and DNA.
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University of British Columbia1, Allen Institute for Brain Science2, Memorial Sloan Kettering Cancer Center3, University of Virginia4, University of California, San Francisco5, Thomas Jefferson University6, University of Toronto7, University of Utah8, University of Minnesota9, Mayo Clinic10, Northwestern University11, University of Pittsburgh12, Johns Hopkins University13, Harvard University14, Ohio State University15, University of Texas Health Science Center at Houston16, University of Texas MD Anderson Cancer Center17, Icahn School of Medicine at Mount Sinai18, Kanazawa University19, Pontifícia Universidade Católica do Paraná20, University of South Florida21, University of Saskatchewan22
TL;DR: The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation and aid surgeons in assessing the key components of spinal instability due to neoplasia.
Abstract: Study design Systematic review and modified Delphi technique. Objective To use an evidence-based medicine process using the best available literature and expert opinion consensus to develop a comprehensive classification system to diagnose neoplastic spinal instability. Summary of background data Spinal instability is poorly defined in the literature and presently there is a lack of guidelines available to aid in defining the degree of spinal instability in the setting of neoplastic spinal disease. The concept of spinal instability remains important in the clinical decision-making process for patients with spine tumors. Methods We have integrated the evidence provided by systematic reviews through a modified Delphi technique to generate a consensus of best evidence and expert opinion to develop a classification system to define neoplastic spinal instability. Results A comprehensive classification system based on patient symptoms and radiographic criteria of the spine was developed to aid in predicting spine stability of neoplastic lesions. The classification system includes global spinal location of the tumor, type and presence of pain, bone lesion quality, spinal alignment, extent of vertebral body collapse, and posterolateral spinal element involvement. Qualitative scores were assigned based on relative importance of particular factors gleaned from the literature and refined by expert consensus. Conclusion The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation. It can also aid surgeons in assessing the key components of spinal instability due to neoplasia and may become a prognostic tool for surgical decision-making when put in context with other key elements such as neurologic symptoms, extent of disease, prognosis, patient health factors, oncologic subtype, and radiosensitivity of the tumor.
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TL;DR: Study of the mechanism of ethanol and glycerol oxidation to acids over various supported gold and platinum catalysts finds that oxygen atoms originating from hydroxide ions instead of molecular oxygen are incorporated into the alcohol during the oxidation reaction.
Abstract: The selective oxidation of alcohols in aqueous phase over supported metal catalysts is facilitated by high-pH conditions. We have studied the mechanism of ethanol and glycerol oxidation to acids over various supported gold and platinum catalysts. Labeling experiments with (18)O(2) and H(2)(18)O demonstrate that oxygen atoms originating from hydroxide ions instead of molecular oxygen are incorporated into the alcohol during the oxidation reaction. Density functional theory calculations suggest that the reaction path involves both solution-mediated and metal-catalyzed elementary steps. Molecular oxygen is proposed to participate in the catalytic cycle not by dissociation to atomic oxygen but by regenerating hydroxide ions formed via the catalytic decomposition of a peroxide intermediate.
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University of Virginia1, Thomas Jefferson University2, Fred Hutchinson Cancer Research Center3, University of Texas Health Science Center at San Antonio4, Harvard University5, University of Texas MD Anderson Cancer Center6, American Cancer Society7, Emory University8, University of Lausanne9, University of Geneva10
TL;DR: It is recommended that asymptomatic men who have at least a 10‐year life expectancy have an opportunity to make an informed decision with their health care provider about screening for prostate cancer after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening.
Abstract: In 2009, the American Cancer Society (ACS) Prostate Cancer Advisory Committee began the process of a complete update of recommendations for early prostate cancer detection. A series of systematic evidence reviews was conducted focusing on evidence related to the early detection of prostate cancer, test performance, harms of therapy for localized prostate cancer, and shared and informed decision making in prostate cancer screening. The results of the systematic reviews were evaluated by the ACS Prostate Cancer Advisory Committee, and deliberations about the evidence occurred at committee meetings and during conference calls. On the basis of the evidence and a consensus process, the Prostate Cancer Advisory Committee developed the guideline, and a writing committee drafted a guideline document that was circulated to the entire committee for review and revision. The document was then circulated to peer reviewers for feedback, and finally to the ACS Mission Outcomes Committee and the ACS Board of Directors for approval. The ACS recommends that asymptomatic men who have at least a 10-year life expectancy have an opportunity to make an informed decision with their health care provider about screening for prostate cancer after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. Prostate cancer screening should not occur without an informed decision-making process. Men at average risk should receive this information beginning at age 50 years. Men in higher risk groups should receive this information before age 50 years. Men should either receive this information directly from their health care providers or be referred to reliable and culturally appropriate sources. Patient decision aids are helpful in preparing men to make a decision whether to be tested.
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TL;DR: Questions related to age, how many distinct influences are contributing to the relations between age and cognitive functioning, do the differences between people increase with advancing age, and what is responsible for the discrepancies between cross-sectional and longitudinal age comparisons of cognitive functioning are reviewed.
Abstract: Research concerned with relations between adult age and cognitive functioning is briefly reviewed. The coverage is necessarily selective, and is organized in terms of five major questions. These are what abilities are related to age, how many distinct influences are contributing to the relations between age and cognitive functioning, do the differences between people increase with advancing age, what is responsible for the discrepancies between cross-sectional and longitudinal age comparisons of cognitive functioning, and what methods can be used to identify causes of age-related influences on cognition. Although definitive answers are not yet possible, quite a bit of information relevant to the questions is now available. Moreover, the existing information has implications for the design, analysis, and interpretation of cognitive and neuropsychological research concerned with aging.