Showing papers by "Indiana University published in 2011"
TL;DR: This work investigates whether measurements of collective mood states derived from large-scale Twitter feeds are correlated to the value of the Dow Jones Industrial Average (DJIA) over time and indicates that the accuracy of DJIA predictions can be significantly improved by the inclusion of specific public mood dimensions but not others.
4,453 citations
01 Jan 2011
TL;DR: Overweight or obesity in adolescents has reache epidemic proportions in the USA and other industr alized countries and these conditions, although lumped together in research and in commentarie reflect adolescents’ being toward the heavier point a continuum that would range from underweight morbidly obese.
Abstract: e w id r as e, se er t st al h r Overweight or obesity in adolescents has reache epidemic proportions in the USA and other industr alized countries. These conditions, although ofte lumped together in research and in commentarie reflect adolescents’ being toward the heavier point a continuum that would range from underweight morbidly obese. The terms may be used interchang ably, but there is no doubt that, in the US a considerable percentage of adolescents suffer fro too much body fat. The prevalence of obesity (bod mass index [BMI] >95th percentile) among adole cents aged 12–19 years is now one in six (17.6%); an one in three (34.9%) US adolescents are overweight obese (BMI>85th percentile) (Story et al. 2009). Oth industrialized countries, such as Canada, Japa Germany, and China also are beginning to experien increasing problems related to obesity (Cornette 2008 Being on the overweight side of the weight continuu means being afflicted with a serious, chronic disea that can cause substantial harm to adolescents’ curre and future health. Although terms may be used loosely, individua only are formally deemed obese by physicians. The are some rules of thumb and formulas that often a used, especially in social science studies, but physician diagnose whether adolescents are obese. Discussion measurements tends to focus on that diagnos A diagnosis of obesity typically involves using a bod mass index (BMI). BMI is a measure of weight propo tionate to height, which is deemed a useful measure the amount of body fat. Although there are other mo precise ways to measure excess fat, experts now recom mend using BMI because it is easily obtained, strong
2,963 citations
TL;DR: It is argued that there are two broad types of support, emotional sustenance and active coping assistance, and two broad categories of supporters, significant others and experientially similar others, who specialize in supplying different types ofSupport to distressed individuals.
Abstract: Over the past 30 years investigators have called repeatedly for research on the mechanisms through which social relationships and social support improve physical and psychological well-being, both directly and as stress buffers. I describe seven possible mechanisms: social influence/social comparison, social control, role-based purpose and meaning (mattering), self-esteem, sense of control, belonging and companionship, and perceived support availability. Stress-buffering processes also involve these mechanisms. I argue that there are two broad types of support, emotional sustenance and active coping assistance, and two broad categories of supporters, significant others and experientially similar others, who specialize in supplying different types of support to distressed individuals. Emotionally sustaining behaviors and instrumental aid from significant others and empathy, active coping assistance, and role modeling from similar others should be most efficacious in alleviating the physical and emotional impacts of stressors.
2,510 citations
TL;DR: It is demonstrated that brain hubs form a so-called “rich club,” characterized by a tendency for high-degree nodes to be more densely connected among themselves than nodes of a lower degree, providing important information on the higher-level topology of the brain network.
Abstract: The human brain is a complex network of interlinked regions. Recent studies have demonstrated the existence of a number of highly connected and highly central neocortical hub regions, regions that play a key role in global information integration between different parts of the network. The potential functional importance of these “brain hubs” is underscored by recent studies showing that disturbances of their structural and functional connectivity profile are linked to neuropathology. This study aims to map out both the subcortical and neocortical hubs of the brain and examine their mutual relationship, particularly their structural linkages. Here, we demonstrate that brain hubs form a so-called “rich club,” characterized by a tendency for high-degree nodes to be more densely connected among themselves than nodes of a lower degree, providing important information on the higher-level topology of the brain network. Whole-brain structural networks of 21 subjects were reconstructed using diffusion tensor imaging data. Examining the connectivity profile of these networks revealed a group of 12 strongly interconnected bihemispheric hub regions, comprising the precuneus, superior frontal and superior parietal cortex, as well as the subcortical hippocampus, putamen, and thalamus. Importantly, these hub regions were found to be more densely interconnected than would be expected based solely on their degree, together forming a rich club. We discuss the potential functional implications of the rich-club organization of the human connectome, particularly in light of its role in information integration and in conferring robustness to its structural core.
2,089 citations
Posted Content•
TL;DR: New and existing techniques are integrated into a comprehensive set of recommendations that can be used to give researchers in MIS and the behavioral sciences a framework for developing valid measures.
Abstract: Despite the fact that validating the measures of constructs is critical to building cumulative knowledge in MIS and the behavioral sciences, the process of scale development and validation continues to be a challenging activity. Undoubtedly, part of the problem is that many of the scale development procedures advocated in the literature are limited by the fact that they: (a) fail to adequately discuss how to develop appropriate conceptual definitions of the focal construct; (b) often fail to properly specify the measurement model that relates the latent construct to its indicators; and (c) underutilize techniques that provide evidence that the set of items used to represent the focal construct actually measures what it purports to measure. Therefore, the purpose of the present paper is to integrate new and existing techniques into a comprehensive set of recommendations that can be used to give researchers in MIS and the behavioral sciences a framework for developing valid measures. First, we briefly elaborate upon some of the limitations of current scale development practices. Following this, we discuss each of the steps in the scale development process while paying particular attention to the differences that are required when one is attempting to develop scales for constructs with formative indicators as opposed to constructs with reflective indicators. Finally, we discuss several things that should be done after the initial development of a scale to examine its generalizability and to enhance its usefulness.
1,966 citations
TL;DR: In this article, a comprehensive set of recommendations that can be used to give researchers in MIS and the behavioral sciences a framework for developing valid measures is presented. But the scale development and validation of constructs is still a challenging activity.
Abstract: Despite the fact that validating the measures of constructs is critical to building cumulative knowledge in MIS and the behavioral sciences, the process of scale development and validation continues to be a challenging activity Undoubtedly, part of the problem is that many of the scale development procedures advocated in the literature are limited by the fact that they (1) fail to adequately discuss how to develop appropriate conceptual definitions of the focal construct, (2) often fail to properly specify the measurement model that relates the latent construct to its indicators, and (3) underutilize techniques that provide evidence that the set of items used to represent the focal construct actually measures what it purports to measure Therefore, the purpose of the present paper is to integrate new and existing techniques into a comprehensive set of recommendations that can be used to give researchers in MIS and the behavioral sciences a framework for developing valid measures First, we briefly elaborate upon some of the limitations of current scale development practices Following this, we discuss each of the steps in the scale development process while paying particular attention to the differences that are required when one is attempting to develop scales for constructs with formative indicators as opposed to constructs with reflective indicators Finally, we discuss several things that should be done after the initial development of a scale to examine its generalizability and to enhance its usefulness
1,783 citations
TL;DR: A guide to analyzing colocalization in cell biology studies is provided, emphasizing practical application of quantitative tools that are now widely available in commercial and free image analysis software.
Abstract: Fluorescence microscopy is one of the most powerful tools for elucidating the cellular functions of proteins and other molecules. In many cases, the function of a molecule can be inferred from its association with specific intracellular compartments or molecular complexes, which is typically determined by comparing the distribution of a fluorescently labeled version of the molecule with that of a second, complementarily labeled probe. Although arguably the most common application of fluorescence microscopy in biomedical research, studies evaluating the "colocalization" of two probes are seldom quantified, despite a diversity of image analysis tools that have been specifically developed for that purpose. Here we provide a guide to analyzing colocalization in cell biology studies, emphasizing practical application of quantitative tools that are now widely available in commercial and free image analysis software.
1,560 citations
University of Connecticut Health Center1, University of California, Berkeley2, Lawrence Berkeley National Laboratory3, National Institutes of Health4, Washington University in St. Louis5, Indiana University6, Cold Spring Harbor Laboratory7, Amgen8, Life Technologies9, Stowers Institute for Medical Research10, University of Kansas11, University of California, Santa Cruz12, Howard Hughes Medical Institute13, Affymetrix14
TL;DR: 111,195 new elements are identified, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events and inferred protein isoforms that previously eluded discovery using established experimental, prediction and conservation-based approaches.
Abstract: Drosophila melanogaster is one of the most well studied genetic model organisms; nonetheless, its genome still contains unannotated coding and non-coding genes, transcripts, exons and RNA editing sites. Full discovery and annotation are pre-requisites for understanding how the regulation of transcription, splicing and RNA editing directs the development of this complex organism. Here we used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages. We identified 111,195 new elements, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events, and inferred protein isoforms that previously eluded discovery using established experimental, prediction and conservation-based approaches. These data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout development.
1,427 citations
TL;DR: There is substantial evidence to support interventions for attention, memory, social communication skills, executive function, and for comprehensive-holistic neuropsychologic rehabilitation after TBI and stroke.
1,379 citations
05 Jul 2011
TL;DR: It is demonstrated that the network of political retweets exhibits a highly segregated partisan structure, with extremely limited connectivity between left- and right-leaning users, and surprisingly this is not the case for the user-to-user mention network, which is dominated by a single politically heterogeneous cluster of users.
Abstract: In this study we investigate how social media shape the networked public sphere and facilitate communication between communities with different political orientations. We examine two networks of political communication on Twitter, comprised of more than 250,000 tweets from the six weeks leading up to the 2010 U.S. congressional midterm elections. Using a combination of network clustering algorithms and manually-annotated data we demonstrate that the network of political retweets exhibits a highly segregated partisan structure, with extremely limited connectivity between left- and right-leaning users. Surprisingly this is not the case for the user-to-user mention network, which is dominated by a single politically heterogeneous cluster of users in which ideologically-opposed individuals interact at a much higher rate compared to the network of retweets. To explain the distinct topologies of the retweet and mention networks we conjecture that politically motivated individuals provoke interaction by injecting partisan content into information streams whose primary audience consists of ideologically-opposed users. We conclude with statistical evidence in support of this hypothesis.
1,379 citations
TL;DR: These findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer and demonstrate that cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, it is shown that tumor regression required macrophages but not T cells or gemcitabine.
Abstract: Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.
Book•
20 Jan 2011TL;DR: This week’s citation classicmarch 23, 1981 is a reexamination of its the 'superstition' experiment: a reversible figure causality and contingency: some conceptual considerations superstitious behavior classroom game teaching.
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Technische Universität München1, Novosibirsk State University2, Cornell University3, Lawrence Livermore National Laboratory4, University of California, Davis5, Argonne National Laboratory6, Fermilab7, Florida State University8, Indiana University9, Brookhaven National Laboratory10, Wayne State University11, University of Paris-Sud12, GSI Helmholtz Centre for Heavy Ion Research13, Ohio State University14, University of Regensburg15, University of Ferrara16, Polish Academy of Sciences17, University of Bari18, Max Planck Society19, Lancaster University20, Peking University21, Thomas Jefferson National Accelerator Facility22, University of Auvergne23, University of Cincinnati24, Stanford University25, University of Alberta26, Forschungszentrum Jülich27, University of Hawaii28, Illinois Institute of Technology29, Lawrence Berkeley National Laboratory30, École Polytechnique31, Budker Institute of Nuclear Physics32, CERN33, Université catholique de Louvain34, Pratt Institute35, University of São Paulo36, Seoul National University37, Tsinghua University38, Stony Brook University39, University of Valencia40, University of Milan41, Tohoku University42, University of Minnesota43
TL;DR: The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress as mentioned in this paper.
Abstract: A golden age for heavy-quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the B-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations at BESIII, the LHC, RHIC, FAIR, the Super Flavor and/or Tau-Charm factories, JLab, the ILC, and beyond. The list of newly found conventional states expanded to include h(c)(1P), chi(c2)(2P), B-c(+), and eta(b)(1S). In addition, the unexpected and still-fascinating X(3872) has been joined by more than a dozen other charmonium- and bottomonium-like "XYZ" states that appear to lie outside the quark model. Many of these still need experimental confirmation. The plethora of new states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c (c) over bar, b (b) over bar, and b (c) over bar bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. Lattice QCD has grown from a tool with computational possibilities to an industrial-strength effort now dependent more on insight and innovation than pure computational power. New effective field theories for the description of quarkonium in different regimes have been developed and brought to a high degree of sophistication, thus enabling precise and solid theoretical predictions. Many expected decays and transitions have either been measured with precision or for the first time, but the confusing patterns of decays, both above and below open-flavor thresholds, endure and have deepened. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.
TL;DR: In this article, measured and derived values of coefficients for Lorentz and $CPT$ violation in the standard-model extension are tabulated and summary tables are extracted listing maximal attained sensitivities in the matter, photon, and gravity sectors.
Abstract: This work tabulates measured and derived values of coefficients for Lorentz and $CPT$ violation in the standard-model extension. Summary tables are extracted listing maximal attained sensitivities in the matter, photon, and gravity sectors. Tables presenting definitions and properties are also compiled.
TL;DR: An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4, and a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals was identified.
Abstract: We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10−7). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.
Mayo Clinic1, New York University2, University of Hamburg3, Children's National Medical Center4, University of Girona5, Johns Hopkins University6, St George's, University of London7, Harvard University8, University of Ottawa9, University of Toronto10, University of Miami11, University of Paris12, University College London13, University of Münster14, University of Sydney15, Cincinnati Children's Hospital Medical Center16, University of Oxford17, University of Amsterdam18, Indiana University19
TL;DR: This dissertation aims to provide a history of modern medicine and some of the techniques and practices used in modern medicine, as well as some new approaches, that were introduced in the field of medicine more than 40 years ago.
TL;DR: Among patients receiving opioid prescriptions for pain, higher opioid doses were associated with increased risk of opioid overdose death, and receiving both as-needed and regularly scheduled doses was not associated with overdose risk after adjustment.
Abstract: Context The rate of prescription opioid–related overdose death increased substantially in the United States over the past decade. Patterns of opioid prescribing may be related to risk of overdose mortality. Objective To examine the association of maximum prescribed daily opioid dose and dosing schedule (“as needed,” regularly scheduled, or both) with risk of opioid overdose death among patients with cancer, chronic pain, acute pain, and substance use disorders. Design Case-cohort study. Setting Veterans Health Administration (VHA), 2004 through 2008. Participants All unintentional prescription opioid overdose decedents (n = 750) and a random sample of patients (n = 154 684) among those individuals who used medical services in 2004 or 2005 and received opioid therapy for pain. Main Outcome Measure Associations of opioid regimens (dose and schedule) with death by unintentional prescription opioid overdose in subgroups defined by clinical diagnoses, adjusting for age group, sex, race, ethnicity, and comorbid conditions. Results The frequency of fatal overdose over the study period among individuals treated with opioids was estimated to be 0.04%.The risk of overdose death was directly related to the maximum prescribed daily dose of opioid medication. The adjusted hazard ratios (HRs) associated with a maximum prescribed dose of 100 mg/d or more, compared with the dose category 1 mg/d to less than 20 mg/d, were as follows: among those with substance use disorders, adjusted HR = 4.54 (95% confidence interval [CI], 2.46-8.37; absolute risk difference approximation [ARDA] = 0.14%); among those with chronic pain, adjusted HR = 7.18 (95% CI, 4.85-10.65; ARDA = 0.25%); among those with acute pain, adjusted HR = 6.64 (95% CI, 3.31-13.31; ARDA = 0.23%); and among those with cancer, adjusted HR = 11.99 (95% CI, 4.42-32.56; ARDA = 0.45%). Receiving both as-needed and regularly scheduled doses was not associated with overdose risk after adjustment. Conclusion Among patients receiving opioid prescriptions for pain, higher opioid doses were associated with increased risk of opioid overdose death.
TL;DR: This article found that African American and Latino students are more likely than their white peers to receive expulsion or out-of-school suspension as consequences for the same or similar problem behavior, and argued for direct efforts in policy, practice, and research to address ubiquitous racial and ethnic disparities in school discipline.
Abstract: Discipline practices in schools affect the social quality of each educa- tional environment, and the ability of children to achieve the academic and social gains essential for success in a 21st century society. We review the documented patterns of office discipline referrals in 364 elementary and middle schools during the 2005-2006 academic year. Data were reported by school personnel through daily or weekly uploading of office discipline referrals using the Web-based School-wide Information System. Descriptive and logistic regression analyses indicate that students from African American families are 2.19 (elementary) to 3.78 (middle) times as likely to be referred to the office for problem behavior as their White peers. In addition, the results indicate that students from African American and Latino families are more likely than their White peers to receive expulsion or out of school suspension as consequences for the same or similar problem behavior. These results extend and are consistent with a long history of similar findings, and argue for direct efforts in policy, practice, and research to address ubiquitous racial and ethnic disparities in school discipline.
TL;DR: The authors provides an overview of the structure and evolution of the Institutional Analysis and Development (IAD) framework and a short introduction to its use by scholars to analyze a diversity of puzzles.
Abstract: This article provides an overview of the structure and evolution of the Institutional Analysis and Development (IAD) framework and a short introduction to its use by scholars to analyze a diversity of puzzles. It then addresses the relationship of IAD to a more complex framework for the analysis of social-ecological systems and concludes with a short discussion of future challenges facing IAD scholars.
Indiana University1, University of Notre Dame2, Utah State University3, University of New Hampshire4, University of California, Santa Barbara5, University of Tokyo6, United States Department of Energy7, Ludwig Maximilian University of Munich8, National Institutes of Health9, J. Craig Venter Institute10, University of Illinois at Urbana–Champaign11, Hebrew University of Jerusalem12, University of North Texas13, Harvard University14, University of Geneva15, Research Institute of Molecular Pathology16, Oregon State University17, Utrecht University18, University of California, Davis19, University of Iowa20, Hoffmann-La Roche21, University of Strasbourg22, University of Washington23, University of Texas at Arlington24, University of California, Santa Cruz25, Life Technologies26, New York University27, University of Guelph28, Imperial College London29, University of California, Berkeley30
TL;DR: The Daphnia genome reveals a multitude of genes and shows adaptation through gene family expansions, and the coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random.
Abstract: We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.
TL;DR: Current empirical efforts toward generating a network map of the human brain, the human connectome, are reviewed, and how the connectome can provide new insights into the organization of the brain's structural connections and their role in shaping functional dynamics are explored.
Abstract: The human brain is a complex network. An important first step toward understanding the function of such a network is to map its elements and connections, to create a comprehensive structural description of the network architecture. This paper reviews current empirical efforts toward generating a network map of the human brain, the human connectome, and explores how the connectome can provide new insights into the organization of the brain's structural connections and their role in shaping functional dynamics. Network studies of structural connectivity obtained from noninvasive neuroimaging have revealed a number of highly nonrandom network attributes, including high clustering and modularity combined with high efficiency and short path length. The combination of these attributes simultaneously promotes high specialization and high integration within a modular small-world architecture. Structural and functional networks share some of the same characteristics, although their relationship is complex and nonlinear. Future studies of the human connectome will greatly expand our knowledge of network topology and dynamics in the healthy, developing, aging, and diseased brain.
TL;DR: The Society for Vascular Surgery and the American Venous Forum have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis, including recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases.
Mayo Clinic1, New York University2, University of Hamburg3, George Washington University4, University of Girona5, Johns Hopkins University6, St George's, University of London7, Harvard University8, University of Ottawa9, Hospital for Sick Children10, University of Miami11, Paris Descartes University12, University College London13, University of Sydney14, Cincinnati Children's Hospital Medical Center15, John Radcliffe Hospital16, University of Amsterdam17, Indiana University18
TL;DR: This international consensus statement provides the state of genetic testing for the channelopathy and cardiomyopathies and summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the use and role of geneticTesting for these potentially heritable cardiac conditions.
Abstract: This international consensus statement provides the state of genetic testing for the channelopathies and cardiomyopathies. It summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the use and role of genetic testing for these potentially heritable cardiac conditions. This document focuses primarily on the state of genetic testing for the 13 distinct entities detailed and the relative diagnostic, prognostic, and therapeutic impact of the genetic test result for each entity. It does not focus on the therapeutic management of the various channelopathies and cardiomyopathies. Treatment/management issues are only discussed for those diseases (i.e., LQTS, HCM, DCM + CCD, RCM) in which the genetic test result could potentially influence treatment considerations.
Writing recommendations for genetic diseases require adaptation of the methodology normally adopted to prepare guidelines for clinical practice. Documents produced by other scientific societies have acknowledged the need to define the criteria used to rank the strength of recommendation for genetic diseases.1
The most obvious difference is that randomized and/or blinded studies do not exist. Instead, most of the available data are derived from registries that have followed patients and recorded outcome information. The authors of this statement have therefore defined specific criteria for Class I, Class IIa or b, and Class III recommendations and have used the conventional language adopted by AHA/ACC/ESC Guidelines to express each class. All recommendations are level of evidence (LOE) C (i.e., based on experts' opinions).
A Class I recommendation ( “is recommended” ) was applied for genetic testing in index cases with a sound clinical suspicion for the presence of a channelopathy or a cardiomyopathy when the positive predictive value of a genetic test is high (likelihood of positive result >40% and signal/noise ratio >10; Table 3), AND/OR when …
The Royal Marsden NHS Foundation Trust1, University of Texas MD Anderson Cancer Center2, Duke University3, Stanford University4, Cancer Research UK5, University of Pennsylvania6, Harvard University7, Peter MacCallum Cancer Centre8, University of Chicago9, Memorial Sloan Kettering Cancer Center10, Queen Mary University of London11, University College London12, Indiana University13, University Health Network14, Imperial College London15, University of Melbourne16
TL;DR: Nine major recommendations that should be taken to improve the outcome for women with ovarian cancer are outlined in this Opinion article.
Abstract: There have been major advances in our understanding of the cellular and molecular biology of the human malignancies that are collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Opinion article.
University of North Texas1, East Malling Research Station2, Plant & Food Research3, Oregon State University4, University of Maryland, College Park5, Indiana University6, Virginia Tech7, Georgia Institute of Technology8, University of New Hampshire9, United States Department of Agriculture10, Hoffmann-La Roche11, University of Auckland12, Rutgers University13, University of the Western Cape14, University of Florida15, University of Chile16, Andrés Bello National University17, Weizmann Institute of Science18, University of Pittsburgh19, University of Georgia20, Technische Universität München21, University of Illinois at Urbana–Champaign22, Institut national de la recherche agronomique23
TL;DR: New phylogenetic analysis of 154 protein-coding genes suggests that assignment of Populus to Malvidae, rather than Fabidae, is warranted, and macrosyntenic relationships between Fragaria and Prunus predict a hypothetical ancestral Rosaceae genome that had nine chromosomes.
Abstract: The woodland strawberry, Fragaria vesca (2n = 2x = 14), is a versatile experimental plant system. This diminutive herbaceous perennial has a small genome (240 Mb), is amenable to genetic transformation and shares substantial sequence identity with the cultivated strawberry (Fragaria × ananassa) and other economically important rosaceous plants. Here we report the draft F. vesca genome, which was sequenced to ×39 coverage using second-generation technology, assembled de novo and then anchored to the genetic linkage map into seven pseudochromosomes. This diploid strawberry sequence lacks the large genome duplications seen in other rosids. Gene prediction modeling identified 34,809 genes, with most being supported by transcriptome mapping. Genes critical to valuable horticultural traits including flavor, nutritional value and flowering time were identified. Macrosyntenic relationships between Fragaria and Prunus predict a hypothetical ancestral Rosaceae genome that had nine chromosomes. New phylogenetic analysis of 154 protein-coding genes suggests that assignment of Populus to Malvidae, rather than Fabidae, is warranted.
TL;DR: Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and invasion, is central to the pathophysiology of bone metastases.
Abstract: When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and to promote bone invasion. Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and invasion, is central to the pathophysiology of bone metastases. Basic findings of tumour–bone interactions have uncovered numerous therapeutic opportunities that focus on the bone microenvironment to prevent and treat bone metastases.
Indiana University1, Pasteur Institute2, Washington University in St. Louis3, University of British Columbia4, Cubist Pharmaceuticals5, University of Turku6, Lahey Hospital & Medical Center7, Harvard University8, University of Medicine and Dentistry of New Jersey9, The Evergreen State College10, Wayne State University11, Tufts University12, Northeastern University13, University of California, Los Angeles14, University of Notre Dame15, University of Birmingham16, MedImmune17, Rockefeller University18, Université catholique de Louvain19, Cardiff University20, Cold Spring Harbor Laboratory21, Robert Koch Institute22, McMaster University23, University of Oklahoma24
TL;DR: To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011.
Abstract: The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable but can nevertheless be controlled, and it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011. From these discussions there emerged a priority list of steps that need to be taken to resolve this global crisis.
Columbia University1, Georgetown University2, University of North Carolina at Chapel Hill3, University of California, San Diego4, World Bank5, United States Agency for International Development6, Harvard University7, Moi University8, Indiana University9, Massachusetts Institute of Technology10, Mbarara University of Science and Technology11
TL;DR: It is suggested that SMS reminders may be an important tool to achieve optimal treatment response in resource-limited settings and be used to promote high adherence to antiretroviral therapy.
Abstract: This brief summarizes the results of a gender impact evaluation study, entitled Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting : a randomized controlled trial of text message reminders, conducted between June 2007 to August 2008 in Kenya. The study observed that there is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy (ART). This study tested the efficacy of short message service (SMS) reminders on adherence to ART among patients attending a rural clinic in Kenya. In intention-to-treat analysis, 53 percent of participants receiving weekly SMS reminders achieved adherence of at least 90 percent during the 48 weeks of the study, compared with 40 percent of participants in the control group, the difference is significant. Funding for the study derived from the World Bank Research Group, Bank-Netherlands Partnership Program, USAID AMPATH Partnership, National Institute of Mental Health.
Columbia University1, University of California, San Diego2, Johns Hopkins University3, Indiana University4, University of Washington5, University of California, San Francisco6, Boston Children's Hospital7, Virginia Commonwealth University8, Washington University in St. Louis9, National Institutes of Health10
TL;DR: Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD.
Abstract: Context Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis (NASH). No treatment has been established. Objective To determine whether children with NAFLD would improve from therapeutic intervention with vitamin E or metformin. Design, Setting, and Patients Randomized, double-blind, double-dummy, placebo-controlled clinical trial conducted at 10 university clinical research centers in 173 patients (aged 8-17 years) with biopsy-confirmed NAFLD conducted between September 2005 and March 2010. Interventions Daily dosing of 800 IU of vitamin E (58 patients), 1000 mg of metformin (57 patients), or placebo (58 patients) for 96 weeks. Main Outcome Measures The primary outcome was sustained reduction in alanine aminotransferase (ALT) defined as 50% or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment. Improvements in histological features of NAFLD and resolution of NASH were secondary outcome measures. Results Sustained reduction in ALT level was similar to placebo (10/58; 17%; 95% CI, 9% to 29%) in both the vitamin E (15/58; 26%; 95% CI, 15% to 39%; P = .26) and metformin treatment groups (9/57; 16%; 95% CI, 7% to 28%; P = .83). The mean change in ALT level from baseline to 96 weeks was −35.2 U/L (95% CI, −56.9 to −13.5) with placebo vs −48.3 U/L (95% CI, −66.8 to −29.8) with vitamin E (P = .07) and −41.7 U/L (95% CI, −62.9 to −20.5) with metformin (P = .40). The mean change at 96 weeks in hepatocellular ballooning scores was 0.1 with placebo (95% CI, −0.2 to 0.3) vs −0.5 with vitamin E (95% CI, −0.8 to −0.3; P = .006) and −0.3 with metformin (95% CI, −0.6 to −0.0; P = .04); and in NAFLD activity score, −0.7 with placebo (95% CI, −1.3 to −0.2) vs −1.8 with vitamin E (95% CI, −2.4 to −1.2; P = .02) and −1.1 with metformin (95% CI, −1.7 to −0.5; P = .25). Among children with NASH, the proportion who resolved at 96 weeks was 28% with placebo (95% CI, 15% to 45%; 11/39) vs 58% with vitamin E (95% CI, 42% to 73%; 25/43; P = .006) and 41% with metformin (95% CI, 26% to 58%; 16/39; P = .23). Compared with placebo, neither therapy demonstrated significant improvements in other histological features. Conclusion Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD. Trial Registration clinicaltrials.gov Identifier: NCT00063635
Emory University1, University of Texas Southwestern Medical Center2, University of Utah3, Indiana University4, Stanford University5, Yale University6, Duke University7, Tufts University8, Wayne State University9, University of Texas Health Science Center at Houston10, University of Alabama at Birmingham11, University of New Mexico12, University of Iowa13, Case Western Reserve University14, University of Cincinnati15, Brown University16, Centers for Disease Control and Prevention17, National Institutes of Health18
TL;DR: In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease, suggesting that Escherichia coli is an important EO pathogen.
Abstract: BACKGROUND: Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen. OBJECTIVE: To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers. METHODS: Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ≤72 hours plus treatment with antibiotic therapy for ≥5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence. RESULTS: Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%). CONCLUSION: In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge.