Showing papers by "Tulane University published in 2016"
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
5,187 citations
TL;DR: Global hypertension disparities are large and increasing and collaborative efforts are urgently needed to combat the emerging hypertension burden in low- and middle-income countries.
Abstract: Background:Hypertension is the leading preventable cause of premature death worldwide. We examined global disparities of hypertension prevalence, awareness, treatment, and control in 2010 and compa...
2,062 citations
James Bentham1, Mariachiara Di Cesare2, Mariachiara Di Cesare1, Gretchen A Stevens3 +787 more•Institutions (246)
TL;DR: The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
Abstract: Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
1,348 citations
Wake Forest University1, University of Utah2, Veterans Health Administration3, Boston University4, Medical University of South Carolina5, Stanford University6, Mayo Clinic7, University of California, San Diego8, Rutgers University9, Tulane University10, National Institutes of Health11, University of Alabama at Birmingham12, Vanderbilt University13, United States Department of Veterans Affairs14, University of Florida15, Medical College of Wisconsin16, Case Western Reserve University17
TL;DR: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBp target of more than 140mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause.
Abstract: Importance The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. Objective To evaluate the effects of intensive ( Design, Setting, and Participants A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. Interventions Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). Main Outcomes and Measures The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. Results Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). Conclusions and Relevance Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. Trial Registration clinicaltrials.gov Identifier:NCT01206062
966 citations
Memorial Sloan Kettering Cancer Center1, University of Chicago2, University of Washington3, University of North Carolina at Chapel Hill4, Université Paris-Saclay5, Johns Hopkins University6, Oregon Health & Science University7, University of British Columbia8, University of Texas MD Anderson Cancer Center9, University of Virginia10, Duke University11, Wayne State University12, University of Michigan13, Thomas Jefferson University14, University of Wisconsin-Madison15, Cornell University16, Rutgers University17, University of California, San Francisco18, Tulane University19, Harvard University20, Columbia University21
TL;DR: The concept of no longer clinically benefiting is introduced to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions.
Abstract: PurposeEvolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups.MethodsAn international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.ResultsPCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as tim...
938 citations
Wageningen University and Research Centre1, University of Puerto Rico2, University of Alabama3, National Autonomous University of Mexico4, Brown University5, University of Connecticut6, University of São Paulo7, Leipzig University8, Smithsonian Tropical Research Institute9, Federal University of Pernambuco10, Tulane University11, University of Stirling12, Clemson University13, University of Alberta14, National Institute of Amazonian Research15, Colorado Mesa University16, State University of New York at Purchase17, World Agroforestry Centre18, University of Wisconsin-Madison19, Aarhus University20, Columbia University21, University of Minnesota22, University of California, Santa Barbara23, Pedagogical and Technological University of Colombia24, University of Maryland, College Park25, National University of Singapore26, Yale-NUS College27, Puerto Rico Department of Agriculture28, University of Amsterdam29, Museu Paraense Emílio Goeldi30, Louisiana State University31, University of Regina32
TL;DR: A biomass recovery map of Latin America is presented, which illustrates geographical and climatic variation in carbon sequestration potential during forest regrowth and will support policies to minimize forest loss in areas where biomass resilience is naturally low and promote forest regeneration and restoration in humid tropical lowland areas with high biomass resilience.
Abstract: Land-use change occurs nowhere more rapidly than in the tropics, where the imbalance between deforestation and forest regrowth has large consequences for the global carbon cycle. However, considerable uncertainty remains about the rate of biomass recovery in secondary forests, and how these rates are influenced by climate, landscape, and prior land use. Here we analyse aboveground biomass recovery during secondary succession in 45 forest sites and about 1,500 forest plots covering the major environmental gradients in the Neotropics. The studied secondary forests are highly productive and resilient. Aboveground biomass recovery after 20 years was on average 122 megagrams per hectare (Mg ha(-1)), corresponding to a net carbon uptake of 3.05 Mg C ha(-1) yr(-1), 11 times the uptake rate of old-growth forests. Aboveground biomass stocks took a median time of 66 years to recover to 90% of old-growth values. Aboveground biomass recovery after 20 years varied 11.3-fold (from 20 to 225 Mg ha(-1)) across sites, and this recovery increased with water availability (higher local rainfall and lower climatic water deficit). We present a biomass recovery map of Latin America, which illustrates geographical and climatic variation in carbon sequestration potential during forest regrowth. The map will support policies to minimize forest loss in areas where biomass resilience is naturally low (such as seasonally dry forest regions) and promote forest regeneration and restoration in humid tropical lowland areas with high biomass resilience.
724 citations
Baylor College of Medicine1, Beth Israel Deaconess Medical Center2, Emory University3, Ochsner Medical Center4, Icahn School of Medicine at Mount Sinai5, Cedars-Sinai Medical Center6, University of Tennessee Health Science Center7, University of Texas Health Science Center at San Antonio8, American Association of Clinical Endocrinologists9, Tulane University10, University of Alabama at Birmingham11, Wayne State University12, The American College of Financial Services13, University of California, San Diego14, University of Washington15, University of Miami16, Washington University in St. Louis17, University of California, Irvine18
TL;DR: This chapter discusses the development and use of eicosapentaenoic acid as a treatment for diabetic ketoacidosis and its applications in conventional and regenerative medicine.
680 citations
University of California, Los Angeles1, University of California, Santa Barbara2, University of New Mexico3, University of Southern California4, National Institutes of Health5, Tulane University6, Centre national de la recherche scientifique7, Harvard University8, University of British Columbia9, Stanford University10, VA Palo Alto Healthcare System11, Fred Hutchinson Cancer Research Center12, University of Washington13
TL;DR: Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes.
Abstract: Epigenetic biomarkers of aging (the “epigenetic clock”) have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors. We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue. Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.
510 citations
TL;DR: In this article, the authors describe a calibration procedure developed during the Cosmic-Ray Produced Nuclide Systematics on Earth (CRONUS-Earth) project and its application to an extensive data set that included both new cosmogenic nuclide samples and samples from previously published studies.
505 citations
University of Cambridge1, Mansfield University of Pennsylvania2, Imperial College London3, Fritz Haber Institute of the Max Planck Society4, University of Graz5, University of Bonn6, University of Southampton7, Radboud University Nijmegen8, Princeton University9, Panjab University, Chandigarh10, University of Toronto11, Tulane University12, Carnegie Mellon University13, Cornell University14, Utrecht University15, OpenEye Scientific Software16, University of Utah17, Facultad de Ciencias Exactas y Naturales18, Toyohashi University of Technology19, University College London20, Polaris Industries21, University of Silesia in Katowice22, Argonne National Laboratory23, Rutgers University24, Max Planck Society25, University of Luxembourg26, New York University27, Courant Institute of Mathematical Sciences28, New York University Shanghai29, Loyola University Chicago30
TL;DR: The results of the sixth blind test of organic crystal structure prediction methods are presented and discussed, highlighting progress for salts, hydrates and bulky flexible molecules, as well as on-going challenges.
Abstract: The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.
435 citations
International Institute of Minnesota1, University of Connecticut2, University of Alabama3, Wageningen University and Research Centre4, University of Regina5, University of Puerto Rico6, National Autonomous University of Mexico7, Brown University8, University of São Paulo9, Smithsonian Tropical Research Institute10, Leipzig University11, Federal University of Pernambuco12, Tulane University13, University of Stirling14, Clemson University15, University of Alberta16, National Institute of Amazonian Research17, Colorado Mesa University18, State University of New York at Purchase19, World Agroforestry Centre20, Columbia University21, Aarhus University22, University of Minnesota23, University of California, Santa Barbara24, Pedagogical and Technological University of Colombia25, University of Maryland, College Park26, National University of Singapore27, Yale-NUS College28, Puerto Rico Department of Agriculture29, University of Amsterdam30, Museu Paraense Emílio Goeldi31, Louisiana State University32
TL;DR: This study estimates the age and spatial extent of lowland second-growth forests in the Latin American tropics and model their potential aboveground carbon accumulation over four decades to guide national-level forest-based carbon mitigation plans.
Abstract: Regrowth of tropical secondary forests following complete or nearly complete removal of forest vegetation actively stores carbon in aboveground biomass, partially counterbalancing carbon emissions from deforestation, forest degradation, burning of fossil fuels, and other anthropogenic sources. We estimate the age and spatial extent of lowland second-growth forests in the Latin American tropics and model their potential aboveground carbon accumulation over four decades. Our model shows that, in 2008, second-growth forests (1 to 60 years old) covered 2.4 million km2 of land (28.1% of the total study area). Over 40 years, these lands can potentially accumulate a total aboveground carbon stock of 8.48 Pg C (petagrams of carbon) in aboveground biomass via low-cost natural regeneration or assisted regeneration, corresponding to a total CO2 sequestration of 31.09 Pg CO2. This total is equivalent to carbon emissions from fossil fuel use and industrial processes in all of Latin America and the Caribbean from 1993 to 2014. Ten countries account for 95% of this carbon storage potential, led by Brazil, Colombia, Mexico, and Venezuela. We model future land-use scenarios to guide national carbon mitigation policies. Permitting natural regeneration on 40% of lowland pastures potentially stores an additional 2.0 Pg C over 40 years. Our study provides information and maps to guide national-level forest-based carbon mitigation plans on the basis of estimated rates of natural regeneration and pasture abandonment. Coupled with avoided deforestation and sustainable forest management, natural regeneration of second-growth forests provides a low-cost mechanism that yields a high carbon sequestration potential with multiple benefits for biodiversity and ecosystem services.
TL;DR: The NHS cohorts have contributed to the understanding of the risk factors for and consequences of obesity and made a lasting impact on clinical and public health guidelines on obesity prevention.
Abstract: Objectives. To review the contribution of the Nurses’ Health Studies (NHS and NHS II) in addressing hypotheses regarding risk factors for and consequences of obesity.Methods. Narrative review of the publications of the NHS and NHS II between 1976 and 2016.Results. Long-term NHS research has shown that weight gain and being overweight or obese are important risk factors for type 2 diabetes, cardiovascular diseases, certain types of cancers, and premature death. The cohorts have elucidated the role of dietary and lifestyle factors in obesity, especially sugar-sweetened beverages, poor diet quality, physical inactivity, prolonged screen time, short sleep duration or shift work, and built environment characteristics. Genome-wide association and gene–lifestyle interaction studies have shown that genetic factors predispose individuals to obesity but that such susceptibility can be attenuated by healthy lifestyle choices. This research has contributed to evolving clinical and public health guidelines on the impo...
TL;DR: A meta-analysis of genome-wide association studies for estimated glomerular filtration rate suggests that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
TL;DR: ZrSiSe and ZrSiTe single crystals can be thinned down to 2D atomic thin layers through microexfoliation, which offers the first platform to explore exotic properties of topological nodal-line fermions in low dimensions.
Abstract: A Dirac nodal-line semimetal phase, which represents a new quantum state of topological materials, has been experimentally realized only in a few systems, including PbTaSe_{2}, PtSn_{4}, and ZrSiS. In this Letter, we report evidence of nodal-line fermions in ZrSiSe and ZrSiTe probed in de Haas-van Alphen quantum oscillations. Although ZrSiSe and ZrSiTe share a similar layered structure with ZrSiS, our studies show the Fermi surface (FS) enclosing a Dirac nodal line has a 2D character in ZrSiTe, in contrast with 3D-like FS in ZrSiSe and ZrSiS. Another important property revealed in our experiment is that the nodal-line fermion density in this family of materials (∼10^{20} cm^{-3}) is much higher than the Dirac fermion density of other topological materials with discrete nodes. In addition, we have demonstrated ZrSiSe and ZrSiTe single crystals can be thinned down to 2D atomic thin layers through microexfoliation, which offers the first platform to explore exotic properties of topological nodal-line fermions in low dimensions.
University of Pittsburgh1, University of Edinburgh2, University of Birmingham3, Baylor University Medical Center4, University of California, San Francisco5, Queen Elizabeth Hospital Birmingham6, Harvard University7, Royal Prince Alfred Hospital8, Cleveland Clinic9, Oslo University Hospital10, Kyoto University11, University Health Network12, Mayo Clinic13, Mount Sinai Hospital14, Icahn School of Medicine at Mount Sinai15, University of São Paulo16, University of Cambridge17, Columbia University18, Cincinnati Children's Hospital Medical Center19, Universidade Federal do Rio Grande do Sul20, Loma Linda University21, Ain Shams University22, Hospital of the University of Pennsylvania23, University Medical Center Groningen24, Toronto General Hospital25, University of Chicago26, Beni-Suef University27, Kobe University28, Temple University29, Lahey Hospital & Medical Center30, Duke University31, University of North Carolina at Chapel Hill32, University of California, Los Angeles33, Cliniques Universitaires Saint-Luc34, Northwestern University35, St. Joseph's Hospital and Medical Center36, Sahlgrenska University Hospital37, Beth Israel Deaconess Medical Center38, University of Kansas39, Hadassah Medical Center40, University of Southern California41, University of Miami42, Dokuz Eylül University43, University of Pennsylvania44, University of Alberta Hospital45, University of Texas Medical Branch46, University of Rome Tor Vergata47, University of Patras48, Karolinska University Hospital49, Tulane University50
TL;DR: New recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization are included.
Emory University1, University of Verona2, National Institutes of Health3, King's College London4, Queen Mary University of London5, University of Modena and Reggio Emilia6, Leiden University7, Center for Cell and Gene Therapy8, Tulane University9, University of Wisconsin-Madison10, Health Sciences Authority11, St George's Hospital12, Karolinska Institutet13, University Hospital of Basel14, University of Texas MD Anderson Cancer Center15, Agency for Science, Technology and Research16, University of Pittsburgh17, Scripps Research Institute18, French Institute of Health and Medical Research19, Chinese Academy of Sciences20, Soochow University (Suzhou)21, University Health Network22, University of Vermont23
TL;DR: The International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas as mentioned in this paper.
TL;DR: In this paper, the authors address the questions of whether and how corporate social responsibility (CSR) relates to firm performance and identify four mechanisms pertaining to this relationship: slack resources lead to CSR, CSR improves performance, CSI makes amends for past corporate social irresponsibility (CSI), and CSR insures against subsequent CSI (i.e., insurance mechanism).
Abstract: The authors address the questions of whether and how corporate social responsibility (CSR) relates to firm performance and, in so doing, identify four mechanisms pertaining to this relationship: (1) slack resources lead to CSR (i.e., slack resources mechanism) (2) CSR improves performance (i.e., good management mechanism), (3) CSR makes amends for past corporate social irresponsibility (CSI) (i.e., penance mechanism), and (4) CSR insures against subsequent CSI (i.e., insurance mechanism). Using an integrative approach, the authors incorporate the four mechanisms in their empirical model specification. Specifically, to model the interplay among CSR, CSI, and firm performance and to test the four mechanisms simultaneously, they propose a structural panel vector autoregression specification. In support of the good management mechanism, results from an unbalanced panel data set of more than 4,500 firms and up to 19 years suggest that firms that engage in CSR are likely to benefit financially from thei...
TL;DR: The authors examined the link between political uncertainty and firm investment using U.S. gubernatorial elections as a source of plausibly exogenous variation in uncertainty and found that firms delay SEOs tied to investments during higher uncertainty.
Abstract: I examine the link between political uncertainty and firm investment using U.S. gubernatorial elections as a source of plausibly exogenous variation in uncertainty. Investment declines 5% before all elections and up to 15% for subsamples of firms particularly susceptible to political uncertainty. I use term limits as an IV for election closeness. Because close elections are related to economic downturns, I find that the effect of close elections on investment is understated by more than half by OLS. Post-election rebounds in investment depend on whether an incumbent is re-elected. Finally, I provide evidence that firms delay SEOs tied to investments during higher uncertainty.
TL;DR: An essential 5-HTDRN→CRFBNST circuit governing fear and anxiety underlies aversive behaviour following acute exposure to selective serotonin reuptake inhibitors (SSRIs), and provides a potential mechanistic explanation for the clinical observation of early adverse events to SSRI treatment in some patients with anxiety disorders.
Abstract: Serotonin (also known as 5-hydroxytryptamine (5-HT)) is a neurotransmitter that has an essential role in the regulation of emotion. However, the precise circuits have not yet been defined through which aversive states are orchestrated by 5-HT. Here we show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety and activates a subpopulation of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminalis (CRFBNST) in mice. Specifically, 5-HTDRN projections to the BNST, via actions at 5-HT2C receptors (5-HT2CRs), engage a CRFBNST inhibitory microcircuit that silences anxiolytic BNST outputs to the ventral tegmental area and lateral hypothalamus. Furthermore, we demonstrate that this CRFBNST inhibitory circuit underlies aversive behaviour following acute exposure to selective serotonin reuptake inhibitors (SSRIs). This early aversive effect is mediated via the corticotrophin-releasing factor type 1 receptor (CRF1R, also known as CRHR1), given that CRF1R antagonism is sufficient to prevent acute SSRI-induced enhancements in aversive learning. These results reveal an essential 5-HTDRN→CRFBNST circuit governing fear and anxiety, and provide a potential mechanistic explanation for the clinical observation of early adverse events to SSRI treatment in some patients with anxiety disorders.
TL;DR: This work uses a formal model of code spillovers to show how a rising number of developers can invert the firm and to provide a theory of how platform firms optimize their own intellectual property regimes in order to maximize growth.
Abstract: For a period starting in 2015, Apple, Google, and Microsoft became the most valuable companies in the world. Each was marked by an external developer ecosystem. Anecdotally, at least, developers matter. Using a formal model of code spillovers, we show how a rising number of developers can invert the firm. That is, firms will choose to innovate using open external contracts in preference to closed vertical integration. The locus of value creation moves from inside the firm to outside. Distinct from physical goods, digital goods afford firms the chance to optimize spillovers. Further, firms that pursue high risk innovations with more developers can be more profitable than firms that pursue low risk innovations with fewer developers. More developers give platform firms more chances at success. Our contribution is to show why developers might cause a shift in organizational form and to provide a theory of how platform firms optimize their own intellectual property regimes in order to maximize growth. We use stylized facts from multiple platform firms to illustrate our theory and results.
TL;DR: A combined intervention that included oncologist communication training and coaching for patients with advanced cancer was effective in improving patient-centered communication but did not affect secondary outcomes.
Abstract: Importance Observational studies demonstrate links between patient-centered communication, quality of life (QOL), and aggressive treatments in advanced cancer, yet few randomized clinical trials (RCTs) of communication interventions have been reported. Objective To determine whether a combined intervention involving oncologists, patients with advanced cancer, and caregivers would promote patient-centered communication, and to estimate intervention effects on shared understanding, patient-physician relationships, QOL, and aggressive treatments in the last 30 days of life. Design, setting, and participants Cluster RCT at community- and hospital-based cancer clinics in Western New York and Northern California; 38 medical oncologists (mean age 44.6 years; 11 (29%) female) and 265 community-dwelling adult patients with advanced nonhematologic cancer participated (mean age, 64.4 years, 146 [55.0%] female, 235 [89%] white; enrolled August 2012 to June 2014; followed for 3 years); 194 patients had participating caregivers. Interventions Oncologists received individualized communication training using standardized patient instructors while patients received question prompt lists and individualized communication coaching to identify issues to address during an upcoming oncologist visit. Both interventions focused on engaging patients in consultations, responding to emotions, informing patients about prognosis and treatment choices, and balanced framing of information. Control participants received no training. Main outcomes and measures The prespecified primary outcome was a composite measure of patient-centered communication coded from audio recordings of the first oncologist visit following patient coaching (intervention group) or enrollment (control). Secondary outcomes included the patient-physician relationship, shared understanding of prognosis, QOL, and aggressive treatments and hospice use in the last 30 days of life. Results Data from 38 oncologists (19 randomized to intervention) and 265 patients (130 intervention) were analyzed. In fully adjusted models, the intervention resulted in clinically and statistically significant improvements in the primary physician-patient communication end point (adjusted intervention effect, 0.34; 95% CI, 0.06-0.62; P = .02). Differences in secondary outcomes were not statistically significant. Conclusions and relevance A combined intervention that included oncologist communication training and coaching for patients with advanced cancer was effective in improving patient-centered communication but did not affect secondary outcomes. Trial registration clinicaltrials.gov Identifier: NCT01485627.
TL;DR: In this paper, the literatures on trauma-informed approaches and multitiered frameworks for school-based service delivery are connected with the goal to provide suggestions toward building blueprints for trauma- informed service delivery in schools.
Abstract: Recognition of the benefits to trauma-informed approaches is expanding, along with commensurate interest in extending delivery within school systems. Although information about trauma-informed approaches has quickly burgeoned, systematic attention to integration within multitiered service delivery frameworks has not occurred yet is essential to accurate, durable, and scalable implementation. In addition, there is a critical need to concurrently build a strong evidence base regarding trauma-informed service delivery in schools. In this paper, the literatures on trauma-informed approaches and multitiered frameworks for school-based service delivery are connected with the goal to provide suggestions toward building blueprints for trauma-informed service delivery in schools. Drawing from the literature on implementation blueprints for school-wide positive behavior supports, sections are organized around current knowledge about trauma-informed approaches with regard to blueprints for (a) implementation, (b) professional development, and (c) evaluation. Critical issues, strategy recommendations, and directions for research are discussed.
The American College of Financial Services1, University of California, San Diego2, Icahn School of Medicine at Mount Sinai3, University of Tennessee Health Science Center4, University of Texas Health Science Center at San Antonio5, American Association of Clinical Endocrinologists6, Tulane University7, Baylor College of Medicine8, Emory University9, University of Maryland, Baltimore10
TL;DR: ABBREVIATIONS AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology DKA = diabetic ketoacidosis EMA = European Medicines Agency FDA = U.S. Food and Drug Administration SGLT-2 = sodium glucosecotransporter 2 T1D = type 1 diabetes T2D =type 2 diabetes.
TL;DR: This review presents macrophages as a cellular link that spatially and temporally connects angiogenesis with lymphangiogenesis, in both physiological growth and in pathological adaptations, such as tumorigenesis.
Abstract: Angiogenesis and lymphangiogenesis often occur in response to tissue injury or in the presence of pathology (e.g., cancer), and it is these types of environments in which macrophages are activated and increased in number. Moreover, the blood vascular microcirculation and the lymphatic circulation serve as the conduits for entry and exit for monocyte-derived macrophages in nearly every tissue and organ. Macrophages both affect and are affected by the vessels through which they travel. Therefore, it is not surprising that examination of macrophage behaviors in both angiogenesis and lymphangiogenesis has yielded interesting observations that suggest macrophages may be key regulators of these complex growth and remodeling processes. In this review, we will take a closer look at macrophages through the lens of angiogenesis and lymphangiogenesis, examining how their dynamic behaviors may regulate vessel sprouting and function. We present macrophages as a cellular link that spatially and temporally connects angiogenesis with lymphangiogenesis, in both physiological growth and in pathological adaptations, such as tumorigenesis. As such, attempts to therapeutically target macrophages in order to affect these processes may be particularly effective, and studying macrophages in both settings will accelerate the field's understanding of this important cell type in health and disease.
TL;DR: This study identified associations of overall microbial richness and 6 microbial genera with lifetime CVD risk among 55 Bogalusa Heart Study participants with the highest and 57 with the lowest lifetime burdens of CVDrisk factors.
Abstract: Rationale: Few studies have systematically assessed the influence of gut microbiota on cardiovascular disease (CVD) risk.
Objective: To examine the association between gut microbiota and lifetime CVD risk profile among 55 Bogalusa Heart Study (BHS) participants with the highest and 57 with the lowest lifetime burdens of CVD risk factors.
Methods and Results: 16S rRNA sequencing was conducted on microbial DNA extracted from stool samples of the BHS participants. Alpha diversity, including measures of richness and evenness, and individual genera were tested for associations with lifetime CVD risk profile. Multivariable regression techniques were employed to adjust for age, gender, and race (Model 1), along with body mass index (BMI) (Model 2) and both BMI and diet (Model 3). In Model 1, odds ratios (95% confidence intervals) for each standard deviation increase in richness, measured by the number of observed operational taxonomic units, Chao 1 index, and abundance-based coverage estimator, were 0.62 (0.39, 0.99), 0.61 (0.38, 0.98), and 0.63 (0.39, 0.99), respectively. Associations were consistent in Models 2 and 3. Four genera were enriched among those with high versus low CVD risk profile in all models. Model 1 p-values were: 2.12×10-3×10-5, 4.39×10-4, and 1.51×10-4 for Prevotella 2, Prevotella 7, Tyzzerella and Tyzzerella 4 , respectively. Two genera were depleted among those with high versus low CVD risk profile in all models. Model 1 P-values were: 2.96×10-6 and 1.82×10-4 for Alloprevotella and Catenibacterium , respectively.
Conclusions: The current study identified associations of overall microbial richness and six microbial genera with lifetime CVD risk.
Journal Article•
TL;DR: Activity of the Default Mode Network (DMN) in neurological and neuropsychiatric disorders, including Alzheimer's disease, Parkinson’s disease, Epilepsy, attention deficit hyperactivity disorder (ADHD), and mood disorders are reviewed.
Abstract: The relationship of cortical structure and specific neuronal circuitry to global brain function, particularly its perturbations related to the development and progression of neuropathology, is an area of great interest in neurobehavioral science. Disruption of these neural networks can be associated with a wide range of neurological and neuropsychiatric disorders. Herein we review activity of the Default Mode Network (DMN) in neurological and neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, Epilepsy (Temporal Lobe Epilepsy - TLE), attention deficit hyperactivity disorder (ADHD), and mood disorders. We discuss the implications of DMN disruptions and their relationship to the neurocognitive model of each disease entity, the utility of DMN assessment in clinical evaluation, and the changes of the DMN following treatment.
TL;DR: In this paper, the authors combined experimental and theoretical investigations on the electronic structure of WTe${}_{2}$ and revealed the existence of a surface state that connects the bulk electron and hole pockets.
Abstract: WTe${}_{2}$ is well known for its manifestation of anomalously large magnetoresistance. It has recently attracted much attention because it is theoretically predicted to be the first material candidate that may realize the ``type-II'' Weyl state. This work reports combined experimental and theoretical investigations on the electronic structure of WTe${}_{2}$. Taking advantage of the latest-generation laser-based angle-resolved photoemission (ARPES) system with superior instrumental resolution, a complete picture of the electronic structure of WTe${}_{2}$ is revealed. The existence of a surface state that connects the bulk electron and hole pockets is identified. High-temperature ARPES measurements make it possible to reveal electronic states above the Fermi level where the Weyl points are predicted to be located. The observed connection of the surface state with the bulk bands, its momentum evolution, and its momentum and energy locations, are all in good agreement with the calculated band structures. These results provide key information to understand the anomalous transport properties of WTe${}_{2}$. They also provide electronic signatures that are consistent with the type-II Weyl state in WTe${}_{2}$ and lay a foundation for further investigations on its topological nature.
Centre for Environment, Fisheries and Aquaculture Science1, United States Department of Agriculture2, Albert Einstein College of Medicine3, Canadian Institute for Advanced Research4, Tulane University5, University of Exeter6, University of Saint Mary7, Oregon State University8, Ross University School of Veterinary Medicine9, Royal Holloway, University of London10, University of California, San Diego11, International Livestock Research Institute12, Louisiana State University13, Texas A&M University14, University of Illinois at Urbana–Champaign15
TL;DR: Strong evidence exists for an increasing prevalence of microsporidiosis in animals and humans, and for sharing of pathogens across hosts and biomes.
TL;DR: The behavioral immune system as discussed by the authors is a motivational system that evolved as a means of inhibiting contact with disease-causing parasites and that, in contemporary human societies, influences social cognition and social behavior.
Abstract: The “behavioral immune system” is a motivational system that evolved as a means of inhibiting contact with disease-causing parasites and that, in contemporary human societies, influences social cognition and social behavior. In this chapter, we provide an overview of the behavioral immune system and how it works, along with a review of empirical research documenting its consequences for a wide range of social psychological phenomena—including person perception, interpersonal attraction, intergroup prejudice, social influence, and moral judgment. We also describe further consequences for health, for politics and public policy, and for cultural differences. Finally, we discuss a variety of broader implications—both practical and conceptual—and identify some important directions for future research.
TL;DR: This review chronicles the development of the unique, multidisciplinary field of endocrine disruption, highlighting what the authors have learned about the threat of EDCs and lessons that could be relevant to other fields.
Abstract: Within the past few decades, the concept of endocrine-disrupting chemicals (EDCs) has risen from a position of total obscurity to become a focus of dialogue, debate, and concern among scientists, physicians, regulators, and the public. The emergence and development of this field of study has not always followed a smooth path, and researchers continue to wrestle with questions about the low-dose effects and nonmonotonic dose responses seen with EDCs, their biological mechanisms of action, the true pervasiveness of these chemicals in our environment and in our bodies, and the extent of their effects on human and wildlife health. This review chronicles the development of the unique, multidisciplinary field of endocrine disruption, highlighting what we have learned about the threat of EDCs and lessons that could be relevant to other fields. It also offers perspectives on the future of the field and opportunities to better protect human health.