Showing papers by "Tulane University published in 2018"
Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4 +1025 more•Institutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).
5,211 citations
Jeffrey D. Stanaway1, Ashkan Afshin1, Emmanuela Gakidou1, Stephen S Lim1 +1050 more•Institutions (346)
TL;DR: This study estimated levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs) by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017 and explored the relationship between development and risk exposure.
2,910 citations
TL;DR: In insights into the role of alcohol consumption in the genetic architecture of hypertension, a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions is conducted.
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
1,218 citations
Xi'an Jiaotong University1, Huazhong University of Science and Technology2, Fudan University3, China Medical University (PRC)4, Guangzhou Medical University5, Zhejiang University6, Sichuan University7, Capital Medical University8, Peking University9, Peking Union Medical College10, China-Japan Friendship Hospital11, Beijing Jishuitan Hospital12, Tulane University13
TL;DR: Prevalence of spirometry-defined COPD is highly prevalent in the Chinese adult population and prevention and early detection of COPD using spirometry should be a public health priority in China to reduce COPD-related morbidity and mortality.
811 citations
TL;DR: Compared with the JNC7 guideline, the 2017 ACC/AHA guideline results in a substantial increase in the prevalence of hypertension, a small increase inThe percentage of US adults recommended for antihypertensive medication, and more intensive BP lowering for many adults taking antihyertensive medication.
736 citations
TL;DR: The current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies is reviewed and future research directions aimed at the elimination of these adverse factors, and the integration of measures of S ES into the customization of cardiovascular treatment are suggested.
Abstract: Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD) Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors In addition, disparities based on sex have been shown in several studies Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment
594 citations
University of Bern1, Institute of Cancer Research2, Oregon Health & Science University3, Cornell University4, Princess Margaret Cancer Centre5, Yonsei University6, University of Salford7, University of Copenhagen8, Monash University9, University of São Paulo10, Columbia University11, The Royal Marsden NHS Foundation Trust12, University of Texas MD Anderson Cancer Center13, University of California, Davis14, University of Bologna15, University of California, San Francisco16, University of Paris-Sud17, University of British Columbia18, Duke University19, University of Cologne20, Fred Hutchinson Cancer Research Center21, University of Birmingham22, Memorial Sloan Kettering Cancer Center23, University of Tampere24, American University of Beirut25, Medical University of Vienna26, Vanderbilt University27, Tata Memorial Hospital28, Icahn School of Medicine at Mount Sinai29, Ghent University30, University of Washington31, Université de Montréal32, Tulane University33, Tel Aviv University34, Harvard University35, Prostate Cancer Foundation36, Toho University37, University College London38, University of Toronto39, Université catholique de Louvain40, University of Milan41, University of Ulm42
TL;DR: The presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available.
539 citations
Stanford University1, Rigshospitalet2, Ludwig Maximilian University of Munich3, Karolinska Institutet4, Örebro University5, Masaryk University6, Leipzig University7, United States Department of Veterans Affairs8, Emory University9, Tulane University10, Golden Jubilee National Hospital11, University of Bern12, University of Toronto13
TL;DR: In patients with stable coronary artery disease, an initial FFR‐guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone.
Abstract: Background We hypothesized that fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. Methods Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. Results A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The dif...
534 citations
463 citations
Baylor College of Medicine1, Harvard University2, Emory University3, Kaiser Permanente4, Ochsner Medical Center5, Icahn School of Medicine at Mount Sinai6, University of California, Los Angeles7, Cedars-Sinai Medical Center8, University of Tennessee Health Science Center9, University of Texas Health Science Center at San Antonio10, American Association of Clinical Endocrinologists11, Tulane University12, University of Alabama at Birmingham13, University of Washington14, University of Miami15, Washington University in St. Louis16, Mount Sinai Hospital17, University of California, Irvine18, Grady Memorial Hospital19
TL;DR: The objective of the trial was to establish whether or not the initial treatment strategy improved the patient’s quality of life and/or lowered the risk of adverse events.
445 citations
TL;DR: In this paper, a noninvasive neuroimaging measure, T1w/T2w mapping, was used to identify a hierarchical axis linking cortical transcription and anatomy, along which gradients of micro-scale properties may contribute to the macroscale specialization of cortical function.
Abstract: Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet microscale bases of specialization across human cortex are poorly understood. Anatomical hierarchy is conventionally informed by invasive tract-tracing measurements, creating a need for a principled proxy measure in humans. Moreover, cortex exhibits marked interareal variation in gene expression, yet organizing principles of cortical transcription remain unclear. We hypothesized that specialization of cortical microcircuitry involves hierarchical gradients of gene expression. We found that a noninvasive neuroimaging measure—MRI-derived T1-weighted/T2-weighted (T1w/T2w) mapping—reliably indexes anatomical hierarchy, and it captures the dominant pattern of transcriptional variation across human cortex. We found hierarchical gradients in expression profiles of genes related to microcircuit function, consistent with monkey microanatomy, and implicated in neuropsychiatric disorders. Our findings identify a hierarchical axis linking cortical transcription and anatomy, along which gradients of microscale properties may contribute to the macroscale specialization of cortical function.
TL;DR: Interventions added to androgen-deprivation therapy in men with metastatic prostate cancer have recently been noted to increase survival.
Abstract: Metastatic Prostate Cancer Interventions added to androgen-deprivation therapy in men with metastatic prostate cancer have recently been noted to increase survival. Decisions about which treatments to use and in what order to maximize the benefit should be made on the basis of high-quality clinical trials.
TL;DR: In this paper, the authors find that the interaction of order-fulfillment costs and upstream competition intensity moderates the selection of an optimal mode for the intermediary, and that the hybrid mode is preferred when order fulfillment costs are moderate and suppliers' products are somewhat similar.
Abstract: Traditionally, online retailers have acted as product resellers. Recently, these retailers have also started to serve as online marketplaces by providing a platform to directly connect sellers with buyers. Over and above re‐shaping the traditional e‐commerce market, conventional wisdom suggests that this new format will mitigate the double‐marginalization effect and benefit both the intermediary and suppliers through a revenue sharing scheme. However, we find that upstream competition between suppliers critically moderates this possibility. We also find that the interaction of order‐fulfillment costs and upstream competition intensity moderates the selection of an optimal mode for the intermediary. More specifically, when order‐fulfillment costs are large and when the supplier product offerings are similar (i.e., competition intensity is high), the pure reseller mode is the preferred choice; when order‐fulfillment costs are small and the supplier product offerings are highly differentiated (i.e., low competition intensity), the pure marketplace mode is the preferred choice. Finally, the hybrid mode is preferred when order‐fulfillment costs are moderate and suppliers’ products are somewhat similar (i.e., competition intensity is moderate). The intuition behind these results hinges on the trade‐off between transfer of pricing rights and the responsibility for order fulfillment. Our findings not only complement the emerging online marketplace literature but also provide testable empirical questions concerning the relationship and magnitude of different factors steering the mode choice.
Christopher J L Murray1, Charlton S K H Callender1, Xie Rachel Kulikoff1, Vinay Srinivasan1 +1092 more•Institutions (424)
TL;DR: This work estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods and used the cohort-component method of population projection, with inputs of fertility, mortality, population, and migration data.
TL;DR: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults provides an evidence-based approach to reduction of CVD risk through lowering of blood pressure (BP).
Abstract: In November 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) released the guideline for the prevention, detection, evaluation, and treatment of high blood pre...
TL;DR: The results presented herein show that transition-metal carbide are promising co-catalysts for photocatalytic hydrogen production.
Abstract: Hydrogen production through facile photocatalytic water splitting is regarded as a promising strategy to solve global energy problems. Transition-metal carbides (MXenes) have recently drawn attention as potential co-catalyst candidates for photocatalysts. Here, we report niobium pentoxide/carbon/niobium carbide (MXene) hybrid materials (Nb2 O5 /C/Nb2 C) as photocatalysts for hydrogen evolution from water splitting. The Nb2 O5 /C/Nb2 C composites were synthesized by one-step CO2 oxidation of Nb2 CTx . Nb2 O5 grew homogeneously on Nb2 C after mild oxidation, during which some amorphous carbon was also formed. With an optimized oxidation time of 1.0 h, Nb2 O5 /C/Nb2 C showed the highest hydrogen generation rate (7.81 μmol h-1 gcat-1 ), a value that was four times higher than that of pure Nb2 O5 . The enhanced performance of Nb2 O5 /C/Nb2 C was attributed to intimate contact between Nb2 O5 and conductive Nb2 C and the separation of photogenerated charge carriers at the Nb2 O5 /Nb2 C interface; the results presented herein show that transition-metal carbide are promising co-catalysts for photocatalytic hydrogen production.
TL;DR: It is demonstrated how mitochondria coordinate to alter immune responses and how changes in mitochondrial machinery contribute to alterations in immune responses.
Abstract: Lack of immune system cells or impairment in differentiation of immune cells is the basis for many chronic diseases Metabolic changes could be the root cause for this immune cell impairment These changes could be a result of altered transcription, cytokine production from surrounding cells, and changes in metabolic pathways Immunity and mitochondria are interlinked with each other An important feature of mitochondria is it can regulate activation, differentiation, and survival of immune cells In addition, it can also release signals such as mitochondrial DNA (mtDNA) and mitochondrial ROS (mtROS) to regulate transcription of immune cells From current literature, we found that mitochondria can regulate immunity in different ways First, alterations in metabolic pathways (TCA cycle, oxidative phosphorylation, and FAO) and mitochondria induced transcriptional changes can lead to entirely different outcomes in immune cells For example, M1 macrophages exhibit a broken TCA cycle and have a pro-inflammatory role By contrast, M2 macrophages undergo β-oxidation to produce anti-inflammatory responses In addition, amino acid metabolism, especially arginine, glutamine, serine, glycine, and tryptophan, is critical for T cell differentiation and macrophage polarization Second, mitochondria can activate the inflammatory response For instance, mitochondrial antiviral signaling and NLRP3 can be activated by mitochondria Third, mitochondrial mass and mobility can be influenced by fission and fusion Fission and fusion can influence immune functions Finally, mitochondria are placed near the endoplasmic reticulum (ER) in immune cells Therefore, mitochondria and ER junction signaling can also influence immune cell metabolism Mitochondrial machinery such as metabolic pathways, amino acid metabolism, antioxidant systems, mitochondrial dynamics, mtDNA, mitophagy, and mtROS are crucial for immune functions Here, we have demonstrated how mitochondria coordinate to alter immune responses and how changes in mitochondrial machinery contribute to alterations in immune responses A better understanding of the molecular components of mitochondria is necessary This can help in the development of safe and effective immune therapy or prevention of chronic diseases In this review, we have presented an updated prospective of the mitochondrial machinery that drives various immune responses
TL;DR: Optimizing the prevention, recognition, and care of hypertension requires a paradigm shift to team-based care and the use of strategies known to control BP.
TL;DR: In this article, the authors performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals.
Abstract: C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10−8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.
TL;DR: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time to enable users to calculate temporal trends in biodiversity within and amongst assemblage using a broad range of metrics.
Abstract: Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km(2) (158 cm(2)) to 100 km(2) (1,000,000,000,000 cm(2)).Time period and grainBio: TIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.
TL;DR: Insomnia or poor sleep with PSG-short sleep was associated with higher risk of incident CVD, and future studies should evaluate the impact of interventions to improve insomnia with PSg- short sleep on CVD.
Abstract: Study Objectives To quantify the association between insomnia or poor sleep with objective short sleep duration and incident cardiovascular disease (CVD) and mortality in the general population. Methods We conducted a time-to-event analysis of Sleep Heart Health Study data. Questionnaires and at-home polysomnography (PSG) were performed between 1994 and 1998. Participants were followed for a median of 11.4 years (Q1-Q3, 8.8-12.4 years) until death or last contact. The primary exposure was insomnia or poor sleep with short sleep defined as follows: difficulty falling asleep, difficulty returning to sleep, early morning awakenings, or sleeping pill use, 16-30 nights per month; and total sleep of <6 hr on PSG. We used proportional hazard models to estimate the association between insomnia or poor sleep with short sleep and CVD, as well as all-cause mortality. Results Among 4994 participants (mean age: 64.0 ± 11.1 years), 14.1 per cent reported insomnia or poor sleep, of which 50.3 per cent slept <6 hr. Among 4437 CVD-free participants at baseline, we observed 818 incident CVD events. After propensity adjustment, there was a 29 per cent higher risk of incident CVD in the insomnia or poor sleep with short sleep group compared with the reference group (HR: 1.29, 95% CI: 1.00, 1.66), but neither the insomnia or poor sleep only nor short sleep only groups were associated with higher incident CVD. Insomnia or poor sleep with objective short sleep was not associated with all-cause mortality (HR: 1.07, 95% CI: 0.86, 1.33). Conclusions Insomnia or poor sleep with PSG-short sleep was associated with higher risk of incident CVD. Future studies should evaluate the impact of interventions to improve insomnia with PSG-short sleep on CVD.
TL;DR: A comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease are provided.
Abstract: The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease. © 2019 American Physiological Society. Compr Physiol 9:207-299, 2019.
Tulane University1, Ithaca College2, Brown University3, Washington University in St. Louis4, Comenius University in Bratislava5, Bloomsburg University of Pennsylvania6, University of Paris7, Yale University8, Slovak University of Technology in Bratislava9, University of Alabama10, Universidad de San Carlos de Guatemala11, University of Houston12
TL;DR: The findings indicate that this Lowland Maya society was a regionally interconnected network of densely populated and defended cities, which were sustained by an array of agricultural practices that optimized land productivity and the interactions between rural and urban communities.
Abstract: INTRODUCTION Lowland Maya civilization flourished from 1000 BCE to 1500 CE in and around the Yucatan Peninsula. Known for its sophistication in writing, art, architecture, astronomy, and mathematics, this civilization is still obscured by inaccessible forest, and many questions remain about its makeup. In 2016, the Pacunam Lidar Initiative (PLI) undertook the largest lidar survey to date of the Maya region, mapping 2144 km 2 of the Maya Biosphere Reserve in Guatemala. The PLI data have made it possible to characterize ancient settlement and infrastructure over an extensive, varied, and representative swath of the central Maya Lowlands. RATIONALE Scholars first applied modern lidar technology to the lowland Maya area in 2009, focusing analysis on the immediate surroundings of individual sites. The PLI covers twice the area of any previous survey and involves a consortium of scholars conducting collaborative and complementary analyses of the entire survey region. This cooperation among scholars has provided a unique regional perspective revealing substantial ancient population as well as complex previously unrecognized landscape modifications at a grand scale throughout the central lowlands in the Yucatan peninsula. RESULTS Analysis identified 61,480 ancient structures in the survey region, resulting in a density of 29 structures/km 2 . Controlling for a number of complex variables, we estimate an average density of ~80 to 120 persons/km 2 at the height of the Late Classic period (650 to 800 CE). Extrapolation of this settlement density to the entire 95,000 km 2 of the central lowlands produces a population range of 7 million to 11 million. Settlement distribution is not homogeneous, however; we found evidence of (i) rural areas with low overall density, (ii) periurban zones with small urban centers and dispersed populations, and (iii) urban zones where a single, large city integrated a wider population. The PLI survey revealed a landscape heavily modified for intensive agriculture, necessary to sustain populations on this scale. Lidar shows field systems in the low-lying wetlands and terraces in the upland areas. The scale of wetland systems and their association with dense populations suggest centralized planning, whereas upland terraces cluster around residences, implying local management. Analysis identified 362 km 2 of deliberately modified agricultural terrain and another 952 km 2 of unmodified uplands for potential swidden use. Approximately 106 km of causeways within and between sites constitute evidence of inter- and intracommunity connectivity. In contrast, sizable defensive features point to societal disconnection and large-scale conflict. CONCLUSION The 2144 km 2 of lidar data acquired by the PLI alter interpretations of the ancient Maya at a regional scale. An ancient population in the millions was unevenly distributed across the central lowlands, with varying degrees of urbanization. Agricultural systems found in lidar indicate how these populations were supported, although an irregular distribution suggests the existence of a regional agricultural economy of great complexity. Substantial infrastructural investment in integrative features (causeways) and conflictive features (defensive systems) highlights the interconnectivity of the ancient lowland Maya landscape. These perspectives on the ancient Maya generate new questions, refine targets for fieldwork, elicit regional study across continuous landscapes, and advance Maya archaeology into a bold era of research and exploration.
TL;DR: A voltage-dependent redox/double-layer co-charging behavior is found: the capacitive mechanism is dominated by the redox process, but the electric double-layer charge works against theredox process.
Abstract: MXenes have attracted great attention as next-generation capacitive energy-storage materials, but the mechanisms underlying their pseudocapacitive behavior are not well understood. Here we provide a theoretical description of the surface redox process of Ti3C2Tx (T = O, OH), a prototypical MXene, in 1 M H2SO4 electrolyte, based on joint density functional theory with an implicit solvation model and the analysis of Gibbs free energy under a constant-electrode potential. From the dependence of the O/OH ratio (or the surface H coverage) and the surface charge on the applied potential, we obtain a clear picture of the capacitive energy-storage mechanism of Ti3C2Tx that shows good agreement with previous experimental findings in terms of the integral capacitance and Ti valence change. We find a voltage-dependent redox/double-layer co-charging behavior: the capacitive mechanism is dominated by the redox process, but the electric double-layer charge works against the redox process. This new insight may be useful...
TL;DR: Based on the 2017 guideline, from 1999 to 2016, the age‐standardized prevalence of hypertension decreased and the proportion of control among those treated for hypertension improved, however, the absolute hypertension burden increased.
Abstract: Background Hypertension is a major risk factor for cardiovascular disease and all‐cause mortality. Compared with prior guidelines, the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline recommends lower blood pressure thresholds for defining hypertension, for initiating antihypertensive medication, and for antihypertensive medication treatment goals. Methods and Results To better understand potential impacts of the 2017 guideline, we studied trends in mean systolic blood pressure and diastolic blood pressure, prevalence and burden of hypertension, and proportion of controlled hypertension in the US adult population aged ≥20 from 1999 through 2016. We used data from 38 276 adults from the National Health and Nutrition Examination Survey. Age‐standardized prevalence of hypertension decreased from 48.4% in 1999–2000 to 45.4% in 2015–2016. However, absolute burden of hypertension consistently increased, from 87.0 million in 1999–2000 to 108.2 million in 2015–2016. The age‐standardized proportion of controlled hypertension among adults receiving antihypertensive pharmacologic treatment increased from 1999–2000 (25.6%) to 2015–2016 (43.5%). There was not consistent improvement in control throughout the full period among non‐Hispanic blacks, individuals aged ≥60, or those with diabetes mellitus, chronic kidney disease, or high cardiovascular disease risk. Conclusions Based on the 2017 guideline, from 1999 to 2016, the age‐standardized prevalence of hypertension decreased and the proportion of control among those treated for hypertension improved. However, the absolute hypertension burden increased. Among those treated, the control rate did not consistently improve in all subgroups. These data emphasize the need for continuous efforts in the prevention and control of hypertension in the US general population.
TL;DR: This review discusses the most fundamental gender differences in glucose homeostasis and diabetes, including the prevalence of impaired fasting glucose and impaired glucose tolerance, the prevalence and incidence of type 2 and type 1 diabetes, and the sex-specific effects of testosterone and estrogen deficiency and excess.
University of Kentucky1, University of Virginia2, University of Tsukuba3, University of California, Los Angeles4, Nagoya University5, Nagoya City University6, Icahn School of Medicine at Mount Sinai7, University of Southern California8, University of Colorado Denver9, University of California, Irvine10, Tulane University11, Kobe University12, Wakayama Medical University13, Texas A&M University14, University of Massachusetts Medical School15
TL;DR: It is demonstrated that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy, and an unexpected role of cGas in responding to mobile-element transcripts is highlighted.
Abstract: Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.
TL;DR: The findings implicate the potential utility of drug-repurposing as novel adjunct therapeutic strategies in advanced cancer.
Abstract: Targeting exosome biogenesis and release may have potential clinical implications for cancer therapy. Herein, we have optimized a quantitative high throughput screen (qHTS) assay to identify compounds that modulate exosome biogenesis and/or release by aggressive prostate cancer (PCa) CD63-GFP-expressing C4-2B cells. A total of 4,580 compounds were screened from the LOPAC library (a collection of 1,280 pharmacologically active compounds) and the NPC library (NCGC collection of 3,300 compounds approved for clinical use). Twenty-two compounds were found to be either potent activators or inhibitors of intracellular GFP signal in the CD63-GFP-expressing C4-2B cells. The activity of lead compounds in modulating the secretion of exosomes was validated by a tunable resistive pulse sensing (TRPS) system (qNano-IZON) and flow cytometry. The mechanism of action of the lead compounds in modulating exosome biogenesis and/or secretion were delineated by immunoblot analysis of protein markers of the endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways. The lead compounds tipifarnib, neticonazole, climbazole, ketoconazole, and triademenol were validated as potent inhibitors and sitafloxacin, forskolin, SB218795, fenoterol, nitrefazole and pentetrazol as activators of exosome biogenesis and/or secretion in PC cells. Our findings implicate the potential utility of drug-repurposing as novel adjunct therapeutic strategies in advanced cancer.
TL;DR: Closeout visits were completed to inquire whether BP measurements were usually attended or unattended by staff, and similar systolic and diastolic BPs within randomized groups were noted at the majority of visits in all 4 measurement categories.
Abstract: Recent publications have stated that the blood pressure (BP) measurement technique used in SPRINT (Systolic Blood Pressure Intervention Trial) was unattended. However, the SPRINT protocol does not address the issue of attendance. A survey was conducted immediately after SPRINT closeout visits were completed to inquire whether BP measurements were usually attended or unattended by staff. There were 4082 participants at 38 sites that measured BP after leaving the participant alone the entire time (always alone), 2247 at 25 sites that had personnel in the room the entire time (never alone), 1746 at 19 sites that left the participant alone only during the rest period (alone for rest), and 570 at 6 sites that left the participant alone only during the BP readings (alone for BP measurement). Similar systolic and diastolic BPs within randomized groups were noted during follow-up at the majority of visits in all 4 measurement categories. In the always alone and never alone categories, the intensive group had a similarly reduced risk for the primary outcome compared with the standard group (hazard ratio, 0.62; 95% confidence interval, 0.51–0.76 and hazard ratio, 0.64; 95% confidence interval, 0.46–0.91, respectively; pairwise interaction P value, 0.88); risk was not significantly reduced for the intensive group in the smaller alone-for-rest and the alone-for-BP-measurement categories. Similar BP levels and cardiovascular disease risk reduction were observed in the intensive group in SPRINT participants whether the measurement technique used was primarily attended or unattended. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.
09 Mar 2018
TL;DR: In this article, the authors demonstrate that density functional theory, with the recently developed strongly constrained and appropriately normed (SCAN) functional, has advanced to a point where both facets of the stability problem can be reliably and efficiently predicted for main group compounds, while transition metal compounds are improved but remain a challenge.
Abstract: The question of material stability is of fundamental importance to any analysis of system properties in condensed matter physics and materials science. The ability to evaluate chemical stability, i.e., whether a stoichiometry will persist in some chemical environment, and structure selection, i.e. what crystal structure a stoichiometry will adopt, is critical to the prediction of materials synthesis, reactivity and properties. Here, we demonstrate that density functional theory, with the recently developed strongly constrained and appropriately normed (SCAN) functional, has advanced to a point where both facets of the stability problem can be reliably and efficiently predicted for main group compounds, while transition metal compounds are improved but remain a challenge. SCAN therefore offers a robust model for a significant portion of the periodic table, presenting an opportunity for the development of novel materials and the study of fine phase transformations even in largely unexplored systems with little to no experimental data.