Hospital Variation In Admission To Intensive Care Units For Patients With Myocardial Infarction

The treatment of patients with myocardial infarction was transformed by the introduction of intensive care units (ICUs), but we know little about how contemporary hospitals employ this resource-intensive setting and whether higher use is associated with better outcomes. We sought to determine the variation in the rates of ICU admission across hospitals for patients with myocardial infarction and whether these rates were associated with mortality or usage of critical care therapies. We hypothesized that large variations exist in rates of ICU use for these patients across hospitals, but that these differences would not be associated with in-hospital mortality. We identified 114,980 adult hospitalizations for acute myocardial infarction from 311 hospitals in the 2009-10 Premier database using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. Hospitals were stratified into quartiles by rates of ICU admission for patients with myocardial infarction. Across quartiles, we examined in-hospital risk-standardized mortality rates and usage rates of critical care therapies for these patients. Rates of ICU admission for patients with myocardial infarction varied markedly among hospitals (median 48%, IQR 35%-61%, range 0%-98%) and there was no association with in-hospital risk-standardized mortality rates (6% all quartiles; p=0.7). However, hospitals admitting more patients to the ICU were more likely to use critical care therapies overall (mechanical ventilation [from Quartile 1 with lowest rate of ICU use to Quartile 4 with highest rate: 13% to 16%], vasopressors/inotropes [17% to 21%], intra-aortic balloon pumps [4% to 7%], and pulmonary artery catheters [4% to 5%]; p for trend\u3c0.05 in all comparisons). Rates of ICU admission for myocardial infarction vary substantially across hospitals and were not associated with differences in mortality, but were associated with greater use of critical care therapies

Association of Tenofovir Use With Risk of Incident Heart Failure in HIV-Infected Patients.

BackgroundThe antiretroviral medication, tenofovir disoproxil fumarate (TDF), is used by most human immunodeficiency virus-infected persons in the United States despite higher risks of chronic kidney disease. Although chronic kidney disease is a strong risk factor for heart failure (HF), the association of TDF with incident HF is unclear.Methods and resultsWe identified 21 435 human immunodeficiency virus-infected patients in the United States Veterans Health Administration actively using antiretrovirals between 2002 and 2011. We excluded patients with a prior diagnosis of HF. TDF was analyzed categorically (current, past, or never use) and continuously (per year of use). Proportional hazards regression and fully adjusted marginal structural models were used to determine the association of TDF exposure with risk of incident HF after adjustment for demographic, human immunodeficiency virus-related, and cardiovascular risk factors. During follow-up, 438 incident HF events occurred. Unadjusted 5-year event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7-1.1), 1.7 (1.4-2.2), and 4.5 (3.9-5.0), respectively. In fully adjusted analyses, HF risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53-0.86) compared with never users. Among current TDF users, each additional year of TDF exposure was associated with a 21% lower risk of incident HF (95%CI: 0.68-0.92). When limited to antiretroviral-naive patients, HF risk remained lower in current TDF users (HR=0.53; 95%CI 0.36-0.78) compared to never users.ConclusionsAmong a large national cohort of human immunodeficiency virus-infected patients, TDF use was strongly associated with lower risk of incident HF. These findings warrant confirmation in other populations, both with TDF and the recently approved tenofovir alafenamide fumarate

ABI4 Mediates Antagonistic Effects of Abscisic Acid and Gibberellins at Transcript and Protein Levels

Abscisic acid (ABA) and gibberellins (GA) are plant hormones which antagonistically mediate numerous physiological processes, and their optimal balance is essential for normal plant development. However, the molecular mechanism underlying ABA and GA antagonism still needs to be determined. Here, we report that ABA- INSENSITIVE 4 (ABI4) is a central factor for GA/ABA homeostasis and antagonism in post-germination stages. ABI4 over-expression in Arabidopsis (OE-ABI4) leads to developmental defects including a decrease in plant height and poor seed production. The transcription of a key ABA biosynthetic gene, NCED6, and of a key GA catabolic gene, GA2ox7, is significantly enhanced by ABI4 over-expression. ABI4 activates NCED6 and GA2ox7 transcription by directly binding to the promoters, and genetic analysis revealed that mutation in these two genes partially rescues the dwarf phenotype of ABI4 overexpressing plants. Consistently, ABI4 overexpressing seedlings have a lower GA/ABA ratio compared to the wild type. We further show that ABA induces GA2ox7 transcription while GA represses NCED6 expression in an ABI4-dependent manner; and that ABA stabilizes the ABI4 protein, whereas GA promotes its degradation. Taken together, these results propose that ABA and GA antagonize each other by oppositely acting on ABI4 transcript and protein levels

PTPRO-related CD8⁺ T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer

Background: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers. Methods: ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8+ T-cell signatures (PTSs). The Kaplan–Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets. Results: High PTPRO expression was related to high infiltration levels of CD8+ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8+ T cells in the TIME, we focused on the impact of PTPRO expression on CD8+ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs). Conclusion: PTPRO significantly impacts CD8+ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients

Regional Geological Survey of Hanggai, Xianxia and Chuancun, Zhejiang Province in China

This Open Access book introduces readers to the regional geology of Hanggai, Xianxia and Chuancun, the area between China's northern Zhejiang Province and southern Anhui Province and explores the strata, magmatic rocks and tectonic structures in 1:50,000 scale geological maps. Based on studies of multiple stratigraphic divisions, the standard stratigraphic section of the upper Ordovician Hirnantian in the lower Yangtze region is established, revealing for the first time numerous “Burgess Shale-type” sponge fossils in Hirnantian strata and identifying 10 grapholite fossil belts and various fossil categories, including chitin, trilobites, gastropods, brachiopods, and cephalopods. Moreover, the book identifies for the first time Late Ordovician volcanic events in northern Zhejiang province. The work represents a major contribution to research on Paleozoic strata in the Lower Yangtze region, and sheds new light on understanding the Hirnantian glacial event and biological extinction event in South China by providing a high-precision time scale. In addition, the book opens an important avenue for future research on sponge evolution after the Cambrian life explosion. As such, it offers a unique and valuable asset for researchers and graduate students alike

Integrated metabolomics and metagenomics analysis of plasma and urine identified microbial metabolites associated with coronary heart disease

Coronary heart disease (CHD) is top risk factor for health in modern society, causing high mortality rate each year. However, there is no reliable way for early diagnosis and prevention of CHD so far. So study the mechanism of CHD and development of novel biomarkers is urgently needed. In this study, metabolomics and metagenomics technology are applied to discover new biomarkers from plasma and urine of 59 CHD patients and 43 healthy controls and trace their origin. We identify GlcNAc-6-P which has good diagnostic capability and can be used as potential biomarkers for CHD, together with mannitol and 15 plasma cholines. These identified metabolites show significant correlations with clinical biochemical indexes. Meanwhile, GlcNAc-6-P and mannitol are potential metabolites originated from intestinal microbiota. Association analysis on species and function levels between intestinal microbes and metabolites suggest a close correlation between Clostridium sp. HGF2 and GlcNAc-6-P, Clostridium sp. HGF2, Streptococcus sp. M143, Streptococcus sp. M334 and mannitol. These suggest the metabolic abnormality is significant and gut microbiota dysbiosis happens in CHD patients

Progress in targeted observation for meso-scale convective system and some thoughts on its applications to convection nowcasting in large cities

Improving the forecasting skills of the meso-scale convective system (MCS) is one of the key scientific problems in the field of numerical weather prediction. The occurrence and development of severe convective weather are affected by multiple factors such as atmospheric thermodynamic and kinetic conditions, topography, and air pollution conditions. Due largely to the uncertainty in models and the inevitable errors of initial values, large uncertainties still exist for the accurate prediction of severe weather produced by the MCS. Therefore, to effectively improve the accuracy of severe convective weather forecasts in China, conducting targeted observation experiments in key areas of interest, which typically helps to reduce the uncertainty level of the model's initial meteorological field, may be one of the effective ways forward. It follows that the initiation and formation mechanisms of MCS can be revealed, and the forecast skills of severe convection will be improved. In this paper, we first propose the technology roadmap of targeted observation as follows. Based on the modern meteorological observational network over the Jing-Jin-Ji area, the typical MCS forecast sensitive regions are identified by using the Ensemble Transform Kalman filter, combined with the atmospheric sounding systems mounted on the mobile vehicle, where targeted observation experiments will be conducted. As such, convective initiation mechanisms are elucidated, and the novel methods expected to improve the forecast skill for MCS are explored. Secondly, in response to the challenge of "finding needles in a haystack" in the vertical observation of the lower atmosphere for short-term forecasting and warning of severe convective weather in large cities, the potential application value of a dynamic triangular observation mesonet in the study of triggering and development mechanisms of severe convective weather was explored through the construction of a Pyramid-shaped LOwer Tropospheric Observational System (PLOTOS) that consists of five stations with simultaneous vertical observation capabilities. Finally, it is suggested that the initiation and formation mechanisms of severe convective weather be unraveled using PLOTOS, and the mesoscale targeted observation technology be developed, which is crucial to the improvement of weather observational networks in large cities and provide new ideas and methods for improving the forecast of severe convective weather processes