Abstract
Utilizing transaction-level financial data, we explore how household consumption responded to the onset of the COVID-19 pandemic. As case numbers grew and cities and states enacted ...shelter-in-place orders, Americans began to radically alter their typical spending across a number of major categories. In the first half of March 2020, individuals increased total spending by over 40% across a wide range of categories. This was followed by a decrease in overall spending of 25%–30% during the second half of March coinciding with the disease spreading, with only food delivery and grocery spending as major exceptions to the decline. Spending responded most strongly in states with active shelter-in-place orders, though individuals in all states had sizable responses. We find few differences across individuals with differing political beliefs, but households with children or low levels of liquidity saw the largest declines in spending during the latter part of March.
Job search is a key choice variable in theories of labor markets but is difficult to measure directly. We develop a job search activity index based on Google search data, the Google Job Search Index ...(GJSI). We validate the GJSI with both survey- and web-based measures of job search. Unlike those measures, the GJSI is high frequency, geographically precise, and available in real time. We demonstrate the GJSI’s utility by using it to study the effects of unemployment insurance policy changes between 2008 and 2014. We find no evidence of an economically meaningful effect of these changes on aggregate search.
Background. Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection ...(ARI). Methods. A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. Results. In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4–12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7–$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. Conclusions. The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.
Leveraging -omics for asthma endotyping Tyler, Scott R.; Bunyavanich, Supinda
Journal of allergy and clinical immunology,
July 2019, 2019-07-00, 20190701, Letnik:
144, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Asthma is a highly heterogeneous disease, often manifesting with wheeze, dyspnea, chest tightness, and cough as prominent symptoms. The eliciting factors, natural history, underlying molecular ...biology, and clinical management of asthma vary highly among affected subjects. Because of this variation, many efforts have gone into subtyping asthma. Endotypes are subtypes of disease based on distinct pathophysiologic mechanisms. Endotypes can be clinically useful because they organize our mechanistic understanding of heterogeneous diseases and can direct treatment toward modalities that are likely to be the most effective. Asthma endotyping can be shaped by clinical features, laboratory parameters, and/or -omics approaches. We discuss the application of -omics approaches, including transcriptomics, epigenomics, microbiomics, metabolomics, and proteomics, to asthma endotyping. -Omics approaches have provided supporting evidence for many existing endotyping paradigms and also suggested novel ways to conceptualize asthma endotypes. Although endotypes based on single -omics approaches are relatively common, their integrated multi-omics application to asthma endotyping has been more limited thus far. We discuss paths forward to integrate multi-omics with clinical features and laboratory parameters to achieve the goal of precise asthma endotypes.
CREB-mediated transcription can be initiated by membrane receptor stimulation and subsequent activation of intracellular pathways to the cell nucleus, and has been described as a molecular switch ...required for learning and memory. While CREB dimers are thought to be constitutively bound to response elements on DNA under basal conditions, it is CREB phosphorylation that is believed to be responsible for transcriptional activation leading to gene products such as BDNF that play a key role in synaptic plasticity and cognitive function. Conversely, preclinical and clinical findings now suggest that impaired CREB phosphorylation may be a pathological component in neurodegenerative disorders, in particular Alzheimer's disease (AD). In this regard, pharmacological-induced CREB phosphorylation in brain regions associated with cognition, i.e. cortex and hippocampus may represent a mechanistic basis for the development of novel AD therapeutics. The purpose of this commentary is to describe an experimental strategy to biochemically characterize the pharmacological induction of CREB phosphorylation as a mechanistic marker across different pharmacological classes of compounds for the potential treatment of AD that include: α7 nicotinic agonists, H3 antagonists and 11β HSD1 inhibitors.
Understanding and reversing the widespread population declines of birds require estimating the magnitude of all mortality sources. Numerous anthropogenic mortality sources directly kill birds. ...Cause-specific annual mortality in the United States varies from billions (cat predation) to hundreds of millions (building and automobile collisions), tens of millions (power line collisions), millions (power line electrocutions, communication tower collisions), and hundreds of thousands (wind turbine collisions). However, great uncertainty exists about the independent and cumulative impacts of this mortality on avian populations. To facilitate this understanding, additional research is needed to estimate mortality for individual bird species and affected populations, to sample mortality throughout the annual cycle to inform full life-cycle population models, and to develop models that clarify the degree to which multiple mortality sources are additive or compensatory. We review sources of direct anthropogenic mortality in relation to the fundamental ecological objective of disentangling how mortality sources affect animal populations.
Aesthetic experience has had a long and contentious history in the Western intellectual tradition. Following Kant and Hegel, a human’s interaction with nature or art frequently has been ...conceptualized as separate from issues of practical activity or moral value. This book examines how art can be seen as a way of moral cultivation. Scott Stroud uses the thought of the American pragmatist John Dewey to argue that art and the aesthetic have a close connection to morality. Dewey gives us a way to reconceptualize our ideas of ends, means, and experience so as to locate the moral value of aesthetic experience in the experience of absorption itself, as well as in the experience of reflective attention evoked by an art object.
Pinometostat (EPZ-5676) is a first-in-class small-molecule inhibitor of the histone methyltransferase disrupter of telomeric silencing 1-like (DOT1L). In this phase 1 study, pinometostat was ...evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving mixed lineage leukemia (MLL) gene rearrangements (MLL-r) resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose-escalation cohorts (n = 26) and 2 expansion cohorts (n = 25) at pinometostat doses of 54 and 90 mg/m2 per day by continuous intravenous infusion in 28-day cycles. Because a maximum tolerated dose was not established in the dose-escalation phase, the expansion doses were selected based on safety and clinical response data combined with pharmacodynamic evidence of reduction in H3K79 methylation during dose escalation. Across all dose levels, plasma pinometostat concentrations increased in an approximately dose-proportional fashion, reaching an apparent steady-state by 4-8 hours after infusion, and rapidly decreased following treatment cessation. The most common adverse events, of any cause, were fatigue (39%), nausea (39%), constipation (35%), and febrile neutropenia (35%). Overall, 2 patients, both with t(11;19), experienced complete remission at 54 mg/m2 per day by continuous intravenous infusion, demonstrating proof of concept for delivering clinically meaningful responses through targeting DOT1L using the single agent pinometostat in MLL-r leukemia patients. Administration of pinometostat was generally safe, with the maximum tolerated dose not being reached, although efficacy as a single agent was modest. This study demonstrates the therapeutic potential for targeting DOT1L in MLL-r leukemia and lays the groundwork for future combination approaches in this patient population. This clinical trial is registered at www.clinicaltrials.gov as NCT01684150.
•Pinometostat demonstrates first evidence of DOT1L target inhibition and clinical responses in a subset of MLL-r advanced leukemia patients.•The observed safety profile of pinometostat shows potential for exploration of combination therapies in leukemia.
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Anthropogenic threats, such as collisions with man-made structures, vehicles, poisoning and predation by domestic pets, combine to kill billions of wildlife annually. Free-ranging domestic cats have ...been introduced globally and have contributed to multiple wildlife extinctions on islands. The magnitude of mortality they cause in mainland areas remains speculative, with large-scale estimates based on non-systematic analyses and little consideration of scientific data. Here we conduct a systematic review and quantitatively estimate mortality caused by cats in the United States. We estimate that free-ranging domestic cats kill 1.4-3.7 billion birds and 6.9-20.7 billion mammals annually. Un-owned cats, as opposed to owned pets, cause the majority of this mortality. Our findings suggest that free-ranging cats cause substantially greater wildlife mortality than previously thought and are likely the single greatest source of anthropogenic mortality for US birds and mammals. Scientifically sound conservation and policy intervention is needed to reduce this impact.
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