This meta-analysis of both published and unpublished studies assesses factors believed to influence adoption of agricultural Best Management Practices in the United States. Using an established ...statistical technique to summarize the adoption literature in the United States, we identified the following variables as having the largest impact on adoption: access to and quality of information, financial capacity, and being connected to agency or local networks of farmers or watershed groups. This study shows that various approaches to data collection affect the results and comparability of adoption studies. In particular, environmental awareness and farmer attitudes have been inconsistently used and measured across the literature. This meta-analysis concludes with suggestions regarding the future direction of adoption studies, along with guidelines for how data should be presented to enhance the adoption of conservation practices and guide research.
► Provides a quantitative summary of the agricultural BMP literature. ► Information, financial, and networking variables have largest impact. ► Environmental awareness and farmer attitudes have been used inconsistently. ► Suggestions for future direction of the adoption literature.
Japan Stalker, Nancy K
2018., 20180814, 2018, 2018-08-14
eBook
Aesthetics and tradition occupy a central role in modern Japanese national identity to a degree seemingly unparalleled among the world's wealthiest nations. This text surveys highlights in Japanese ...history, culture, and society from prehistoric to contemporary times, devoting significant attention to the visual and literary arts and to everyday material culture in each period. It provides relatively equal coverage of the premodern and modern eras, describing important historical events, personages, and cultural developments. In addition, it traces gender ideals and the emergence of religious, intellectual, and social protest movements across time. Japan's twentieth century interlude as an empire and colonizer receives a full chapter of coverage, as do postwar economic growth and the nation's emergence as a cultural superpower in the twenty-first century. Countering general perceptions of Japan as a unique and isolated country, the text highlights how interactions with other civilizations, primarily Korea and China in premodern times and Western nations in modernity, have deeply influenced its politics, economy, society and resulted in cultural hybridity.
Essentials
Signaling by Gas6 through Tyro3/Axl/Mer receptors is essential for stable platelet aggregation.
UNC2025 is a small molecule inhibitor of the Mer tyrosine kinase.
UNC2025 decreases platelet ...activation in vitro and thrombus formation in vivo.
UNC2025's anti‐platelet effect is synergistic with inhibition of the ADP receptor, P2Y12.
Summary
Background
Growth arrest‐specific protein 6 signals through the TAM (TYRO‐3–AXL–MERTK) receptor family, mediating platelet activation and thrombus formation via activation of the aggregate‐stabilizing αIIbβ3 integrin.
Objective
To describe the antithrombotic effects mediated by UNC2025, a small‐molecule MERTK tyrosine kinase inhibitor.
Methods
MERTK phosphorylation and downstream signaling were assessed by immunoblotting. Light transmission aggregometry, flow cytometry and microfluidic analysis were used to evaluate the impact of MERTK inhibition on platelet activation and stability of aggregates in vitro. The effects of MERTK inhibition on arterial and venous thrombosis, platelet accumulation at microvascular injury sites and tail bleeding times were determined with murine models. The effects of combined treatment with ADP–P2Y1&12 pathway antagonists and UNC2025 were also evaluated.
Results and Conclusions
Treatment with UNC2025 inhibited MERTK phosphorylation and downstream activation of AKT and SRC, decreased platelet activation, and protected animals from pulmonary embolism and arterial thrombosis without increasing bleeding times. The antiplatelet effect of UNC2025 was enhanced in combination with ADP–P2Y1&12 pathway antagonists, and a greater than additive effect was observed when these two agents with different mechanisms of inhibition were coadministered. TAM kinase signaling represents a potential therapeutic target, as inhibition of this axis, especially in combination with ADP–P2Y pathway antagonism, mediates decreased platelet activation, aggregate stability, and thrombus formation, with less hemorrhagic potential than current treatment strategies. The data presented here also demonstrate antithrombotic activity mediated by UNC2025, a novel translational agent, and support the development of TAM kinase inhibitors for clinical applications.
OBJECTIVE—Rho-Kinase activity is increased in cardiovascular diseases and in patients with cardiovascular risk factors. However, it is not known whether inhibition of Rho-kinase could lead to ...cardiovascular protection and, if so, by what mechanism.
METHODS AND RESULTS—In human endothelial cells, the Rho-kinase inhibitor, hydroxyfasudil (HF) (1 to 100 μmol/L), increased Akt serine-473 phosphorylation within 15 minutes, leading to a 2.2-fold and 4.0-fold increase in Akt kinase activity and nitric oxide (NO) release, respectively. Activation of Akt and eNOS by HF was completely blocked by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, LY294002 (10 μmol/L). To determine the physiological relevance of this pathway, we used 2 models of ischemia-reperfusion (I/R) injury. Acute administration of fasudil (10 mg/kg, intraperitoneal, 1 hour before ischemia) decreased leukocyte recruitment and adhesion to the mesenteric endothelium after I/R injury in wild-type but not eNOS mice. Similarly, treatment with fasudil decreased myocardial infarct size by 38% in rats subjected to transient coronary artery occlusion. Cotreatment with 2 PI3-kinase inhibitors, wortmannin and LY294002, or the eNOS inhibitor, l-NAME, blocked the cardiovascular protective effects of fasudil.
CONCLUSIONS—Inhibition of Rho-kinase leads to the activation of the PI3-kinase/Akt/eNOS pathway and cardiovascular protection. These findings suggest that Rho-kinase may play an important role in mediating the inflammatory response to I/R injury.
Context:
Disorders of sex development (DSD) are clinical conditions where there is a discrepancy between the chromosomal sex and the phenotypic (gonadal or genital) sex of an individual. Such ...conditions can be stressful for patients and their families and have historically been difficult to diagnose, especially at the genetic level. In particular, for cases of 46,XY gonadal dysgenesis, once variants in SRY and NR5A1 have been ruled out, there are few other single gene tests available.
Objective:
We used exome sequencing followed by analysis with a list of all known human DSD-associated genes to investigate the underlying genetic etiology of 46,XY DSD patients who had not previously received a genetic diagnosis.
Design:
Samples were either submitted to the research laboratory or submitted as clinical samples to the UCLA Clinical Genomic Center. Sequencing data were filtered using a list of genes known to be involved in DSD.
Results:
We were able to identify a likely genetic diagnosis in more than a third of cases, including 22.5% with a pathogenic finding, an additional 12.5% with likely pathogenic findings, and 15% with variants of unknown clinical significance.
Conclusions:
Early identification of the genetic cause of a DSD will in many cases streamline and direct the clinical management of the patient, with more focused endocrine and imaging studies and better-informed surgical decisions. Exome sequencing proved an efficient method toward such a goal in 46,XY DSD patients.
An optimal platelet response to injury can be defined as one in which blood loss is restrained and haemostasis is achieved without the penalty of further tissue damage caused by unwarranted vascular ...occlusion. This brief review considers some of the ways in which thrombus growth and stability can be regulated so that an optimal platelet response can be achieved in vivo. Three related topics are considered. The first focuses on intracellular mechanisms that regulate the early events of platelet activation downstream of G protein coupled receptors for agonists such as thrombin, thromboxane A2 and ADP. The second considers the ways in which signalling events that are dependent on stable contacts between platelets can influence the state of platelet activation and thus affect thrombus growth and stability. The third focuses on the changes that are experienced by platelets as they move from their normal environment in freely‐flowing plasma to a very different environment within the growing haemostatic plug, an environment in which the narrowing gaps and junctions between platelets not only facilitate communication, but also increasingly limit both the penetration of plasma and the exodus of platelet‐derived bioactive molecules.
Recent proof tests have shown that the annular core research reactor (ACRR) fuel motion detection system has reached its design goals of providing high temporal and spatial resolution pictures of ...fuel distributions in the ACRR. The coded aperture imaging system (CAIS) images the fuel by monitoring the fission gamma rays from the fuel that pass through collimators in the reactor core. The gamma-ray beam is modulated by coded apertures before producing a visible light coded image in thin scintillators. Each coded image is then amplified and recorded by an optical-image-intensifier/fast-framing-camera combination. The proximity to the core and the coded aperture technique provide a high data collection rate and high resolution.
Experiments of CAIS at the ACRR conducted under steady-state operation have documented the beneficial effects of changes in the radiation shielding and imaging technique. The spatial resolutions are 1.7 mm perpendicular to the axis of a single liquid-metal fast breeder reactor fuel pin and 9 mm in the axial dimension. Changes in mass of 100 mg in each resolution element can be detected each frame period, which may be from 5 to 100 ms. This diagnostic instrument may help resolve important questions in fuel motion phenomenology.
Aims: To determine the pharmacokinetics and tolerance of oral and intravenous linezolid, an oxazolidinone antibiotic, in healthy volunteers following single- and multiple-dose administration. ...Methods: In two randomized, double-blind, placebo-controlled, dose-escalating trials, subjects were exposed either to oral (375, 500 or 625 mg) or intravenous (500 or 625 mg) linezolid or placebo twice daily. Serial blood and urine samples were obtained after the first- and multiple-dose administrations for up to 18 days. Non-compartmental pharmacokinetic analyses were used to describe the disposition of linezolid. Results: Plasma linezolid concentrations and area under the concentration–time curves increased proportionally with dose irrespective of the route of administration. Plasma linezolid concentrations remained above the MIC90 for susceptible target pathogens (4.0 mg/L) for the majority of the 12 h dosing interval. Mean clearance, half-life and volume of distribution were similar irrespective of dose for both the oral and intravenous routes. Linezolid was well tolerated and the frequency of drug-related adverse events was similar between the linezolid and placebo groups. Conclusions: Oral and intravenous linezolid exhibit linear pharmacokinetics, with concentrations remaining above the target MIC90 for most of the dosing interval. These results support a twice-daily schedule for linezolid and demonstrate the feasibility of converting from intravenous to oral dosing without a dose adjustment.
PDF
