Comparison of the Anticoagulant Response of a Novel Fluorogenic Anti-FXa Assay wth Two Commercial Anti-FXa Chromogenic Assays

Introduction: Fast and accurate monitoring is crucial in the successful regulation of coagulation therapy. For the treatment of venous thromboembolism, both unfractionated heparin (UFH) and low molecular weight heparins (LMWH) are commonly administered. The chromogenic anti-factor Xa (FXa) assay is currently considered the ‘gold standard’ assay for monitoring LMWH. However different commercial chromogenic methods often differ when tested with the same samples. Fluorogenic anti-FXa assays have the potential to offer greater benefits over chromogenic assays in terms of greater specificity, sensitivity and they are not so influenced by sample opacity or turbidity. Materials and Methods: Commercial plasmas were spiked with pharmacologically relevant concentrations (0–1 U/ml) of UFH, enoxaparin, and tinzaparin. The fluorogenic assay was carried out using previously optimized concentrations of 4 nM FXa and 0.9 μM fluorogenic substrate, in addition to 6.25 μl of 100 mM CaCl2 and 43.75 μl of plasma. The Biophen® and Coamatic chromogenic assays were carried out according to the manufacturer’s instructions. Reaction rates and endpoint values were analyzed and statistical analysis by means of one-way analysis of variance (ANOVA) was performed. Results: The fluorogenic anti-FXa assay was found to have the broadest therapeutic range of 0-1 U/ml with CVs of \u3c 5% for UFH and tinzaparin and CVs \u3c 9% for enoxaparin. Despite their limited measuring range, excellent reproducibility was observed with both chromogenic assays Conclusions: This study indicated that the fluorogenic assay is the most sensitive assay with the broadest dynamic range for monitoring LMWH therapy when compared with standard chromogenic assays

Young, American Indian or Alaskan Native, and born in the USA: at excess risk of starting extra-medical prescription pain reliever use?

Background Prescription pain reliever (PPR) overdoses differentially affect ‘American Indian/Alaskan Natives’ in the United States (US). Here, studying onset of extra-medical PPR use in 12-24-year-olds, we examine subgroup variations in rates of starting to use prescription pain relievers extra-medically (i.e., to get ‘high’ or for other reasons outside boundaries of prescriber’s intent). Risk differences (RD) are estimated for US-born versus non-US-born young people, stratified by American Indian/Alaskan Natives versus other ethnic self-identities. Methods Between 2002–2009, nationally representative cross-sectional samples of 12–24-year-old non-institutionalized civilians completed interviews for the US National Surveys of Drug Use and Health. Analysis-weighted annual incidence estimates, RD, and confidence intervals (CI) are from the Restricted-use Data Analysis System, an online software tool for US National Surveys of Drug Use and Health. Results Each year, an estimated 2.5% of 12-24-year-olds in the US start using PPR extra-medically (95% CI [2.1%–3.0%]). Estimates for the US-born (3.8%; 95% CI [3.7%–3.9%]) are larger (non-US-born: 1.8%; 95% CI [1.5%–2.0%]; RD = 2.0; p < 0.05). US-born American Indian/Alaskan Natives youths have the largest incidence rate (4.8%). Robust RD for US-born can be seen for ‘non-Hispanic White’ subgroups, and for others (e.g., ‘Cuban’, ‘Dominican’). Discussion Each year, one in 20 of US-born American Indian/Alaskan Natives starts using PPR extra-medically. Overdose prevention is important, but is no substitute for primary prevention initiatives for all young people. The observed epidemiological patterns can guide targeted prevention initiatives for the identified higher risk subgroups in complement with more universal prevention efforts intended to reduce incidence of first extra-medical PPR use, a crucial rate-limiting step on the path toward more serious drug involvement (i.e., progressing past initial use)

Rethinking the “Diseases of Affluence” Paradigm: Global Patterns of Nutritional Risks in Relation to Economic Development

BACKGROUND: Cardiovascular diseases and their nutritional risk factors—including overweight and obesity, elevated blood pressure, and cholesterol—are among the leading causes of global mortality and morbidity, and have been predicted to rise with economic development. METHODS AND FINDINGS: We examined age-standardized mean population levels of body mass index (BMI), systolic blood pressure, and total cholesterol in relation to national income, food share of household expenditure, and urbanization in a cross-country analysis. Data were from a total of over 100 countries and were obtained from systematic reviews of published literature, and from national and international health agencies. BMI and cholesterol increased rapidly in relation to national income, then flattened, and eventually declined. BMI increased most rapidly until an income of about I$5,000 (international dollars) and peaked at about I$12,500 for females and I$17,000 for males. Cholesterol's point of inflection and peak were at higher income levels than those of BMI (about I$8,000 and I$18,000, respectively). There was an inverse relationship between BMI/cholesterol and the food share of household expenditure, and a positive relationship with proportion of population in urban areas. Mean population blood pressure was not correlated or only weakly correlated with the economic factors considered, or with cholesterol and BMI. CONCLUSIONS: When considered together with evidence on shifts in income–risk relationships within developed countries, the results indicate that cardiovascular disease risks are expected to systematically shift to low-income and middle-income countries and, together with the persistent burden of infectious diseases, further increase global health inequalities. Preventing obesity should be a priority from early stages of economic development, accompanied by population-level and personal interventions for blood pressure and cholesterol

Episodic Accretion in Protostars -- An ALMA Survey of Molecular Jets in the Orion Molecular Cloud

Protostellar outflows and jets are almost ubiquitous characteristics during the mass accretion phase, and encode the history of stellar accretion, complex-organic molecule (COM) formation, and planet formation. Episodic jets are likely connected to episodic accretion through the disk. Despite the importance, there is a lack of studies of a statistically significant sample of protostars via high-sensitivity and high-resolution observations. To explore episodic accretion mechanisms and the chronologies of episodic events, we investigated 42 fields containing protostars with ALMA observations of CO, SiO, and 1.3\,mm continuum emission. We detected SiO emission in 21 fields, where 19 sources are driving confirmed molecular jets with high abundances of SiO. Jet velocities, mass-loss rates, mass-accretion rates, and periods of accretion events are found to be dependent on the driving forces of the jet (e.g., bolometric luminosity, envelope mass). Next, velocities and mass-loss rates are positively correlated with the surrounding envelope mass, suggesting that the presence of high mass around protostars increases the ejection-accretion activity. We determine mean periods of ejection events of 20$-$175 years for our sample, which could be associated with perturbation zones of $\sim$ 2$-$25\,au extent around the protostars. Also, mean ejection periods are anti-correlated with the envelope mass, where high-accretion rates may trigger more frequent ejection events. The observed periods of outburst/ejection are much shorter than the freeze-out time scale of the simplest COMs like CH$_3$OH, suggesting that episodic events largely maintain the ice-gas balance inside and around the snowline.Comment: Submitted to Journal; 27 pages, 15 Figures and additional Appendix materia

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Quinta-Gamelin Community Center: Architectural Design

The new facility will add meeting space for many of community organizations and sport leagues as well as people interested in renting the gymnasium and meeting rooms. Last year our community center gymnasium was given out 192 times on an average of two hours each, our meeting room was given out 68 times. Similar towns rent these facilities at approximately $15.00 an hour

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI