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The amazing Spider-Man
The family of one of Spider-Man's greatest foes is wreaking havoc across the universe.
BOOK
MetPy
MetPy is an open-source, Python-based package for meteorology, providing domain-specific functionality built extensively on top of the robust scientific Python software stack, which includes libraries like NumPy, SciPy, Matplotlib, and xarray. The goal of the project is to bring the weather analysis capabilities of GEMPAK (and similar software tools) into a modern computing paradigm. MetPy strives to employ best practices in its development, including software tests, continuous integration, and automated publishing of web-based documentation. As such, MetPy represents a sustainable, long-term project that fills a need for the meteorological community. MetPy’s development is substantially driven by its user community, both through feedback on a variety of open, public forums like Stack Overflow, and through code contributions facilitated by the GitHub collaborative software development platform. MetPy has recently seen the release of version 1.0, with robust functionality for analyzing and visualizing meteorological datasets. While previous versions of MetPy have already seen extensive use, the 1.0 release represents a significant milestone in terms of completeness and a commitment to long-term support for the programming interfaces. This article provides an overview of MetPy’s suite of capabilities, including its use of labeled arrays and physical unit information as its core data model, unit-aware calculations, cross sections, skew T and GEMPAK-like plotting, station model plots, and support for parsing a variety of meteorological data formats. The general road map for future planned development for MetPy is also discussed.
Journal Article
The Flash
\"When Wally West, the adolescent nephew of the Flash's fiancee accidentally gained powers of superspeed, he became the Scarlet Speedster's sidekick. Growing up as his hero's protege, Kid Flash had a childhood of amazing action and adventure. But on the day that The Flash died, Wally's carefree adolescence abruptly ended and his life as an adult began. THE FLASH BY MARK WAID BOOK ONE looks back at Wally's earliest days as the Kid Flash and explores the gamut of his emotions and experiences from his first day as a child hero to his succession of Barry Allen as the new Flash. A journey full of humor and drama, this story shows just how much Wally West loves being the fastest man alive\"-- Provided by publisher.
Book
Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy
In a prospective study involving women with epilepsy, the incidence of seizures was similar regardless of whether women were pregnant or not pregnant during similar time periods. Pregnant women had more changes in the dose of anticonvulsant drugs during pregnancy than did nonpregnant women.
Journal Article
Bone-Density Testing Interval and Transition to Osteoporosis in Older Women
This study analyzed the transition from normal BMD or osteopenia to osteoporosis; in women 67 years of age or older, the time for 10% to develop osteoporosis was approximately 15 years for normal BMD or mild osteopenia at baseline, 5 years for moderate osteopenia, and 1 year for advanced osteopenia.
Current osteoporosis management guidelines
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recommend routine bone mineral density (BMD) screening with the use of dual-energy x-ray absorptiometry (DXA) scans for women 65 years of age or older, but no guidelines specify an osteoporosis screening interval that is based on data from longitudinal cohort studies. The U.S. Preventive Services Task Force stated in 2011, “Because of limitations in the precision of testing, a minimum of 2 years may be needed to reliably measure a change in BMD; however, longer intervals may be necessary to improve fracture risk prediction.”
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To our knowledge, no U.S. study has addressed this clinical uncertainty. . . .
Journal Article
Evaluating the promise of recombinant transmissible vaccines
•Transmissible vaccines can spread between hosts, increasing vaccination efficiency.•Recombinant transmissible vaccines (RTVs) are built from a vector virus and pathogen antigen.•If the vector is endemic, cross-immunity between the vector and vaccine hampers vaccine spread.•Vector-vaccine competition displaces vaccine unless supplemented with manual vaccination.•RTVs enhance effectiveness of vaccination programs if supplemented with manual vaccinations.
Transmissible vaccines have the potential to revolutionize infectious disease control by reducing the vaccination effort required to protect a population against a disease. Recent efforts to develop transmissible vaccines focus on recombinant transmissible vaccine designs (RTVs) because they pose reduced risk if intra-host evolution causes the vaccine to revert to its vector form. However, the shared antigenicity of the vaccine and vector may confer vaccine-immunity to hosts infected with the vector, thwarting the ability of the vaccine to spread through the population. We build a mathematical model to test whether a RTV can facilitate disease management in instances where reversion is likely to introduce the vector into the population or when the vector organism is already established in the host population, and the vector and vaccine share perfect cross-immunity. Our results show that a RTV can autonomously eradicate a pathogen, or protect a population from pathogen invasion, when cross-immunity between vaccine and vector is absent. If cross-immunity between vaccine and vector exists, however, our results show that a RTV can substantially reduce the vaccination effort necessary to control or eradicate a pathogen only when continuously augmented with direct manual vaccination. These results demonstrate that estimating the extent of cross-immunity between vector and vaccine is a critical step in RTV design, and that herpesvirus vectors showing facile reinfection and weak cross-immunity are promising.
Journal Article
Controlling epidemics with transmissible vaccines
As the density of human and domestic animal populations increases, the threat of localized epidemics and global pandemics grows. Although effective vaccines have been developed for a number of threatening pathogens, manufacturing and disseminating vaccines in the face of a rapidly spreading epidemic or pandemic remains a formidable challenge. One potentially powerful solution to this problem is the use of transmissible vaccines. Transmissible vaccines are capable of spreading from one individual to another and are currently being developed for a range of infectious diseases. Here we develop and analyze mathematical models that allow us to quantify the benefits of vaccine transmission in the face of an imminent or ongoing epidemic. Our results demonstrate that even a small amount of vaccine transmission can greatly increase the rate at which a naïve host population can be protected against an anticipated epidemic and substantially reduce the size of unanticipated epidemics if vaccination is initiated shortly after pathogen detection. In addition, our results identify key biological properties and implementation practices that maximize the impact of vaccine transmission on infectious disease.
Journal Article
A phase I safety and immunogenicity dose escalation trial of plague vaccine, Flagellin/F1/V, in healthy adult volunteers (DMID 08-0066)
Intentional aerosolization of Yersinia pestis may result in pneumonic plague which is highly fatal if not treated early.
We conducted a phase 1 randomized, double blind (within each group), placebo controlled, dose escalation trial to evaluate a plague vaccine, Flagellin/F1/V, in healthy adults aged 8 through 45years. Vaccine was administered intramuscularly on Days 0 and 28 at a dose of 1, 3, 6 or 10mcg. Subjects were observed for 4h after vaccination for cytokine release syndrome. Reactogenicity and adverse events (AE) were collected for 14 and 28days, respectively, after each vaccination. Serious AE were collected for the entire study. ELISA antibody and cytokines were measured at multiple time points. Subject’s participation lasted 13months.
Sixty healthy subjects were enrolled; 52% males, 100% non-Hispanic, 91.7% white and mean age 30.8years. No severe reactogenicity events occurred; most AE were mild. No serious AE related to vaccine occurred. A dose response effect was observed to F1, V and flagellin. The peak ELISA IgG antibody titers (95% CI) after two 10mcg doses of vaccine were 260.0 (102.6–659.0) and 983.6 (317.3–3048.8), respectively, against F1 and V antigens. The 6mcg dose group provided similar titers. Titers were low for the placebo, 1mcg and 3mcg recipients. A positive antibody dose response was observed to F1, V and flagellin. Vaccine antigen specific serum IgE was not detected. There were no significant rises in serum or cellular cytokine responses and no significant IgG increase to flagellin after the second dose.
The Flagellin/F1/V vaccine exhibited a dose dependent increase in immunogenicity and was well tolerated at all doses. Antibody specific responses to F1, V and flagellin increased as dose increased. Given the results from this trial, testing higher doses of the vaccine may be merited.
Journal Article
Association of Coagulation Activation with Clinical Complications in Sickle Cell Disease
The contribution of hypercoagulability to the pathophysiology of sickle cell disease (SCD) remains poorly defined. We sought to evaluate the association of markers of coagulation and platelet activation with specific clinical complications and laboratory variables in patients with SCD.
Plasma markers of coagulation activation (D-dimer and TAT), platelet activation (soluble CD40 ligand), microparticle-associated tissue factor (MPTF) procoagulant activity and other laboratory variables were obtained in a cohort of patients with SCD. Tricuspid regurgitant jet velocity was determined by Doppler echocardiography and the presence/history of clinical complications was ascertained at the time of evaluation, combined with a detailed review of the medical records.
No significant differences in the levels of D-dimer, TAT, soluble CD40 ligand, and MPTF procoagulant activity were observed between patients in the SS/SD/Sβ⁰ thalassemia and SC/Sβ+ thalassemia groups. Both TAT and D-dimer were significantly correlated with measures of hemolysis (lactate dehydrogenase, indirect bilirubin and hemoglobin) and soluble vascular cell adhesion molecule-1. In patients in the SS/SD/Sβ⁰ thalassemia group, D-dimer was associated with a history of stroke (p = 0.049), TAT was associated with a history of retinopathy (p = 0.0176), and CD40 ligand was associated with the frequency of pain episodes (p = 0.039). In multivariate analyses, D-dimer was associated with reticulocyte count, lactate dehydrogenase, NT-proBNP and history of stroke; soluble CD40 ligand was associated with WBC count and platelet count; and MPTF procoagulant activity was associated with hemoglobin and history of acute chest syndrome.
This study supports the association of coagulation activation with hemolysis in SCD. The association of D-dimer with a history of stroke suggests that coagulation activation may contribute to the pathophysiology of stroke in clinically severe forms of SCD. More research is needed to evaluate the contribution of coagulation and platelet activation to clinical complications in SCD.
Journal Article
Phase 1 testing of detoxified LPS/group B meningococcal outer membrane protein vaccine with and without synthetic CPG 7909 adjuvant for the prevention and treatment of sepsis
•A vaccine elicits antibodies against a highly conserved core region of GNB endotoxin.•This detoxified endotoxin vaccine with and without two different doses of CPG 7909 adjuvant was given to healthy subjects.•The adverse effects of those given vaccine+CPG 7909, vaccine alone or placebo were similar.•Addition of CPG 7909 appeared to increase and accelerate the IgG and IgM antibody responses to the core glycolipid.•This vaccine merits further investigation as an adjunct to therapy against GNB infections.
Gram-negative bacteria (GNB) are a leading cause of nosocomial infection and sepsis. Increasing multi-antibiotic resistance has left clinicians with fewer therapeutic options. Antibodies to GNB lipopolysaccharide (LPS, or endotoxin) have reduced morbidity and mortality as a result of infection and are not subject to the resistance mechanisms deployed by bacteria against antibiotics. In this phase 1 study, we administered a vaccine that elicits antibodies against a highly conserved portion of LPS with and without a CpG oligodeoxynucleotide (ODN) TLR9 agonist as adjuvant.
A vaccine composed of the detoxified LPS (dLPS) from E. coli O111:B4 (J5 mutant) non-covalently complexed to group B meningococcal outer membrane protein (OMP). Twenty healthy adult subjects received three doses at 0, 29 and 59 days of antigen (10μg dLPS) with or without CPG 7909 (250 or 500μg). Subjects were evaluated for local and systemic adverse effects and laboratory findings. Anti-J5 LPS IgG and IgM antibody levels were measured by electrochemiluminesence. Due to premature study termination, not all subjects received all three doses.
All vaccine formulations were well-tolerated with no local or systemic events of greater than moderate severity. The vaccine alone group achieved a ≥4-fold “responder” response in IgG and IgM antibody in only one of 6 subjects. In contrast, the vaccine plus CPG 7909 groups appeared to have earlier and more sustained (to 180 days) responses, greater mean-fold increases, and a higher proportion of “responders” achieving ≥4-fold increases over baseline.
Although the study was halted before all enrolled subjects received all three doses, the J5dLPS/OMP vaccine, with or without CpG adjuvant, was safe and well-tolerated. The inclusion of CpG increased the number of subjects with a ≥4-fold antibody response, evident even after the second of three planned doses. A vaccine comprising J5dLPS/OMP antigen with CpG adjuvant merits further investigation.
ClinicalTrials.gov Identifier: NCT01164514.
Journal Article