1,315 research outputs found

    Calcein Inhibits Vesicle Release

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    Development and testing of a multidimensional parent reported outcome measure for common presenting complaints of infancy: the UK infant questionnaire.

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    Objectives: Patient reported outcome measures are recognized as important and valuable tools to monitor patient progress in healthcare. It is fundamental to clinical practice to understand whether the treated patient has improved or not. Despite the highest use of outpatient healthcare among all pediatric age groups, no age-appropriate outcome measures are available for the infant. Therefore, the objective of this study was to develop and test a new infant outcomes instrument for the most common presenting complaints of infancy. Methods: This was a multi-phase study designed to develop a questionnaire using maternal interviews and to test it for reliability and validity for use in well child clinical practice. After collecting the mother’s views, grounded theory and content analysis were used to derive themes and domains for the questionnaire. After achieving face validity, the instrument was evaluated for test-retest reliability, homogeneity and concurrent criterion validity. Subjects comprised a convenience sample of mothers who presented their infants to a university-affiliated chiropractic teaching clinic on the south coast of England. Results: Maternal interviews revealed mothers’ concerns about feeding, sleeping, crying and other aspects of infant activities of daily living resulting in construction of a 12 question instrument. The questionnaire showed excellent test-retest reliability (ICC = 0.96) and good internal consistency (Cronbach’s α = 0.8). In validity testing, ten questions showed positive correlation to a statistically significant degree against their established gold standard references. In all, 294 mother/infant dyads were involved in the research project. Conclusion: The UK Infant Questionnaire is the first parent reported outcome measure for use with the most common complaints of the infant patient based on maternal views. As such, this instrument meets the standard set by the UK National Health Service to involve the parent’s voice in their child’s care, and is therefore innovative in its field. Although further testing is indicated, and we make no claims that this instrument is comprehensive in all aspects of infant well-child care, it may be used by individual clinicians in routine daily practice to gain understanding of clinical progress of individual patients

    All-Payer Claims Databases: An Overview for Policymakers

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    Long Term Care Insurance Beyond the CLASS Program

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    The Community Living Assistance and Supports (CLASS) program, created under the Patient Protection and Affordable Care Act, established a federally-administered, voluntary insurance program that allows for working adults to purchase insurance to cover the cost of long term support services. The CLASS program is the first step towards moving away from a welfare-based system, improving consumer choice, and creating a stable funding source for long term care needs. Enrollees in the CLASS program who meet benefit eligibility requirements and need care assistance will receive a cash benefit to pay for supportive services such as home health care, adult day services, assisted living, nursing home care, housing modification, assistive technologies, and transportation assistance. The authors apply David Gil\u27s (1992) model of social policy analysis to assess the effectiveness of this policy alternative to aid in the development of a viable national long term health care solution for the anticipated ongoing health and support service needs of the older adult population

    VALIDATION AND REFINEMENT OF CHEMICAL STABILIZATION PROCEDURES FOR PAVEMENT SUBGRADE SOILS IN OKLAHOMA – VOLUME II (FHWA-OK-11-02(2))

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    For projects involving a chemically stabilized layer as a part of the structural design of the pavement, it is typical to conduct a mix design to assess the additive content needed to achieve a certain unconfined compressive strength (UCS) and to determine the resilient modulus (MR) of the stabilized soil. However, there is considerable uncertainty regarding whether the strength and resilient modulus of the field stabilized soil are consistent with design values determined in the laboratory. A purpose of this study was to compare results of field tests and laboratory tests on chemically stabilized soil at different curing times to assess whether a relationship exists between field and laboratory measurements. The goal was to determine if a field testing method could be used to assess whether the strength and stiffness in the field are consistent with laboratory measurements used for design. In addition, numerous other physical and chemical tests were conducted on the soils with an aim to enhance interpretation of UCS and MR and comparisons to field tests. Field testing included three devices that are portable, quick, and easy to use. These devices include: the Dynamic Cone Penetrometer (DCP), the PANDA penetrometer, and the Portable Falling Weight Deflectometer (PFWD). Laboratory testing was conducted to determine the unconfined compressive strength (UCS) and resilient modulus (MR) of laboratory specimens prepared using additive contents that were similar to samples taken from field test locations. To estimate the additive contents in the field samples, a mineralogical test method known as “whole rock analysis” using x-ray fluorescence (XRF) was investigated. Samples mixed in the laboratory were tested to determine the UCS and MR after curing times of 1, 3, 7, 14, & 28 days. Field tests were conducted at each of the five test sites after curing times that fell within the 1 to 28 day time frame; however, because of construction logistics and weather conditions it was not always possible to match the curing times of laboratory tests or conduct field tests over the full 28 days at every site. Nevertheless, sufficient field data was collected to make meaningful comparisons with laboratory test data. Mineralogical, electrical, chemical, physical and index property testing (Atterberg Limits, linear shrinkage, Total Specific Surface Area (SSA), etc.) was conducted on the natural soils and the stabilized cured samples to observe the relationship of these properties to stabilized soil strength and stiffness. The effect of curing temperature on stabilized strength gain of soils was also examined. The UCS samples were cured at both room temperature (68°F) and at 40°F, which is the minimum ambient temperature specified for chemical stabilization of subgrades. Correlations were examined and involved basic soil measurements (mineralogical, electrical, chemical and index properties) and mechanical properties (UCS and MR), and field test results (DCP, PANDA, and PFWD). Some of the various correlations developed show promise as methods for predicting UCS and MR based on more simply measured soil properties. Relationships between field and laboratory tests also show promise as a means to evaluate strength and stiffness gains in field stabilized soils. Additionally, lower curing temperatures were observed to have an adverse affect on more reactive clayey soils.Final Report, October 2007-December 2010N

    Energy Storage Technology Development for Space Exploration

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    The National Aeronautics and Space Administration is developing battery and fuel cell technology to meet the expected energy storage needs of human exploration systems. Improving battery performance and safety for human missions enhances a number of exploration systems, including un-tethered extravehicular activity suits and transportation systems including landers and rovers. Similarly, improved fuel cell and electrolyzer systems can reduce mass and increase the reliability of electrical power, oxygen, and water generation for crewed vehicles, depots and outposts. To achieve this, NASA is developing non-flow-through proton-exchange-membrane fuel cell stacks, and electrolyzers coupled with low permeability membranes for high pressure operation. The primary advantage of this technology set is the reduction of ancillary parts in the balance-of-plant fewer pumps, separators and related components should result in fewer failure modes and hence a higher probability of achieving very reliable operation, and reduced parasitic power losses enable smaller reactant tanks and therefore systems with lower mass and volume. Key accomplishments over the past year include the fabrication and testing of several robust, small-scale non-flow-through fuel cell stacks that have demonstrated proof-of-concept. NASA is also developing advanced lithium-ion battery cells, targeting cell-level safety and very high specific energy and energy density. Key accomplishments include the development of silicon composite anodes, lithiatedmixed- metal-oxide cathodes, low-flammability electrolytes, and cell-incorporated safety devices that promise to substantially improve battery performance while providing a high level of safety

    Energy Storage Project

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    NASA's Exploration Technology Development Program funded the Energy Storage Project to develop battery and fuel cell technology to meet the expected energy storage needs of the Constellation Program for human exploration. Technology needs were determined by architecture studies and risk assessments conducted by the Constellation Program, focused on a mission for a long-duration lunar outpost. Critical energy storage needs were identified as batteries for EVA suits, surface mobility systems, and a lander ascent stage; fuel cells for the lander and mobility systems; and a regenerative fuel cell for surface power. To address these needs, the Energy Storage Project developed advanced lithium-ion battery technology, targeting cell-level safety and very high specific energy and energy density. Key accomplishments include the development of silicon composite anodes, lithiated-mixed-metal-oxide cathodes, low-flammability electrolytes, and cell-incorporated safety devices that promise to substantially improve battery performance while providing a high level of safety. The project also developed "non-flow-through" proton-exchange-membrane fuel cell stacks. The primary advantage of this technology set is the reduction of ancillary parts in the balance-of-plant--fewer pumps, separators and related components should result in fewer failure modes and hence a higher probability of achieving very reliable operation, and reduced parasitic power losses enable smaller reactant tanks and therefore systems with lower mass and volume. Key accomplishments include the fabrication and testing of several robust, small-scale nonflow-through fuel cell stacks that have demonstrated proof-of-concept. This report summarizes the project s goals, objectives, technical accomplishments, and risk assessments. A bibliography spanning the life of the project is also included

    MicroRNA profiling reveals marker of motor neuron disease in ALS models

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    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents.</jats:p

    X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor

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    The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-ψ[CH(OH)CH_2N]-Pro-Ile-Val-OMe; the K_i is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-Å resolution by using restrained least squares with rms deviations in bond lengths of 0.02 Å and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365
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