305 research outputs found

    PMS41 THE IMPACT OF MEDICATION ADHERENCE ON THE COST OF OSTEOPOROSIS FRACTURES IN GERMANY: A MODELLING APPROACH

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    Enhancing home health mobile phone app usability through general smartphone training: usability and learnability case study.

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    peer-reviewedEach year, millions of older adults fall, with more than 1 out of 4 older people experiencing a fall annually, thereby causing a major social and economic impact. Falling once doubles oneâ s chances of falling again, making fall prediction an important aspect of preventative strategies. In this study, 22 older adults aged between 65 and 85 years were trained in the use of a smartphone-based fall prediction system. The system is designed to continuously assess fall risk by measuring various gait and balance parameters using a smart insole and smartphone, and is also designed to detect falls. The use case of the fall prediction system in question required the users to interact with the smartphone via an app for device syncing, data uploads, and checking system status. The objective of this study was to observe the effect that basic smartphone training could have on the user experience of a group that is not technically proficient with smartphones when using a new connected health system. It was expected that even short rudimentary training could have a large effect on user experience and therefore increase the chances of the group accepting the new technology. All participants received training on how to use the system smartphone app; half of the participants (training group) also received extra training on how to use basic functions of the smartphone, such as making calls and sending text messages, whereas the other half did not receive this extra training (no extra training group). Comparison of training group and no extra training group was carried out using metrics such as satisfaction rating, time taken to complete tasks, cues required to complete tasks, and errors made during tasks. The training group fared better in the first 3 days of using the system. There were significant recorded differences in number of cues required and errors committed between the two groups. By the fourth and fifth day of use, both groups were performing at the same level when using the system. Supplementary basic smartphone training may be critical in trials where a smartphone appâ based system for health intervention purposes is being introduced to a population that is not proficient with technology. This training could prevent early technology rejection and increase the engagement of older participants and their overall user experience with the system.PUBLISHEDpeer-reviewe

    An empirical investigation of the influence of collaboration in Finance on article impact

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    We investigate the impact of collaborative research in academic Finance literature to find out whether and to what extent collaboration leads to higher impact articles (6,667 articles across 2001-2007 extracted from the Web of Science). Using the top 5 % as ranked by the 4-year citation counts following publication, we also follow related secondary research questions such as the relationships between article impact and author impact; collaboration and average author impact of an article; and, the nature of geographic collaboration. Key findings indicate: collaboration does lead to articles of higher impact but there is no significant marginal value for collaboration beyond three authors; high impact articles are not monopolized by high impact authors; collaboration and the average author impact of high-impact articles are positively associated, where collaborative articles have a higher mean author impact in comparison to single-author articles; and collaboration among the authors of high impact articles is mostly cross-institutional

    MDA-5 Recognition of a Murine Norovirus

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    Noroviruses are important human pathogens responsible for most cases of viral epidemic gastroenteritis worldwide. Murine norovirus-1 (MNV-1) is one of several murine noroviruses isolated from research mouse facilities and has been used as a model of human norovirus infection. MNV-1 infection has been shown to require components of innate and adaptive immunity for clearance; however, the initial host protein that recognizes MNV-1 infection is unknown. Because noroviruses are RNA viruses, we investigated whether MDA5 and TLR3, cellular sensors that recognize dsRNA, are important for the host response to MNV-1. We demonstrate that MDA5−/− dendritic cells(DC) have a defect in cytokine response to MNV-1. In addition, MNV-1 replicates to higher levels in MDA5−/− DCs as well as in MDA5−/− mice in vivo. Interestingly, TLR3−/− DCs do not have a defect in vitro, but TLR3−/− mice have a slight increase in viral titers. This is the first demonstration of an innate immune sensor for norovirus and shows that MDA5 is required for the control of MNV-1 infection. Knowledge of the host response to MNV-1 may provide keys for prevention and treatment of the human disease

    Multiple P2Y receptors couple to calcium-dependent, chloride channels in smooth muscle cells of the rat pulmonary artery

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    BACKGROUND: Uridine 5'-triphosphate (UTP) and uridine 5'-diphosphate (UDP) act via P2Y receptors to evoke contraction of rat pulmonary arteries, whilst adenosine 5'-triphosphate (ATP) acts via P2X and P2Y receptors. Pharmacological characterisation of these receptors in intact arteries is complicated by release and extracellular metabolism of nucleotides, so the aim of this study was to characterise the P2Y receptors under conditions that minimise these problems. METHODS: The perforated-patch clamp technique was used to record the Ca(2+)-dependent, Cl(- )current (I(Cl,Ca)) activated by P2Y receptor agonists in acutely dissociated smooth muscle cells of rat small (SPA) and large (LPA) intrapulmonary arteries, held at -50 mV. Contractions to ATP were measured in isolated muscle rings. Data were compared by Student's t test or one way ANOVA. RESULTS: ATP, UTP and UDP (10(-4)M) evoked oscillating, inward currents (peak = 13–727 pA) in 71–93% of cells. The first current was usually the largest and in the SPA the response to ATP was significantly greater than those to UTP or UDP (P < 0.05). Subsequent currents tended to decrease in amplitude, with a variable time-course, to a level that was significantly smaller for ATP (P < 0.05), UTP (P < 0.001) and UDP (P < 0.05) in the SPA. The frequency of oscillations was similar for each agonist (mean≈6–11.min(-1)) and changed little during agonist application. The non-selective P2 receptor antagonist suramin (10(-4)M) abolished currents evoked by ATP in SPA (n = 4) and LPA (n = 4), but pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (10(-4)M), also a non-selective P2 antagonist, had no effect (n = 4, 5 respectively). Currents elicited by UTP (n = 37) or UDP (n = 14) were unaffected by either antagonist. Contractions of SPA evoked by ATP were partially inhibited by PPADS (n = 4) and abolished by suramin (n = 5). Both antagonists abolished the contractions in LPA. CONCLUSION: At least two P2Y subtypes couple to I(Cl,Ca )in smooth muscle cells of rat SPA and LPA, with no apparent regional variation in their distribution. The suramin-sensitive, PPADS-resistant site activated by ATP most resembles the P2Y(11 )receptor. However, the suramin- and PPADS-insensitive receptor activated by UTP and UDP does not correspond to any of the known P2Y subtypes. These receptors likely play a significant role in nucleotide-induced vasoconstriction

    Rabies Virus Infection Induces Type I Interferon Production in an IPS-1 Dependent Manner While Dendritic Cell Activation Relies on IFNAR Signaling

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    As with many viruses, rabies virus (RABV) infection induces type I interferon (IFN) production within the infected host cells. However, RABV has evolved mechanisms by which to inhibit IFN production in order to sustain infection. Here we show that RABV infection of dendritic cells (DC) induces potent type I IFN production and DC activation. Although DCs are infected by RABV, the viral replication is highly suppressed in DCs, rendering the infection non-productive. We exploited this finding in bone marrow derived DCs (BMDC) in order to differentiate which pattern recognition receptor(s) (PRR) is responsible for inducing type I IFN following infection with RABV. Our results indicate that BMDC activation and type I IFN production following a RABV infection is independent of TLR signaling. However, IPS-1 is essential for both BMDC activation and IFN production. Interestingly, we see that the BMDC activation is primarily due to signaling through the IFNAR and only marginally induced by the initial infection. To further identify the receptor recognizing RABV infection, we next analyzed BMDC from Mda-5−/− and RIG-I−/− mice. In the absence of either receptor, there is a significant decrease in BMDC activation at 12h post infection. However, only RIG-I−/− cells exhibit a delay in type I IFN production. In order to determine the role that IPS-1 plays in vivo, we infected mice with pathogenic RABV. We see that IPS-1−/− mice are more susceptible to infection than IPS-1+/+ mice and have a significantly increased incident of limb paralysis

    Zebrafish Mutants calamity and catastrophe Define Critical Pathways of Gene–Nutrient Interactions in Developmental Copper Metabolism

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    Nutrient availability is an important environmental variable during development that has significant effects on the metabolism, health, and viability of an organism. To understand these interactions for the nutrient copper, we used a chemical genetic screen for zebrafish mutants sensitive to developmental copper deficiency. In this screen, we isolated two mutants that define subtleties of copper metabolism. The first contains a viable hypomorphic allele of atp7a and results in a loss of pigmentation when exposed to mild nutritional copper deficiency. This mutant displays incompletely penetrant skeletal defects affected by developmental copper availability. The second carries an inactivating mutation in the vacuolar ATPase that causes punctate melanocytes and embryonic lethality. This mutant, catastrophe, is sensitive to copper deprivation revealing overlap between ion metabolic pathways. Together, the two mutants illustrate the utility of chemical genetic screens in zebrafish to elucidate the interaction of nutrient availability and genetic polymorphisms in cellular metabolism
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