248 research outputs found

    Anger Displayed by Second Grade Students Who have Experienced Periodic, Planned Role-Playing/Discussion Activities and a Comparable Group of Second Grade Students Who have Not Experienced Periodic, Planned Role-Playing/Discussion Activities

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    Is there a difference between how a group of second grade students who have experienced periodic, planned role playing/ discussion activities and a comparable group of second grade students who have not experienced periodic, planned role playing/ discussion activities will display anger when presented with problem situations

    When innovation outpaces regulations:The legal challenges for direct-to-patient supply of investigational medicinal products

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    AIMS: We profile the lack of specific regulation for direct‐to‐patient postal supply (DTP) of clinical trial medications (investigational medicinal products, IMPs) calling for increased efficiency of patient‐centred multi‐country remote clinical trials. METHODS: Questionnaires emailed to 28 European Economic Area (EEA) Medical Product Licensing Authorities (MPLAs) and Swissmedic MPLA were analysed in 2019/2020. The questionnaire asked whether DTP of IMPs was legal, followed by comparative legal analysis profiling relevant national civil and criminal liability provisions in 30 European jurisdictions (including The Netherlands), finally summarising accessible COVID‐19‐related guidance in searches of 30 official MPLA websites in January 2021. RESULTS: Twenty MPLAs responded. Twelve consented to response publication in 2021. DTP was not widely authorised, though different phrases were used to explain this. Our legal review of national laws in 29 EEA jurisdictions and Switzerland did not identify any specific sanctions for DTP of IMPs; however, we identified potential national civil and criminal liability provisions. Switzerland provides legal clarity where DTP of IMPs is conditionally legal. MPLA webpage searches for COVID‐19 guidance noted conditional acceptance by 19 MPLAs. CONCLUSIONS: Specific national legislation authorising DTP of IMPs, defining IMP categories, and conditions permitting the postage and delivery by courier in an EEA‐wide clinical trial, would support innovative patient‐centred research for multi‐country remote clinical trials. Despite it appearing more acceptable to do this between EU Member States, provided each EU MPLA and ethics board authorises it, temporary Covid‐19 restrictions in national Good Clinical Practice (GCP) guidance discourages innovative research into the safety and effectiveness of clinical trial medications

    The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodeling

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    The adenosine diphosphate (ADP) receptor P2RY12 (purinergic receptor P2Y, G protein coupled, 12) plays a critical role in platelet aggregation, and P2RY12 inhibitors are used clinically to prevent cardiac and cerebral thrombotic events. Extracellular ADP has also been shown to increase osteoclast (OC) activity, but the role of P2RY12 in OC biology is unknown. Here, we examined the role of mouse P2RY12 in OC function. Mice lacking P2ry12 had decreased OC activity and were partially protected from age-associated bone loss. P2ry12(–/–) OCs exhibited intact differentiation markers, but diminished resorptive function. Extracellular ADP enhanced OC adhesion and resorptive activity of WT, but not P2ry12(–/–), OCs. In platelets, ADP stimulation of P2RY12 resulted in GTPase Ras-related protein (RAP1) activation and subsequent α(IIb)β(3) integrin activation. Likewise, we found that ADP stimulation induced RAP1 activation in WT and integrin β(3) gene knockout (Itgb3(–/–)) OCs, but its effects were substantially blunted in P2ry12(–/–) OCs. In vivo, P2ry12(–/–) mice were partially protected from pathologic bone loss associated with serum transfer arthritis, tumor growth in bone, and ovariectomy-induced osteoporosis: all conditions associated with increased extracellular ADP. Finally, mice treated with the clinical inhibitor of P2RY12, clopidogrel, were protected from pathologic osteolysis. These results demonstrate that P2RY12 is the primary ADP receptor in OCs and suggest that P2RY12 inhibition is a potential therapeutic target for pathologic bone loss

    Smoke, curtains and mirrors: the production of race through time and title registration

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    This article analyses the temporal effects of title registration and their relationship to race. It traces the move away from the retrospection of pre-registry common law conveyancing and toward the dynamic, future-oriented Torrens title registration system. The Torrens system, developed in early colonial Australia, enabled the production of ‘clean’, fresh titles that were independent of their predecessors. Through a process praised by legal commentators for ‘curing’ titles of their pasts, this system produces indefeasible titles behind its distinctive ‘curtain’ and ‘mirror’, which function similarly to magicians’ smoke and mirrors by blocking particular realities from view. In the case of title registries, those realities are particular histories of and relationships with land, which will not be protected by property law and are thus made precarious. Building on interdisciplinary work which theorises time as a social tool, I argue that Torrens title registration produces a temporal order which enables land market coordination by rendering some relationships with land temporary and making others indefeasible. This ordering of relationships with land in turn has consequences for the human subjects who have those relationships, cutting futures short for some and guaranteeing permanence to others. Engaging with Renisa Mawani and other critical race theorists, I argue that the categories produced by Torrens title registration systems materialise as race

    A Q-methodology study of flare help-seeking behaviours and different experiences of daily life in rheumatoid arthritis

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    © 2014 Lin et al.; licensee BioMed Central Ltd. Background: Previous studies have not addressed rheumatoid arthritis (RA) patients' help-seeking behaviours for RA flares, and only one small qualitative study has addressed how patients experience daily life on current treatment regimes. Thus, this study aims to identify clusters of opinion related to RA patients' experiences of daily life on current treatments, and their help-seeking behaviours for RA flares. Methods: Using Q-methodology (a methodology using qualitative and quantitative methods to sort people according to subjective experience), two separate studies were conducted with the same sample of RA patients (mean age 55, 73% female). Thirty participants sorted 39 statements about daily life (Q-study 1) and 29 participants separately sorted 23 statements about flare help-seeking (Q-study 2). Data were examined using Q-factor analysis. Results: Daily life with RA (Q-study 1): Three factors relating to the experience of living with RA were extracted and explained. Patients belonging to Factor A (mean age 62, 86% female) use effective self-management techniques to control the daily impact of RA. Those in Factor B (mean age 55, 75% male) struggle to self-manage and cope. Whilst patients in Factor C (mean age 42, 100% female) prioritise life responsibilities over their RA, reporting less impact. Flare help-seeking (Q-study 2): Two factors explaining the experience of flare help-seeking (unrelated to the factors from Q-study 1) were extracted and explained. Factor X (68.8% on biologics) reported seeking help quickly, believing the medical team is there to help. Factor Y (0% on biologics) delay help-seeking, concerned about wasting the rheumatologist's time, believing they should manage alone. All participants agreed they sought help due to intense pain and persistent, unmanageable symptoms. Conclusions: Patients with different characteristics appear to manage RA life in different ways and men may struggle more than women. Whilst all patients are prompted to seek help by persistent, unmanageable symptoms, some delay help-seeking. Further research is needed to quantify the severity of daily symptoms, the level of symptoms needed for patients to define themselves as in flare and to understand the support needs of RA men

    Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice

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    The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood.Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O(2) for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O(2) than in saline/RA mice. Isolated cardiomyocytes from LPS/O(2) mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O(2) mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O(2) mice.These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health

    THE K2-ESPRINT PROJECT. V. A SHORT-PERIOD GIANT PLANET ORBITING A SUBGIANT STAR

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    We report on the discovery and characterization of the transiting planet K2-39b (EPIC 206247743b). With an orbital period of 4.6 days, it is the shortest-period planet orbiting a subgiant star known to date. Such planets are rare, with only a handful of known cases. The reason for this is poorly understood but may reflect differences in planet occurrence around the relatively high-mass stars that have been surveyed, or may be the result of tidal destruction of such planets. K2-39 (EPIC 206247743) is an evolved star with a spectroscopically derived stellar radius and mass of 3.88 [subscript -0.42] [superscript +0.48] R [subscript ⊙] and 1.53[subscript-0.12] [superscript +0.13] M[subscript ⊙], respectively, and a very close-in transiting planet, with a/R [subscript asterisk]= 3.4 Radial velocity (RV) follow-up using the HARPS, FIES, and PFS instruments leads to a planetary mass of 50.3 [subscript -9.4] [superscript +9.7] M [subscript ⊙]. In combination with a radius measurement of 8.3 ± 1.1 R [subscript oplus], this results in a mean planetary density of 0.50 [subscript -0.17] [superscript +0.29] g cm [superscript -3]. We furthermore discover a long-term RV trend, which may be caused by a long-period planet or stellar companion. Because K2-39b has a short orbital period, its existence makes it seem unlikely that tidal destruction is wholly responsible for the differences in planet populations around subgiant and main-sequence stars. Future monitoring of the transits of this system may enable the detection of period decay and constrain the tidal dissipation rates of subgiant stars

    Firm insoles effectively reduce hemolysis in runners during long distance running - a comparative study

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    <p>Abstract</p> <p>Background</p> <p>Shock absorbing insoles are effective in reducing the magnitude and rate of loading of peak impact forces generated at foot strike during running, whereas the foot impact force during running has been considered to be an important cause of intravascular hemolysis in long distance runners. Objective of this study was to evaluate the intravascular hemolysis during running and compare the effect of two different types of insoles (Soft and Firm) on hemolysis.</p> <p>Methods</p> <p>Twenty male long and middle distance runners volunteered to participate in this study. We selected two insoles (Soft and Firm) according to their hardness level (SHORE 'A' scale). Participants were randomly assigned to the soft insole (group 1) and firm insole (group 2) group with ten athletes in each group. Each athlete completed one hour of running at the calculated target heart rate (60-70%). Venous blood samples were collected before and immediately after running. We measured unconjucated bilirubin (mg/dl), lactate dehydrogenase (μ/ml), hemoglobin (g/l) and serum ferritin (ng/ml) as indicators of hemolysis.</p> <p>Results</p> <p>Our study revealed a significant increase in the mean values of unconjucated bilirubin (P < 0.05) while running with soft insoles indicating the occurrence of hemolysis in this group of athletes. Graphical analysis revealed an inverse relationship between hardness of insoles and hemolysis for the observed values.</p> <p>Conclusion</p> <p>Our results indicate that intravascular hemolysis occurs in athletes during long distance running and we conclude that addition of firm insoles effectively reduces the amount of hemolysis in runners compared to soft insoles.</p
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