1,792 research outputs found

    "Re-educating" tumor-associated macrophages by targeting NF-kappaB

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    The nuclear factor kappaB (NF-kappaB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-kappaB in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive "alternative" phenotype that requires IkappaB kinase beta-mediated NF-kappaB activation. When NF-kappaB signaling is inhibited specifically in TAMs, they become cytotoxic to tumor cells and switch to a "classically" activated phenotype; IL-12(high), major histocompatibility complex II(high), but IL-10(low) and arginase-1(low). Targeting NF-kappaB signaling in TAMs also promotes regression of advanced tumors in vivo by induction of macrophage tumoricidal activity and activation of antitumor activity through IL-12-dependent NK cell recruitment. We provide a rationale for manipulating the phenotype of the abundant macrophage population already located within the tumor microenvironment; the potential to "re-educate" the tumor-promoting macrophage population may prove an effective and novel therapeutic approach for cancer that complements existing therapies

    'It shouldn't be this hard': exploring the challenges of rural health research

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    Health research is important for innovation and assessment of health status and health interventions, and maintaining a strong, engaged cohort of rural health researchers is essential for the ongoing improvement of the health of rural populations. Ethical guidelines and processes ensure research is undertaken in a way that protects and, where possible, empowers participants. We set out to systematically examine and document the challenges posed by ethics and governance processes for rural health researchers in Western Australia (WA) and the impact on the research undertaken. In this qualitative study, fifteen WA-based rural health researchers were interviewed. The identified challenges included inefficient systems, gatekeeping, apparent resistance to research and the lack of research experience of those involved in approval processes. For researchers seeking to conduct studies to improve rural and Aboriginal health, extended delays in approvals can hold up and impede research, ultimately changing the nature of the research undertaken and constraining the willingness of practitioners and researchers to undertake health research. Unwieldy ethics processes were seen to have a particularly onerous impact on rural research pertaining to service delivery, multiple sites, and research involving Aboriginal people, impeding innovation and inquiry in areas where it is much needed.Heath Greville, Emma Haynes, Robin Kagie and Sandra C Thompso

    Prevalence and Determinants of Hearing Loss Among Primary School Children in Selected Schools in the Central Region of Ghana

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    Hearing loss in children often inhibits speech and language development, thus affecting academic performance, social and emotional well-being. Thus a comparative cross-sectional study was conducted in three primary schools in Ghana to assess hearing of the children attending those schools and also compare differences between these schools based on the pupils’ socioeconomic backgrounds. The data was used to determine prevalence of hearing loss in the schools. A comparison was then made between the results obtained among children attending the more affluent school and the less affluent schools. A total of 773 pupils were included in this study even though 839 pupils were screened as some pupils failed to adequately complete the questionnaires. The average age was 10 years with a standard deviation of 2.65. Significant hearing loss was identified in 4 children (0.5%). Abnormal tympanometry was identified in 86 (10.2%). Abnormal otologic findings identified included cerumen impaction in 73 children (36.5%), acute otitis externa in 7, acute otitis media in 6 and foreign bodies in 10. Schools with lower socioeconomic pupils had a higher prevalence of abnormal tympanometry but there was no difference in hearing loss prevalence. In conclusion, unidentified hearing loss in the three basic schools in Ghana was uncommon and prevalence was not impacted by the school’s socioeconomic background. However, a significant portion had abnormal middle ear function or external auditory canal occlusion from cerumen impaction and thus required further management

    Challenges in managing acute cardiovascular diseases and follow up care in rural areas: a narrative review

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    This narrative review explores relevant literature that is related to the challenges in implementing evidence-based management for clinicians in rural and remote areas, while primarily focussing on management of acute coronary syndrome (ACS) and follow up care. A targeted literature search around rural/urban differences in the management of ACS, cardiovascular disease, and cardiac rehabilitation identified multiple issues that are related to access, including the ability to pay, transport and geographic distances, delays in patients seeking care, access to diagnostic testing, and timely treatment in an appropriate facility. Workforce shortages or lack of ready access to relevant expertise, cultural differences, and complexity that arises from comorbidities and from geographical isolation amplified diagnostic challenges. Given the urgency in management of ACS, rural clinicians must act quickly to achieve optimal patient outcomes. New technologies and quality improvement approaches enable better access to rapid diagnosis, as well as specialist input and care. Achieving an uptake of cardiac rehabilitation in rural and remote settings poses challenges that may reduce with the use of alternative models to centre-based rehabilitation and use of modern technologies. Expediting improvement in cardiovascular outcomes and reducing rural disparities requires system changes and that clinicians embrace attention to prevention, emergency management, and follow up care in rural contexts.Sandra C. Thompson, Lee Nedko, Judith Katzenellenbogen, Mohammad Akhtar Hussain and Frank Sanfilipp

    Monte Carlo integration in Glauber model analysis of reactions of halo nuclei

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    Reaction and elastic differential cross sections are calculated for light nuclei in the framework of the Glauber theory. The optical phase-shift function is evaluated by Monte Carlo integration. This enables us to use the most accurate wave functions and calculate the phase-shift functions without approximation. Examples of proton nucleus (e.g. p-6^6He, p-6^6Li) and nucleus-nucleus (e.g. 6^6He12-^{12}C) scatterings illustrate the effectiveness of the method. This approach gives us a possibility of a more stringent analysis of the high-energy reactions of halo nuclei.Comment: 20 pages, 8 figure

    Resonant Absorption as Mode Conversion?

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    Resonant absorption and mode conversion are both extensively studied mechanisms for wave "absorption" in solar magnetohydrodynamics (MHD). But are they really distinct? We re-examine a well-known simple resonant absorption model in a cold MHD plasma that places the resonance inside an evanescent region. The normal mode solutions display the standard singular resonant features. However, these same normal modes may be used to construct a ray bundle which very clearly undergoes mode conversion to an Alfv\'en wave with no singularities. We therefore conclude that resonant absorption and mode conversion are in fact the same thing, at least for this model problem. The prime distinguishing characteristic that determines which of the two descriptions is most natural in a given circumstance is whether the converted wave can provide a net escape of energy from the conversion/absorption region of physical space. If it cannot, it is forced to run away in wavenumber space instead, thereby generating the arbitrarily small scales in situ that we recognize as fundamental to resonant absorption and phase mixing. On the other hand, if the converted wave takes net energy way, singularities do not develop, though phase mixing may still develop with distance as the wave recedes.Comment: 23 pages, 8 figures, 2 tables; accepted by Solar Phys (July 9 2010

    Effective Electromagnetic Lagrangian at Finite Temperature and Density in the Electroweak Model

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    Using the exact propagators in a constant magnetic field, the effective electromagnetic Lagrangian at finite temperature and density is calculated to all orders in the field strength B within the framework of the complete electroweak model, in the weak coupling limit. The partition function and free energy are obtained explicitly and the finite temperature effective coupling is derived in closed form. Some implications of this result, potentially interesting to astrophysics and cosmology, are discussed.Comment: 14 pages, Revtex

    Environmental effect on egress simulation

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    Abstract. Evacuation and egress simulations can be a useful tool for studying the effect of design decisions on the flow of agent movement. This type of simulation can be used to determine before hand the effect of design decisions and enable exploration of potential improvements. In this work, we study at how agent egress is affected by the environment in real world and large scale virtual environments and investigate metrics to analyze the flow. Our work differs from many evacuation systems in that we support grouping restrictions between agents (e.g., families or other social groups traveling together), and model scenarios with multiple modes of transportation with physically realistic dynamics (e.g., individuals walk from a building to their own cars and leave only when all people in the group arrive).
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