65 research outputs found
Improved Lattice Spectroscopy of Minimal Walking Technicolor
We present a numerical study of spectroscopic observables in the SU(2) gauge
theory with two adjoint fermions using improved source and sink operators. We
compare in detail our improved results with previous determinations of masses
that used point sources and sinks and we investigate possible systematic
effects in both cases. Such comparison enables us to clearly assess the impact
of a short temporal extent on the physical picture, and to investigate some
effects due to the finite spatial box. While confirming the IR-conformal
behaviour of the theory, our investigation shows that in order to make firm
quantitative predictions, a better handle on finite size effects is needed.Comment: 33 pages, 30 figures, 18 table
A study of meta-analyses reporting quality in the large and expanding literature of educational technology
As the empirical literature in educational technology continues to grow, meta-analyses are increasingly being used to synthesise research to inform practice. However, not all meta-analyses are equal. To examine their evolution over the past 30 years, this study systematically analysed the quality of 52 meta-analyses (1988–2017) on educational technology. Methodological and reporting quality is defined here as the completeness of the descriptive and methodological reporting features of meta-analyses. The study employed the Meta-Analysis Methodological Reporting Quality Guide (MMRQG), an instrument designed to assess 22 areas of reporting quality in meta-analyses. Overall, MMRQG scores were negatively related to average effect size (i.e., the higher the quality, the lower the effect size). Owing to the presence of poor-quality syntheses, the contribution of educational technologies to learning has been overestimated, potentially misleading researchers and practitioners. Nine MMRQG items discriminated between higher and lower average effect sizes. A publication date analysis revealed that older reviews (1988–2009) scored significantly lower on the MMRQG than more recent reviews (2010–2017). Although the increase in quality bodes well for the educational technology literature, many recent meta-analyses still show only moderate levels of quality. Identifying and using only best evidence-based research is thus imperative to avoid bias. Implications for practice or policy: • Educational technology practitioners should make use of meta-analytical findings that systematically synthesise primary research. • Academics, policymakers and practitioners should consider the methodological quality of meta-analyses as they vary in reliability. • Academics, policymakers and practitioners could avoid misleading bias in research evidence by using the MMRQG to evaluate the quality of meta-analyses. • Meta-analyses with lower MMRQG scores should be considered with caution as they seem to overestimate the effect of educational technology on learning
(31) P and (1) H MRS of DB-1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan.
In vivo (31) P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg intraperitoneally) exhibit a decrease in intracellular pH (pH(i) ) from 6.90 ± 0.05 to 6.33 ± 0.10 (p \u3c 0.001), a slight decrease in extracellular pH (pH(e) ) from 7.00 ± 0.04 to 6.80 ± 0.07 (p \u3e 0.05) and a monotonic decline in bioenergetics (nucleoside triphosphate/inorganic phosphate) of 66.8 ± 5.7% (p \u3c 0.001) relative to the baseline level. Both bioenergetics and pH(i) decreases were sustained for at least 3 h following LND treatment. Liver exhibited a transient intracellular acidification by 0.2 ± 0.1 pH units (p \u3e 0.05) at 20 min post-LND, with no significant change in pH(e) and a small transient decrease in bioenergetics (32.9 ± 10.6%, p \u3e 0.05) at 40 min post-LND. No changes in pH(i) or adenosine triphosphate/inorganic phosphate were detected in the brain (pH(i) , bioenergetics; p \u3e 0.1) or skeletal muscle (pH(i) , pH(e) , bioenergetics; p \u3e 0.1) for at least 120 min post-LND. Steady-state tumor lactate monitored by (1) H MRS with a selective multiquantum pulse sequence with Hadamard localization increased approximately three-fold (p = 0.009). Treatment with LND increased the systemic melanoma response to melphalan (LPAM; 7.5 mg/kg intravenously), producing a growth delay of 19.9 ± 2.0 days (tumor doubling time, 6.15 ± 0.31 days; log(10) cell kill, 0.975 ± 0.110; cell kill, 89.4 ± 2.2%) compared with LND alone of 1.1 ± 0.1 days and LPAM alone of 4.0 ± 0.0 days. The study demonstrates that the effects of LND on tumor pH(i) and bioenergetics may sensitize melanoma to pH-dependent therapeutics, such as chemotherapy with alkylating agents or hyperthermia
Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk
ABSTRACT Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a modified vaccinia Ankara (MVA) prime/intramuscular (i.m.) protein boost regimen induced functional IgG responses in milk, while MVA prime/intranasal (i.n.) boost induced robust milk Env-specific IgA responses. Yet, recent studies have suggested that prevention of postnatal MTCT may require both Env-specific IgA and functional IgG responses in milk. Thus, to investigate whether both responses could be elicited by a combined systemic/mucosal immunization strategy, animals previously immunized with the MVA prime/i.n. boost regimen received an i.n./i.m. combined C.1086 gp120 boost. Remarkably, high-magnitude Env-specific IgA responses were observed in milk, surpassing those in plasma. Furthermore, 29% of vaccine-elicited Env-specific B cells isolated from breast milk were IgA isotype, in stark contrast to the overwhelming predominance of IgG isotype Env-specific B cells in breast milk of chronically HIV-infected women. A clonal relationship was identified between Env-specific blood and breast milk B cells, suggesting trafficking of that cell population between the two compartments. Furthermore, IgA and IgG monoclonal antibodies isolated from Env-specific breast milk B cells demonstrated diverse Env epitope specificities and multiple effector functions, including tier 1 neutralization, antibody-dependent cellular cytotoxicity (ADCC), infected cell binding, and inhibition of viral attachment to epithelial cells. Thus, maternal i.n./i.m. combined immunization is a novel strategy to enhance protective Env-specific IgA in milk, which is subsequently transferred to the infant via breastfeeding. IMPORTANCE Efforts to increase the availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas have proven remarkably successful at reducing HIV vertical transmission rates. However, more than 200,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence, nearly half by postnatal HIV exposure via maternal breast milk. Intriguingly, in the absence of antiretroviral therapy, only 10% of breastfed infants born to HIV-infected mothers acquire the virus, suggesting the existence of naturally protective immune factors in milk. Enhancement of these protective immune factors through maternal vaccination will be a critical strategy to reduce the global pediatric AIDS epidemic. We have previously demonstrated that a high magnitude of HIV Env-specific IgA in milk correlates with reduced risk of infant HIV acquisition. In this study, we describe a novel HIV vaccine regimen that induces potent IgA responses in milk and therefore could potentially protect against breast milk HIV MTCT
Mechanisms of international influence on domestic elite sport policy
In the analysis of sport policy the permeability of domestic policy processes and the significance of non-domestic policy influences is increasingly acknowledged. There is also a growing awareness of the role of domestic institutional arrangements in mediating influences external to the domestic policy system. Taking the interaction between non-domestic influences and domestic policy processes as its starting point the article evaluates, in relation to elite sport, the variety of mechanisms that have been identified as linking the domestic and non-domestic policy spheres. It is argued that the mechanisms vary in relation to the locus of initiative, the basis of engagement, the key relationships and the nature of power relationships. It is also argued that in many countries in relation to elite sport policy there is a dual process in operation of domestically initiated policy learning and non-domestically initiated policy harmonisation through policy regimes
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
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