Oxidation of NiAl–9Mo eutectics with three different second-phase Mo dispersion sizes was investigated at 900°C in dry and wet air. Good oxidation resistance via alumina formation was observed in dry ...air, with MoO3 volatilization minimized by submicron Mo dispersions. However, although mass change measurements were similar in dry/wet air, extensive volatilization and in-place internal oxidation of prior Mo phase regions was observed in wet air. The ramifications of this phenomenon for the development of multiphase high-temperature alloys are discussed.
A pan-Arctic sea-ice-ocean prediction system is assessed in terms of its ability to predict sea-ice velocity. This system is based on the Regional Ice Ocean Prediction System running operationally at ...the Canadian Centre for Meteorological and Environmental Prediction. A form drag parameterization is implemented in the system to allow spatially and temporally varying neutral drag coefficients depending on the sea-ice morphological characteristics. Simulated ice velocity is assessed using data from the International Arctic Buoy Programme, as well as ice motion derived from Environment and Climate Change Canada's synthetic aperture radar automated ice-tracking system. Results indicate that introducing the form drag parameterization systematically increases the sea-ice velocity and exacerbates a positive bias in summer already present in the previous version in which constant neutral drag coefficients were used. The ice strength parameterization used in the model rheology is found to affect the simulated ice drift significantly. Introducing modifications to the ice strength formulation and the empirical parameters helped alleviate the ice velocity bias.
Cardiac and respiratory motion derived image artefacts are reduced when data are acquired with cardiac and respiratory synchronisation. Where steady state imaging techniques are required in small ...animals, synchronisation is most commonly performed using retrospective gating techniques but these invoke an inherent time penalty. This paper reports the development of prospective gating techniques for cardiac and respiratory motion desensitised MRI with significantly reduced minimum scan time compared to retrospective gating.
Prospective gating incorporating the automatic reacquisition of data corrupted by motion at the entry to each breath was implemented in short TR 3D spoiled gradient echo imaging. Motion sensitivity was examined over the whole mouse body for scans performed without gating, with respiratory gating, and with cardio-respiratory gating. The gating methods were performed with and without automatic reacquisition of motion corrupted data immediately after completion of the same breath. Prospective cardio-respiratory gating, with acquisition of 64 k-space lines per cardiac R-wave, was used to enable whole body DCE-MRI in the mouse.
Prospective cardio-respiratory gating enabled high fidelity steady state imaging of physiologically mobile organs such as the heart and lung. The automatic reacquisition of data corrupted by motion at the entry to each breath minimised respiratory motion artefact and enabled a highly efficient data capture that was adaptive to changes in the inter-breath interval. Prospective cardio-respiratory gating control enabled DCE-MRI to be performed over the whole mouse body with the acquisition of successive image volumes every 12–15 s at 422 μm isotropic resolution.
Highly efficient cardio-respiratory motion desensitised steady state MRI can be performed in small animals with prospective synchronisation, centre-out phase-encode ordering, and the automatic reacquisition of data corrupted by motion at the entry to each breath. The method presented is robust against spontaneous changes in the breathing rate. Steady state imaging with prospective cardio-respiratory gating is much more efficient than with retrospective gating, and enables the examination of rapidly changing systems such as those found when using DCE-MRI.
Falls are a significant source of preventable morbidity and mortality in the United States, particularly amongst older individuals. This DPI project sought to answer the clinical question; Is the ...John Hopkins Fall Risk Assessment Tool more sensitive and specific in identifying adult medical patients at risk for falls than the New York Presbyterian Fall Risk Assessment Tool as measured by differences in the number of falls over a two-week project period. This DPI project used Greenhalgh’s dissemination of innovations model for implementing change within large organizations to engage staff in the process of designing, reviewing, and evaluating a clinical practice improvement project. This DPI project used a quantitative, quasi-experimental project design to evaluate the effects of two fall risk assessment tools on the number of falls in a convenience sample of 115 adult medical patients (ages 23-97, mean 64.6) over two weeks at a large tertiary care medical center in the Northeastern United States. The project results were analyzed using crosstab and chi-square analysis, which indicated that the John Hopkins tool may be more sensitive (100%) and specific (71.2%) (p=0.275) in this population. These findings showed an improved identification of at-risk patients but also illuminated areas that need to be explored in future projects. Although the results are not statistically significant, the John Hopkins Fall Risk Assessment Tool may be a useful tool for evaluating fall risk. Additional project sites should be considered to provide a more substantial basis for changing current fall risk assessment practices.
•A model of nutritional management and beef sustainability was created and validated.•Diet changes substantially reduced land use, water use and GHG emissions.•Consumers WTP for environmental ...production practices helped improve sustainability.•Intensive pasture management was an economical method to improve sustainability.•Rainfall patterns markedly altered strategies required to reduce resource use.
System sustainability balances environmental impact, economic viability and social acceptability. Assessment methods to investigate impacts of enterprise management and consumer decisions on sustainability of beef cattle operations are critically needed. Tools of this nature are especially important given the predictions of climate variability and the dependence of beef production systems on forage availability. A model optimizing nutritional and pasture management was created to examine the environmental impact of beef production. The model integrated modules calculating cradle-to-farm gate environmental impact, diet cost, pasture growth and willingness to pay (WTP). Least-cost diet and pasture management options served as a baseline to which environmental-impact reducing scenarios were compared. Economic viability was ensured by a constraint limiting change in diet cost to less than consumer WTP. Increased WTP was associated with improved social acceptability. Model outputs were evaluated by comparing to published data. Sensitivity analysis of the WTP constraint was conducted. A series of scenarios then examined how forecasted changes in precipitation patterns might alter forage supply and opportunities to reduce environmental impact in three regions in the United States. On a national scale, single-objective optimization indicated individual reductions in greenhouse gases (GHG), land use and water use of 3.6%, 5.4% and 4.3% were possible by changing diets. Multi-objective optimization demonstrated that GHG, land and water use could be simultaneously reduced by 2.3%. To achieve this change, cow–calf diets relied on grass hay, continuously- or rotationally-grazed irrigated and fertilized pasture as well as rotationally-grazed pasture. Stocker diets used rotationally-grazed, irrigated and fertilized pasture and feedlot diets used grass hay as a forage source. The model was sensitive to consumer WTP. When alternative precipitation patterns were simulated, opportunities to decrease the environmental impact of beef production in the Pacific Northwest and Texas were reduced by precipitation changes; whereas opportunities in the Midwest improved. Economic viability, rather than biological limitations, reduced the potential to improve environmental impact under future precipitation scenarios. Decreased spring rainfall resulted in lower pasture yields and required greater use of stored forages. Related increases in diet cost reduced opportunities to appropriate funds toward investment in environmental-impact reducing pasture management strategies. The model developed in this study is a robust tool that can be used to assess the impacts of enterprise management and consumer decisions on beef production sustainability.
After the introduction of the hepatitis B vaccine in the United States in 1982, a greater than 90% reduction in new infections was achieved. However, approximately 1000 new cases of perinatal ...hepatitis B infection are still identified annually in the United States. Prevention of perinatal hepatitis B relies on the proper and timely identification of infants born to mothers who are hepatitis B surface antigen positive and to mothers with unknown status to ensure administration of appropriate postexposure immunoprophylaxis with hepatitis B vaccine and immune globulin. To reduce the incidence of perinatal hepatitis B transmission further, the American Academy of Pediatrics endorses the recommendation of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention that all newborn infants with a birth weight of greater than or equal to 2000 g receive hepatitis B vaccine by 24 hours of age.
The definition of 'uncertainty' proposed by Bruno de Finetti and Leonard J. Savage is significantly different from the one advanced by J. M. Keynes and Frank H. Knight. Recent studies seem to have ...overlooked this aspect of de Finetti and Savage's 1962 paper Sul Modo di Scegliere le Probabilita Iniziali. This particular work has been cited as supporting the claim that there are similarities between the de Finetti-Savage's conception of uncertainty and the Keynes-Knight's approach. This claim, however, loses much of its appeal once it is realized that the discussion by de Finetti and Savage involves only the initial probabilities.
Abstract 2707
The biology of follicular lymphoma (FL) is largely dictated by the immune-effector and stromal cells that comprise its tumor microenvironment. Recent studies have demonstrated that ...various infiltrating T-cell populations can be predictive of clinical outcome, with two such populations, follicular helper T-cells (TFH) and regulatory T-cells (Treg) likely playing critical roles in the biology of this disease. TFH are normally responsible for the activation and maintenance of germinal center B-cells while Tregs suppress effector T-cell priming and function as well as suppress normal B-cell proliferation and differentiation. There is also data to support the notion that both of these cells have direct and/or indirect effects on FL B-cells. These cells and other immune-effector cells within the FL microenvironment have dynamic interactions with mesenchymal stromal cells (MSC), multipotent cells residing in most adult tissues, which can be recruited by FL B-cells into the tumor microenvironment where they inhibit anti-lymphoma T-cell responses and FL B-cell apoptosis. We hypothesized that such MSC play a role in modulating TFH viability, similar to what has been previously reported for Treg, and herein we show such a novel role for MSC, that being the selective support of FL-derived TFH populations.
To determine the effect of MSC on the viability of discrete T-cell populations infiltrating FL lymph nodes (FLN), un-separated single cell suspensions (SCS) from FLN (n=13) were cultured for 48 hours alone or with normal tonsillar-derived MSC. The fold change in the proportion of CD4 T-cells that are TFH (CXCR5+PD-1+Bcl-6+), Tregs (CD25+FoxP3+), TH1 (T-bet+), TH2 (GATA-3+) or TH17 (ROR-gamma-t+) cells in SCS incubated with MSC was compared to that of SCS incubated without MSC. A 2.3-fold increase in the percentage of TFH (p=0.006) cells and a 2-fold increase in the percentage of Tregs (p=0.007) were observed in the SCS cultured with MSC compared to those cultured without MSC. The effect of MSC in maintaining TFH and Tregs was selective, as in contrast, the proportion of T-cells expressing the canonical TH1, TH2 and TH17 transcription factors was not increased after culture with MSC. B-cells provide survival signals to TFH and stromal cells provide survival signals to B-cells, therefore we next determined whether the stromal support of TFH was mediated via B-cells. Both purified FL T-cells and B-cell-depleted FL SCS cultured on MSC showed a similar increase in TFH (and Treg) populations as seen with un-separated FL-B SCS, indicating that MSC support of TFH and Tregs was independent of B-cells. MSC only partially supported TFH and Treg populations in transwell experiments suggesting a role for both cell-cell contact and soluble factors. In this regard, IL-6 and IL-21 are known to be secreted by MSC and to signal through gp130 receptors on TFH to induce the transcription of Bcl-6, which is required for TFH differentiation. Blocking IL-6 and IL-21 decreased MSC support of TFH by 42% (p=0.021), while reducing MSC support of Tregs by only 17% (p=0.018) suggesting that IL-6 and IL-21 mediate, in part, the protective effect that MSC have on TFH but that other cytokines are likely to play a role in supporting Tregs. Finally, we have shown that FLN-derived MSC support both FL T-cells and normal lymph node T-cells to a similar extent as the tonsillar MSC used in these experiments. This provides support for the use of tonsillar MSC in these experiments as we were able to generate and expand these more consistently than MSC from FLN, which allowed us to use a consistent MSC product for all experiments.
These findings therefore demonstrate a new role for MSC in FL, that being to support FL TFH in addition to Treg populations in the tumor microenvironment. MSCs have been shown to support FL B-cell viability and suppress anti-lymphoma T-cell responses. This finding that MSCs support TFH cells, a population that may provide survival signals to FL B-cells, further supports the potential of targeting MSC as a novel therapeutic strategy for patients with FL.
No relevant conflicts of interest to declare.
In a cohort of 1028 children and adolescents infected with human immunodeficiency virus type 1 (HIV-1), the use of combination therapy including protease inhibitors increased from 7 percent in 1996 ...to 73 percent in 1999. Over the four-year period, mortality declined from 5.3 percent to 0.7 percent. This analysis was adjusted for multiple potentially confounding variables; the authors estimate that the use of combination therapy including protease inhibitors in HIV-1–infected children reduces the risk of death by 67 percent.
The use of combination therapy reduces the risk of death by 67 percent.
The combination of human immunodeficiency virus (HIV)–specific protease inhibitors with nucleoside reverse-transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors, or both has been demonstrated in adults to slow the progression of HIV type 1 (HIV-1) disease dramatically and to lower mortality.
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Recent studies provide some evidence of the efficacy and safety of these regimens in children and adolescents,
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but there is only limited evidence of reductions in mortality and morbidity.
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Current guidelines for the treatment of HIV infection in both adults and children recommend combination therapy including protease inhibitors.
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We undertook the present study to estimate the effect of . . .
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