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Breakdown of Bragg-Gray behaviour for low-density detectors under electronic disequilibrium conditions in small megavoltage photon fields. - Physics in medicine and biology
In small photon fields ionisation chambers can exhibit large deviations from Bragg-Gray behaviour; the EGSnrc Monte Carlo (MC) code system has been employed to investigate this 'Bragg-Gray breakdown'. The total electron (+positron) fluence in small water and air cavities in a water phantom has been computed for a full linac beam model as well as for a point source spectrum for 6 MV and 15 MV qualities for field sizes from 0.25â€‰â€‰Ã—â€‰â€‰0.25â€‰cm(2) to 10â€‰â€‰Ã—â€‰â€‰10â€‰cm(2). A water-to-air perturbation factor has been derived as the ratio of total electron (+positron) fluence, integrated over all energies, in a tiny water volume to that in a 'PinPoint 3D-chamber-like' air cavity; for the 0.25â€‰â€‰Ã—â€‰â€‰0.25â€‰cm(2) field size the perturbation factors are 1.323 and 2.139 for 6 MV and 15 MV full linac geometries respectively. For the 15 MV full linac geometry for field sizes of 1â€‰â€‰Ã—â€‰â€‰1â€‰cm(2) and smaller not only the absolute magnitude but also the 'shape' of the total electron fluence spectrum in the air cavity is significantly different to that in the water 'cavity'. The physics of this 'Bragg-Gray breakdown' is fully explained, making reference to the Fano theorem. For the 15 MV full linac geometry in the 0.25â€‰â€‰Ã—â€‰â€‰0.25â€‰cm(2) field the directly computed MC dose ratio, water-to-air, differs by 5% from the product of the Spencer-Attix stopping-power ratio (SPR) and the perturbation factor; this 'difference' is explained by the difference in the shapes of the fluence spectra and is also formulated theoretically. We show that the dimensions of an air-cavity with a perturbation factor within 5% of unity would have to be impractically small in these highly non-equilibrium photon fields. In contrast the dose to water in a 0.25â€‰â€‰Ã—â€‰â€‰0.25â€‰cm(2) field derived by multiplying the dose in the single-crystal diamond dosimeter (SCDDo) by the Spencer-Attix ratio is within 2.9% of the dose computed directly in the water voxel for full linac geometry at both 6 and 15 MV, thereby demonstrating that this detector exhibits quasi Bragg-Gray behaviour over a wide range of field sizes and beam qualities.
Grandparent caregiving among rural African Americans in a community in the American South: challenges to health and wellbeing. - Rural and remote health
An increasing number of grandparents in rural USA are serving as primary caregivers for their grandchildren because of parental incarceration, addiction, joblessness, or illness. Low-income, African American women from the South are overrepresented in this growing population. There is a paucity of research exploring the challenges faced by rural grandparent caregivers, and past studies have not explicitly addressed the potential consequences of rural grandparent caregiving for health. The purpose of this qualitative study was to explore grandparent caregiving among rural, low-income, African American grandmothers in a community in the American South, and to identify challenges to health that arose in that context. McLeroy's social ecological model (SEM) was used to examine these challenges at multiple levels of influence.This qualitative interview-based study was conducted in a high-poverty community in rural Georgia. In-depth interviews were conducted with African American grandparent caregivers and key informants from local community-based organizations. A key informant assisted in identifying initial interview participants, and then snowball sampling was used to recruit additional participants. Interview questions were grouped under five domains (intrapersonal, interpersonal, community, organizational, and policy), according to the levels of the SEM. Iterative content analysis of interview transcripts was utilized. Transcripts were coded to identify text segments related to each domain of the SEM, which were grouped together for analysis by domain. Reflexive memo-writing aided in development of themes, and data quality was assessed using Lincoln and Guba's trustworthiness criteria.Rural African American grandparent caregivers faced a range of challenges to health. Direct physical challenges included chronic pain that interfered with sleep and daily functioning, mobility issues exacerbated by child care, and the pressure of managing their own medical conditions as well as their grandchildren's. Financial scarcity added to their vulnerability to poor health outcomes, especially when caregivers would forego purchase of medications or visits to the doctor because of expenses related to their grandchildren. In addition, lack of child care made health appointments and hospitalizations logistically difficult. Emotional strain was common as grandparent caregivers struggled to protect their grandchildren in communities where rates of drug use, HIV, and incarceration were high. Caregivers worried about their mortality and the related consequences for their grandchildren. Chronic stress, which is linked to a number of poor health outcomes, was self-reported by most rural grandparent caregivers.In this study, the challenges of rural grandparent caregiving among African American women posed multiple threats to health and wellbeing. Further research is needed, in different rural contexts and with different caregiver populations, to more thoroughly examine the health risks of grandparent caregiving. In addition, the development of multi-faceted interventions and programs will be critical to meeting the needs of rural grandparent caregivers. A few models for such programs exist, although resource shortfalls have often limited their impact.
Vascular ring diagnosis following respiratory arrest. - BMJ case reports
Vascular rings can present with non-specific respiratory and/or oesophageal symptoms. Early diagnosis requires a high index of suspicion. This case report describes an uncommon acute presentation of a vascular ring. We report a thriving 14-month-old child with a long history of recurrent wheeze and 'noisy breathing'. He presented acutely with food bolus impaction in the oesophagus which led to a respiratory arrest. Oesophagoscopy and bronchoscopy suggested vascular ring anomaly. A contrast-enhanced CT scan demonstrated a right-sided aortic arch with left ligamentum arteriosum encircling the oesophagus and airway. The ligament was ligated and divided. At follow-up 6â€…months later, the infant had mild persistent stridor but was otherwise well.2014 BMJ Publishing Group Ltd.
Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping. - Health physics
Integral to the characterization of radiation-induced tissue damage is the identification of unique biomarkers. Biomarker discovery is a challenging and complex endeavor requiring both sophisticated experimental design and accessible technology. The resources within the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against Radiological Threats (MCART), allow for leveraging robust animal models with novel molecular imaging techniques. One such imaging technique, MALDI (matrix-assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for the direct spatial visualization of lipids, proteins, small molecules, and drugs/drug metabolites-or biomarkers-in an unbiased manner. MALDI-MSI acquires mass spectra directly from an intact tissue slice in discrete locations across an x, y grid that are then rendered into a spatial distribution map composed of ion mass and intensity. The unique mass signals can be plotted to generate a spatial map of biomarkers that reflects pathology and molecular events. The crucial unanswered questions that can be addressed with MALDI-MSI include identification of biomarkers for radiation damage that reflect the response to radiation dose over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI also enable integration of biomarker identification among diverse animal models. Analysis of early, sublethally irradiated tissue injury samples from diverse mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated with histological features of these unique tissues. This paper will discuss the application of MALDI-MSI for use in a larger biomarker discovery pipeline.
Identification and quantitation of biomarkers for radiation-induced injury via mass spectrometry. - Health physics
Biomarker identification and validation for radiation exposure is a rapidly expanding field encompassing the need for well defined animal models and advanced analytical techniques. The resources within the consortium, Medical Countermeasures Against Radiological Threats (MCART), provide a unique opportunity for accessing well defined animal models that simulate the key sequelae of the acute radiation syndrome and the delayed effects of acute radiation exposure. Likewise, the use of mass spectrometry-based analytical techniques for biomarker discovery and validation enables a robust analytical platform that is amenable to a variety of sample matrices and considered the benchmark for biomolecular identification and quantitation. Herein, the authors demonstrate the use of two targeted mass spectrometry approaches to link established MCART animal models to identified metabolite biomarkers. Circulating citrulline concentration was correlated to gross histological gastrointestinal tissue damage, and retinoic acid production in lung tissue was established to be reduced at early and late time points post high dose irradiation. Going forward, the use of mass spectrometry-based metabolomics coupled to well defined animal models provides the unique opportunity for comprehensive biomarker discovery.
Increased long chain acyl-Coa synthetase activity and fatty acid import is linked to membrane synthesis for development of picornavirus replication organelles. - PLoS pathogens
All positive strand (+RNA) viruses of eukaryotes replicate their genomes in association with membranes. The mechanisms of membrane remodeling in infected cells represent attractive targets for designing future therapeutics, but our understanding of this process is very limited. Elements of autophagy and/or the secretory pathway were proposed to be hijacked for building of picornavirus replication organelles. However, even closely related viruses differ significantly in their requirements for components of these pathways. We demonstrate here that infection with diverse picornaviruses rapidly activates import of long chain fatty acids. While in non-infected cells the imported fatty acids are channeled to lipid droplets, in infected cells the synthesis of neutral lipids is shut down and the fatty acids are utilized in highly up-regulated phosphatidylcholine synthesis. Thus the replication organelles are likely built from de novo synthesized membrane material, rather than from the remodeled pre-existing membranes. We show that activation of fatty acid import is linked to the up-regulation of cellular long chain acyl-CoA synthetase activity and identify the long chain acyl-CoA syntheatse3 (Acsl3) as a novel host factor required for polio replication. Poliovirus protein 2A is required to trigger the activation of import of fatty acids independent of its protease activity. Shift in fatty acid import preferences by infected cells results in synthesis of phosphatidylcholines different from those in uninfected cells, arguing that the viral replication organelles possess unique properties compared to the pre-existing membranes. Our data show how poliovirus can change the overall cellular membrane homeostasis by targeting one critical process. They explain earlier observations of increased phospholipid synthesis in infected cells and suggest a simple model of the structural development of the membranous scaffold of replication complexes of picorna-like viruses, that may be relevant for other (+)RNA viruses as well.
The TLR4 antagonist Eritoran protects mice from lethal influenza infection. - Nature
There is a pressing need to develop alternatives to annual influenza vaccines and antiviral agents licensed for mitigating influenza infection. Previous studies reported that acute lung injury caused by chemical or microbial insults is secondary to the generation of host-derived, oxidized phospholipid that potently stimulates Toll-like receptor 4 (TLR4)-dependent inflammation. Subsequently, we reported that Tlr4(-/-) mice are highly refractory to influenza-induced lethality, and proposed that therapeutic antagonism of TLR4 signalling would protect against influenza-induced acute lung injury. Here we report that therapeutic administration of Eritoran (also known as E5564)-a potent, well-tolerated, synthetic TLR4 antagonist-blocks influenza-induced lethality in mice, as well as lung pathology, clinical symptoms, cytokine and oxidized phospholipid expression, and decreases viral titres. CD14 and TLR2 are also required for Eritoran-mediated protection, and CD14 directly binds Eritoran and inhibits ligand binding to MD2. Thus, Eritoran blockade of TLR signalling represents a novel therapeutic approach for inflammation associated with influenza, and possibly other infections.
Using cavity theory to describe the dependence on detector density of dosimeter response in non-equilibrium small fields. - Physics in medicine and biology
The dose imparted by a small non-equilibrium photon radiation field to the sensitive volume of a detector located within a water phantom depends on the density of the sensitive volume. Here this effect is explained using cavity theory, and analysed using Monte Carlo data calculated for schematically modelled diamond and Pinpoint-type detectors. The combined impact of the density and atomic composition of the sensitive volume on its response is represented as a ratio, Fw,det, of doses absorbed by equal volumes of unit density water and detector material co-located within a unit density water phantom. The impact of density alone is characterized through a similar ratio, PÏ -, of doses absorbed by equal volumes of unit and modified density water. The cavity theory is developed by splitting the dose absorbed by the sensitive volume into two components, imparted by electrons liberated in photon interactions occurring inside and outside the volume. Using this theory a simple model is obtained that links PÏ - to the degree of electronic equilibrium, see, at the centre of a field via a parameter Icav determined by the density and geometry of the sensitive volume. Following the scheme of Bouchard et al (2009 Med. Phys. 36 4654-63) Fw,det can be written as the product of PÏ -, the water-to-detector stopping power ratio [L[overline](Î”)/Ï](w)(det), and an additional factor Pfl -. In small fields [L[overline](Î”)/Ï](w)(det) changes little with field-size; and for the schematic diamond and Pinpoint detectors Pfl - takes values close to one. Consequently most of the field-size variation in Fw,det originates from the PÏ - factor. Relative changes in see and in the phantom scatter factor sp are similar in small fields. For the diamond detector, the variation of PÏ - with see (and thus field-size) is described well by the simple cavity model using an Icav parameter in line with independent Monte Carlo estimates. The model also captures the overall field-size dependence of PÏ - for the schematic Pinpoint detector, again using an Icav value consistent with independent estimates.
Obesity in sub-Saharan Africa: development of an ecological theoretical framework. - Health promotion international
The prevalence of overweight and obesity is increasing in sub-Saharan Africa (SSA). There is a need for theoretical frameworks to catalyze further research and to inform the development of multi-level, context-appropriate interventions. In this commentary, we propose a preliminary ecological theoretical framework to conceptualize factors that contribute to increases in overweight and obesity in SSA. The framework is based on a Causality Continuum model [Coreil et al. Social and Behavioral Foundations of Public Health. Sage Publications, Thousand Oaks] that considers distant, intermediate and proximate influences. The influences incorporated in the model include globalization and urbanization as distant factors; occupation, social relationships, built environment and cultural perceptions of weight as intermediate factors and caloric intake, physical inactivity and genetics as proximate factors. The model illustrates the interaction of factors along a continuum, from the individual to the global marketplace, in shaping trends in overweight and obesity in SSA. The framework will be presented, each influence elucidated and implications for research and intervention development discussed. There is a tremendous need for further research on obesity in SSA. An improved evidence base will serve to validate and develop the proposed framework further.
Characterizing the influence of detector density on dosimeter response in non-equilibrium small photon fields. - Physics in medicine and biology
The impact of density and atomic composition on the dosimetric response of various detectors in small photon radiation fields is characterized using a 'density-correction' factor, F(detector), defined as the ratio of Monte Carlo calculated doses delivered to water and detector voxels located on-axis, 5Â cm deep in a water phantom with a SSD of 100Â cm. The variation of F(detector)Â with field size has been computed for detector voxels of various materials and densities. For ion chambers and solid-state detectors, the well-known variation of F(detector)Â at small field sizes is shown to be due to differences between the densities of detector active volumes and water, rather than differences in atomic number. However, associated changes in the measured shapes of small-field profiles offset these variations in F(detector), so that integral doses measured using the different detectors are quite similar, at least for slit fields. Since changes in F(detector)Â with field size arise primarily from differences between the densities of the detector materials and water, ideal small-field relative dosimeters should have small active volumes and water-like density.
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