Intensity modulated radiation therapy can be achieved by driving the leaves of a multileaf collimator (MLC) across an x-ray therapy beam. Algorithms to generate the required leaf trajectories assume ...that the leaf positions are exactly known to the MLC controller. In practice, leaf positions depend upon calibration accuracy and stability and may vary within set tolerances. The purpose of this study was to determine the effects of potential leaf position inaccuracies on intensity modulated beams. Equations are derived which quantify the absolute error in delivered monitor units given a known error in leaf position. The equations have been verified by ionization chamber measurements in dynamically delivered flat fields, comparing deliveries in which known displacements have been applied to the defined leaf positions with deliveries without displacements applied. The equations are then applied to two clinical intensity modulations: an inverse planned prostate field and a breast compensating field. It is shown that leaf position accuracy is more critical for a highly modulated low-dose intensity profile than a moderately modulated high-dose intensity profile. Suggestions are given regarding the implications for quality control of dynamic MLC treatments.
Background: Previous studies of the relation between age and body fat reached differing conclusions concerning the question of whether body fat is lower in the elderly than in middle-aged persons. ...Objective: The objectives of this study were to characterize the relation between age and body fat in 4 ethnic groups and test the hypothesis that body fat is lower in the elderly than in middle-aged persons. Design: Body fat was measured in a sample of 1324 volunteers aged 20-94 y by using a 4-component model of body composition. Four ethnic groups were studied: Asians, blacks, Puerto Ricans, and whites. Regression models were developed for fat mass and fat percentage as functions of age. Results: In all but one of the groups, a highly significant curvilinear relation between age and body fat was found, indicating a peak amount of body fat in late middle age and lower amounts of body fat at younger and older ages (P < 0.001). The age at which maximum body fat was predicted in the various groups ranged from 53 to 61 y for fat mass and from 55 to 71 y for fat percentage. In Puerto Rican men there was no significant relation between age and fat mass, and the relation between age and fat percentage was linear and positively correlated. Conclusions: This study provided data on the relation between age and body fat in 4 ethnic groups and supported the hypothesis that body fat is lower in the elderly than in middle-aged persons.
Nonenzymatic glycation of type IV collagen and matrix metalloproteinase susceptibility. The glomerular basement membrane (GBM) is damaged in diabetes through complex mechanisms that are not fully ...understood. Prominent among them is nonenzymatic protein glycation leading to the formation of so-called advanced glycation end products (AGEs). We examined the effects of in vitro glycation of intact collagen type IV in bovine lens capsule (LBM) and kidney glomerular (GBM) basement membranes on their susceptibility to matrix metalloproteinases, using stromelysin 1 (MMP-3) and gelatinase B (MMP-9). Sites of cleavage of unmodified LBM collagen were located in the triple helical region. In vitro glycation by glucose severely inhibited the release of soluble collagen cleavage peptides by MMP-3 and MMP-9. The distribution of AGEs within the three domains of collagen IV (7S, triple helical, and non-collagenous NC1) were compared for LBM glycation using AGE fluorescence, pentosidine quantitation, and immunoreactivity towards anti-AGE antibodies that recognize the AGE carboxymethyllysine (CML). Marked asymmetry was observed, with the flexible triple helical domain having the most pentosidine and fluorescent AGEs but the least CML. The in vivo relevance of these findings is supported by preliminary studies of AGE distribution in renal basement membrane (RBM) collagen IV domains from human kidneys of two insulin-dependent diabetics and one normal subject. Pentosidine and fluorescent AGE distributions of diabetic RBM were similar to LBM, but the CML AGE in diabetic kidney was less in the triple helical domain than in NCI. Our results support the hypothesis that nonenzymatic glycation of collagen IV contributes to the thickening of basement membranes, a hallmark of diabetic nephropathy.
The CHARMM22 force field with associated partial charges is used to calculate the infrared spectra of a number of small proteins and some larger biothreat proteins. The calculated high-frequency ...region, from about 2,500 to 3,500 cm
−1
, is dominated by stretching modes of hydrogen bonded to other atoms, and is very similar in all proteins. There is a peak at 3,430 cm
−1
whose intensity is predicted by these calculations to be a direct measure of arginine content. The calculated low-frequency THz region, up to 300 cm
−1
, is also very similar in all the proteins and just reflects the vibrational density of states in agreement with experimental results. Calculations show that the intermediate-frequency region between 500 and 1,200 cm
−1
shows the greatest difference between individual proteins and is also the least affected by water absorption. However, to match experimental measurements in the amide region, it was necessary to reduce the hydrogen partial charges.
Mice expressing an error-prone mitochondrial DNA polymerase rapidly accumulate random mutations in mitochondrial DNA. Expression of the transgene in the heart leads to dilated cardiomyopathy ...accompanied by a wave of apoptosis in cardiomyocytes, and a vigorous and persistent protective response, including upregulation of the anti-apoptotic protein, Bcl-2. To investigate the role of the mitochondrial permeability transition pore in the development of disease, we treated mice with cyclosporin A (CsA), an inhibitor of pore opening. Drug treatment prevented cardiac dilatation, transgene-specific apoptosis, and upregulation of Bcl-2. It also rescued hearts from the profound decrease in connexin 43, which characterizes the dilatated heart. Treatment with FK506, which like CsA inhibits cytoplasmic calcineurin but not the mitochondrial pore, did not affect disease development, suggesting that the relevant target of CsA was the mitochondrial pore. These data implicate breakdowns in the mitochondrial permeability barrier in pathogenesis of elevated frequencies of mtDNA mutations.
Drawing on ancient texts and modern interpretations, this work explores the foundations for war in China's strategic culture Shih, Li and Tao. The work uses Shih theory to explain the anomalies that ...continue to perplex Euro- American observers in modern China's uses of force.
Introduction
Carer quality of life (QoL) can be included in economic evaluations and captured using EQ-5D. Traditional valuation tasks require participants to imagine living in a health state for a ...number of years, without being told what to consider. This pilot study sought to investigate whether participants implicitly consider the impact of the health state on others, and the extent to which this may impact health state valuations.
Methods
Composite time trade-off (TTO) interviews were conducted with a convenience sample. Each interview included a ‘traditional’ TTO exercise to value three health states, and a ‘combined’ TTO exercise, where participants valued the same health states again, having been informed that they would require a carer living in a particular health state. Qualitative feedback was collected after each exercise. Paired
t
-test comparisons of the utilities elicited in each exercise were made.
Results
Thirty-three participants enrolled in the pilot. Mean differences between exercises were not statistically significant and differed in direction, although considerable heterogeneity was observed in individual response trajectories. Overall, 36% (
n
= 12) of participants expressed an unprompted concern about being a burden on others in the traditional exercise, and 67% (
n
= 22) of participants would have responded differently had the carer been in full health in the combined exercise.
Conclusion
Providing contextual information about carers may impact valuations. Further research is required to better understand the reasons behind the variation in individual response trajectories observed in this pilot study. The insights from this study may be useful for informing the design of related future studies.
Intensity-modulated radiotherapy (IMRT) is increasingly being used to treat head and neck cancer cases.
We discuss the clinical challenges associated with the setting up of an image guided intensity ...modulated radiotherapy service for a subset of head and neck cancer patients, using a recently commissioned helical tomotherapy (HT) Hi Art (Tomotherapy Inc, WI) machine in this article. We also discuss the clinical aspects of the tomotherapy planning process, treatment and image guidance experiences for the first 10 head and neck cancer cases. The concepts of geographical miss along with tomotherapy-specific effects, including that of field width and megavoltage CT (MVCT) imaging strategy, have been highlighted using the first 10 head and neck cases treated.
There is a need for effective streamlining of all aspects of the service to ensure compliance with cancer waiting time targets. We discuss how patient toxicity audits are crucial to guide refinement of the newly set-up planning dose constraints.
This article highlights the important clinical issues one must consider when setting up a head and neck IMRT, image-guided radiotherapy service. It shares some of the clinical challenges we have faced during the setting up of a tomotherapy service. Implementation of a clinical tomotherapy service requires a multidisciplinary team approach and relies heavily on good team working and effective communication between different staff groups.
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