Assessment of MIRD data for internal dosimetry using the GATE Monte Carlo code

GATE/GEANT is a Monte Carlo code dedicated to nuclear medicine that allows calculation of the dose to organs of voxel phantoms. On the other hand, MIRD is a well-developed system for estimation of the dose to human organs. In this study, results obtained from GATE/GEANT using Snyder phantom are compared to published MIRD data. For this, the mathematical Snyder phantom was discretized and converted to a digital phantom of 100 × 200 × 360 voxels. The activity was considered uniformly distributed within kidneys, liver, lungs, pancreas, spleen, and adrenals. The GATE/GEANT Monte Carlo code was used to calculate the dose to the organs of the phantom from mono-energetic photons of 10, 15, 20, 30, 50, 100, 200, 500, and 1000 keV. The dose was converted into specific absorbed fraction (SAF) and the results were compared to the corresponding published MIRD data. On average, there was a good correlation (r ²>0.99) between the two series of data. However, the GATE/GEANT data were on average −0.16 ± 6.22% lower than the corresponding MIRD data for self-absorption. Self-absorption in the lungs was considerably higher in the MIRD compared to the GATE/GEANT data, for photon energies of 10–20 keV. As for cross-irradiation to other organs, the GATE/GEANT data were on average +1.5 ± 8.1% higher than the MIRD data, for photon energies of 50–1000 keV. For photon energies of 10–30 keV, the relative difference was +7.5 ± 67%. It turned out that the agreement between the GATE/GEANT and the MIRD data depended upon absolute SAF values and photon energy. For 10–30 keV photons, where the absolute SAF values were small, the uncertainty was high and the effect of cross-section prominent, and there was no agreement between the GATE/GEANT results and the MIRD data. However, for photons of 50–1,000 keV, the bias was negligible and the agreement was acceptable.     

The adult male voxel model "Golem" segmented from whole-body CT patient data

This paper describes the construction of an adult male voxel model named ”Golem”¹(¹In Jewish tradition, Golem (Hebrew: shapeless matter) means an artificial human being endowed with life. There are several legends about successful creations of the Golem. The most popular one is probably the Golem of Prague, created (and destroyed) by Rabbi Yehuda Loev (1525–1609).) intended to be used for Monte Carlo simulations to calculate dosimetric quantities for radiation protection considerations. The model was segmented from whole-body medical image data of a living person who was 38 years old and had external dimensions close to those of the ICRP Reference Man. The segmentation process using dedicated image processing hard- and software is described and the resulting model is characterised with respect to weight and height of the total body, organ and tissue masses and red bone marrow distribution. A comparison with the respective data for ICRP Reference Man and three further voxel models is presented. Golem was found to agree reasonably well with Reference Man, so that he can be used for the assessment of ”representative” body doses. Received: 9 October 2000 / Accepted: 29 January 2001     

The construction of computer tomographic phantoms and their application in radiology and radiation protection

Summary In order to assess human organ doses for risk estimates under natural and man made radiation exposure conditions, human phantoms have to be used. As an improvement to the mathematical anthropomorphic phantoms, a new family of phantoms is proposed, constructed from computer tomographic (CT) data. A technique is developed which allows any physical phantom to be converted into computer files to be used for several applications. The new human phantoms present advantages towards the location and shape of the organs, in particular the hard bone and bone marrow. The CT phantoms were used to construct three dimensional images of high resolution; some examples are given and their potential is discussed. The use of CT phantoms is also demonstrated to assess accurately the proportion of bone marrow in the skeleton. Finally, the use of CT phantoms for Monte Carlo (MC) calculations of doses resulting from various photon exposures in radiology and radiation protection is discussed.Dedicated to Prof. W. Jacobi on the occasion of his 60th birthday     

A mathematical model of the optokinetic reflex

The role of the optokinetic reflex (OKR) is that of cooperating with the vestibulo-ocular reflex (VOR) in the task of image stabilization on the retina during head rotations in a stationary visual surround. Since the dynamics of VOR was already well established, it has been possible to make a broad estimation of what the dynamics of OKR should be in order to obtain the performances observed in normal subjects. A mathematical model of OKR has been presented, and the experimental results obtained by Raphan et al. (1977) in the monkey and by Collins et al. (1970) in man were used to validate the model and to obtain a precise estimation of its parameters.Work supported by CNR, Special Project on Biomedical Engineering, grant No. 78.00512.86     

A non-linear model for visual-vestibular interaction during body rotation in man

A mathematical model for visual-vestibular interaction during body rotation in an illuminated visual surround is obtained by combining a previous model of the optokinetic reflex (OKR) with a simplified model of the vestibulo-ocular reflex (VOR). OKR is activated by the slip of the image of the external world on the retina, and represents a negative feedback loop around VOR. For large retinal slip velocities OKR behaves as a basically non-linear system. The validity of the model is proved via computer simulation by comparing predicted responses with the experimental results obtained in man by Koenig et al. (1978) in different situations of visual-vestibular interaction.Work supported by C.N.R. (Rome, Italy), Special Project on Piomedical Engineering, Grant No. 79.01255.86     

Do large dogs die young?

In most animal taxa, longevity increases with body size across species, as predicted by the oxidative stress theory of aging. In contrast, in within-species comparisons of mammals and especially domestic dogs (e.g. Patronek et al., '97; Michell, '99; Egenvall et al., 2000; Speakman et al., 2003), longevity decreases with body size.We explore two datasets for dogs and find support for a negative relationship between size and longevity if we consider variation across breeds. Within breeds, however, the relationship is not negative and is slightly, but significantly, positive in the larger of the two datasets. The negative across-breed relationship is probably the consequence of short life spans in large breeds. Artificial selection for extremely high growth rates in large breeds appears to have led to developmental diseases that seriously diminish longevity.     

Data for the Reference Man: skeleton content of chemical elements

This study was undertaken to provide reference values of chemical element mass fractions in intact bone of Reference (European Caucasian) Man/Woman. The rib bone samples investigated were obtained from autopsies of 84 apparently healthy 15–58-year-old citizens (38 females and 46 males) of a non-industrial region in the Central European part of Russia who had suffered sudden death. The mass fractions (mg/kg given on a wet mass basis) of 69 elements in these bone samples were measured by using neutron activation analysis with high-resolution spectrometry of short-lived and long-lived radionuclides, particle-induced gamma-ray emission, inductively coupled plasma atomic emission spectrometry, and inductively coupled plasma mass spectrometry including necessary quality control measures. Using published and measured data, mass fraction values of the 79 elements for the rib bone have been derived. Based on accepted rib to skeleton mass fractions and reference values of skeleton mass for Reference Man, the elemental burdens in the skeleton were estimated. These results may provide a representative bases for establishing related reference values for the Russian Reference Man/Woman and for revising and adding current reference values for the International Commission on Radiological Protection. The data presented will also be very valuable for many other applications in radiation protection, radiotherapy radiation dosimetry, and other scientific fields.     

Immunohistochemical verification of kisspeptins and their receptor in human fetal organs during prenatal development

Kisspeptins (KPs) and their receptor (KISS1R) play an important role in many physiological processes in the body, such as sexual maturation, reproductive system functioning, placentation, insulin secretion, and vasoconstriction. The highest level of kisspeptins and their receptor is observed in the organs of hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes, both in the form of mRNA and peptide. Kisspeptins are found in various body tissues: spinal cord (Dun et al., 2003), pancreas (Song et al., 2014), esophagus (Kostakis et al., 2013), adrenal glands and secretory system organs (Wahab et al., 2015), and in malignancies (Lee and Welch, 1997). However, the localization and the role of kisspeptins and their receptor in organs during fetal development have not yet been studied. At the same time, ample published data regarding the localization of kisspeptins and their receptors in human organs and tissues are discrepant, which requires the development of a standard staining technique. The modified technique presented in this paper made it possible to identify and evaluate the expression of kisspeptins and their receptor in human fetal organs at different stages of development. Kisspeptins and their receptors were found in all organs and tissues examined by us, but the degree of reaction was different. The highest level was observed in the hypothalamus material in the 28–32-week period, and the lowest amount of the protein was detected in the uterine material at all stages. Maximum level of KISS1R was detected in the pituitary material in the 36–40-week period. A correlation between gestational age and the level of kisspeptins in the ovaries, uterus, and adrenal glands was found: a significant increase in the amount of protein was detected. A significant increase in the amount of the kisspeptin receptor in pituitary, ovary, and uterus material was shown.     

Clastogenic effects of acrylamide in mouse bone marrow cells

Acrylamide, known to induce dominant-lethal mutations (Shelby et al., 1986; Smith et al., 1986) and heritable translocations (Shelby et al., 1987) in rodent germ cells, was hitherto a questionable clastogen in rodent bone marrow (Shiraishi, 1978). Therefore, it was tested for chromosomal aberrations in mouse bone marrow cells, spermatogonia and by the micronucleus test. The intraperitoneally injected doses ranged from 50 to 150 mg/kg. In the chromosomal bone marrow test and the micronucleus assay positive results were obtained with acrylamide, and in the latter test the effect increased linearly with dose. Chromosomal aberrations were not induced in differentiating spermatogonia by the acute acrylamide treatment. Cisplatin was used as a positive control and gave the expected positive response in all 3 tests. The present results demonstrate that acrylamide is no exception among clastogens. It breaks chromosomes not only in mammalian germ cells but also in somatic cells.     

New neurons maintain efficient stress recovery

Adult neurogenesis has been the focus of intense investigation, but the function of new neurons remains elusive. Snyder et?al. (2011) report that new neurons in the hippocampus play an important role in appropriate shut-off of the stress response.     

The structure of sugar chains of Japanese quail ovomucoid. The occurrence of oligosaccharides not expected from the classical biosynthetic pathway for N-glycans; a method for the assessment of the structure of glycans present in picomolar amounts

While the structure of the major oligosaccharide of Japanese quail ovomucoid was reported earlier (Hase, S. et al. (1982) J. Biochem. 91, 735-737), the structures of the minor oligosaccharide units were investigated for the first time in the present studies. For this purpose, the glycans of the protein were liberated from the polypeptide chain by hydrazinolysis. After N-acetylation, the reducing ends of the oligosaccharides obtained were coupled with 2-aminopyridine, and then the resulting fluorescent derivatives were purified by Bio-Gel P-2 column chromatography and reversed-phase HPLC. The chemical structures of two minor oligosaccharide units were determined with the aid of exoglycosidases, and by methylation analysis and Smith degradation. The results demonstrated that the ovomucoid contains the following two monoantennary glycans: Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc and Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc. The latter structure was not predicted by the classical metabolic pathway for the N-glycans to be formed. The structures of three additional minor heterosaccharides were deduced from their elution positions on HPLC together with the results of determination of their molecular sizes and the HPLC elution positions of their enzymatic degradation products. It is noteworthy that for the latter procedure for the estimation of the structures of oligosaccharides only minute quantities of glycans (several hundreds pmol) are required.     

Association between resistance to Bt cotton and cadherin genotype in pink bollworm

Two strains of pink bollworm, Pectinophora gossypiella (Saunders), each derived in 1997 from a different field population, were selected for resistance to Bacillus thuringiensis (Bt) toxin Cry1Ac in the laboratory. One strain (MOV97-R) originated from Mohave Valley in western Arizona; the other strain (SAF97-R) was from Safford in eastern Arizona. Relative to a susceptible laboratory strain, Cry1Ac resistance ratios were 1700 for MOV97-R and 520 for SAF97-R. For the two resistant strains, larval survival did not differ between non-Bt cotton and transgenic cotton producing CrylAc. In contrast, larval survival on Bt cotton was 0% for the two unselected parent strains from which the resistant strains were derived. Previously identified resistance (r) alleles of a cadherin gene (BtR) occurred in both resistant strains: r1 and r3 in MOV97-R, and r1 and r2 in SAF97-R. The frequency of individuals carrying two r alleles (rr) was 1.0 in the two resistant strains and 0.02 in each of the two unselected parent strains. Furthermore, in two hybrid strains with a mixture of susceptible (s) and r alleles at the BtR locus, all survivors on Bt cotton had two r alleles. The results show that resistance to Cry1Ac-producing Bt cotton is associated with recessive r alleles at the BtR locus in the strains of pink bollworm tested here. In conjunction with previous results from two other Bt-resistant strains of pink bollworm (APHIS-98R and AZP-R), results reported here identify the cadherin locus as the leading candidate for molecular monitoring of pink bollworm resistance to Bt cotton.     

A revisit on tests for homogeneity of the risk difference

Lipsitz et al. (1998, Biometrics 54, 148-160) discussed testing the homogeneity of the risk difference for a series of 2 x 2 tables. They proposed and evaluated several weighted test statistics, including the commonly used weighted least squares test statistic. Here we suggest various important improvements on these test statistics. First, we propose using the one-sided analogues of the test procedures proposed by Lipsitz et al. because we should only reject the null hypothesis of homogeneity when the variation of the estimated risk differences between centers is large. Second, we generalize their study by redesigning the simulations to include the situations considered by Lipsitz et al. (1998) as special cases. Third, we consider a logarithmic transformation of the weighted least squares test statistic to improve the normal approximation of its sampling distribution. On the basis of Monte Carlo simulations, we note that, as long as the mean treatment group size per table is moderate or large (> or = 16), this simple test statistic, in conjunction with the commonly used adjustment procedure for sparse data, can be useful when the number of 2 x 2 tables is small or moderate (< or = 32). In these situations, in fact, we find that our proposed method generally outperforms all the statistics considered by Lipsitz et al. Finally, we include a general guideline about which test statistic should be used in a variety of situations.     

Scale-Adjusted Metrics for Predicting the Evolution of Urban Indicators and Quantifying the Performance of Cities

More than a half of world population is now living in cities and this number is expected to be two-thirds by 2050. Fostered by the relevancy of a scientific characterization of cities and for the availability of an unprecedented amount of data, academics have recently immersed in this topic and one of the most striking and universal finding was the discovery of robust allometric scaling laws between several urban indicators and the population size. Despite that, most governmental reports and several academic works still ignore these nonlinearities by often analyzing the raw or the per capita value of urban indicators, a practice that actually makes the urban metrics biased towards small or large cities depending on whether we have super or sublinear allometries. By following the ideas of Bettencourt et al. [PLoS ONE 5 (2010) e13541], we account for this bias by evaluating the difference between the actual value of an urban indicator and the value expected by the allometry with the population size. We show that this scale-adjusted metric provides a more appropriate/informative summary of the evolution of urban indicators and reveals patterns that do not appear in the evolution of per capita values of indicators obtained from Brazilian cities. We also show that these scale-adjusted metrics are strongly correlated with their past values by a linear correspondence and that they also display crosscorrelations among themselves. Simple linear models account for 31%–97% of the observed variance in data and correctly reproduce the average of the scale-adjusted metric when grouping the cities in above and below the allometric laws. We further employ these models to forecast future values of urban indicators and, by visualizing the predicted changes, we verify the emergence of spatial clusters characterized by regions of the Brazilian territory where we expect an increase or a decrease in the values of urban indicators.     

Three-dimensional trabecular alignment model

Trabecular alignment theory has been used to quantify Wolff's Law of bone remodeling. A three-dimensional finite element scheme was developed to analyze the bone remodeling phenomenon. The mathematical model proposed by Mullender et al. and later modified by Smith et al. was adopted to simulate the surface-based trabecular resorption and formation processes. Enhancements incorporated into the previous model include: mapping into three-dimensions, controlling the remodeling signal's passage through marrow, controlling the finite distance the signal may pass through the bone matrix, and including non-bone material in the finite element model. After the model is explained and thoroughly studied, three-dimensional implant surface geometries are simulated.     

Trypanosoma (Megatrypanum) saloboense n. sp. (Kinetoplastida: Trypanosomatidae) parasite of Monodelphis emiliae (Marsupiala: Didelphidae) from Amazonian Brazil

Trypanosoma (Megatrypanum) soloboense n. sp., is described in the Brazilian opossum Monodelphis emiliae (Thomas, 1912) from primary forest in the Salobo area of the Serra dos Carajás (6 degrees S, 50 degrees 18' W) Pará State, North Brazil. Two morphologically different trypomastigotes were noted. Slender forms, regarded as immature parasites, have a poorly developed undulating membrane adhering closely to the body: large, broad forms with a well developed membrane are considered to be the mature trypomastigotes and have a mean total length of 71.2 microm (62.4-76.2) and a width of 6.1 (5.0-8.0). Infections studied in two opossums were of very low parasitaemia. The large size of T. (M.) saloboense readily distinguishes it from the two previously described members of the subgenus Megatrypanum of neotropical marsupials, T. (M.) freitasi Régo et al., 1957 of Didelphis ozarae and D. marsupialis, and T. (M.) samueli Mello, 1977 of Monodelphis domesticus, which measure only 49.0-51.5 microm and 42.4 microm respectively. No infections were obtained in hamsters inoculated with triturated liver and spleen from one infected M. emiliae, or in laboratory mice inoculated with epimastigotes from a blood-agar culture. No division stages could be detected in the internal organs or the peripheral blood.     

Structural studies of urinary oliogosaccharides from patients with mannosidosis

Eight neutral oligosaccharide fractions were obtained from the pooled urine of two patients with mannosidosis by Bio-Gel P2 and Bio-Gel P4 column chromatography. The structures of seventeen oligosaccharides were determined by monosaccharide composition analysis, methylation studies, acetolysis, Smith degradation, and ¹³C NMR analysis. Three of the proposed structures, Manα1-3Manβ1-4GlcNAc, Manα1-2Manα1-3Manβ1-4GlcNAc, and Manα1-2Manα1-2Manα1-3Manβ1-4GlcNAc are identical to those first published by Norden et al. (N. E. Norden, A. Lundblad, S. Svennson, P. A. Ockerman, and S. Autio, 1973. J. Biol. Chem.248, 6210–6215; N. E. Norden, A. Lundblad, S. Svennson, and S. Autio, 1974. Biochemistry13, 871–874). Thirteen of them, Manα1-3Manα1-6(Manα1-3)-Manβ1-4GlcNAc, Manα1-3Manα1-6(Manα1-2Manα1-3)Manβ1-4GlcNAc, and 11 isomers of (Manα1-2)_0–4[Manα1-6(Manα1-3)Manα1-6(Manα1-3)Manβ1-4GlcNAc], are the same as those first published by Yamashita et al. (K. Yamashita, Y. Tachibana, K. Mihara, S. Okada, H. Yabuuchi, and A. Kobata, 1980, J. Biol. Chem.255, 5126–5133); a tetrasac-charide, Manα1-6(Manα1-3)Manβ1-4GlcNAc, is newly reported and several other structural possibilities are proposed.     

Mathematical and experimental analyses of antibody transport in hollow-fiber-based specific antibody filters

We are developing hollow fiber-based specific antibody filters (SAFs) that selectively remove antibodies of a given specificity directly from whole blood, without separation of the plasma and cellular blood components and with minimal removal of plasma proteins other than the targeted pathogenic antibodies. A principal goal of our research is to identify the primary mechanisms that control antibody transport within the SAF and to use this information to guide the choice of design and operational parameters that maximize the SAF-based antibody removal rate. In this study, we formulated a simple mathematical model of SAF-based antibody removal and performed in vitro antibody removal experiments to test key predictions of the model. Our model revealed three antibody transport regimes, defined by the magnitude of the Damk?hler number Da (characteristic antibody-binding rate/characteristic antibody diffusion rate): reaction-limited (Da /= 10). For a given SAF geometry, blood flow rate, and antibody diffusivity, the highest antibody removal rate was predicted for diffusion-limited antibody transport. Additionally, for diffusion-limited antibody transport the predicted antibody removal rate was independent of the antibody-binding rate and hence was the same for any antibody-antigen system and for any patient within one antibody-antigen system. Using SAF prototypes containing immobilized bovine serum albumin (BSA), we measured anti-BSA removal rates consistent with transport in the intermediate regime (Da approximately 3). We concluded that initial SAF development work should focus on achieving diffusion-limited antibody transport by maximizing the SAF antibody-binding capacity (hence maximizing the characteristic antibody-binding rate). If diffusion-limited antibody transport is achieved, the antibody removal rate may be raised further by increasing the number and length of the SAF fibers and by increasing the blood flow rate through the SAF.