Evaluation of uncertainties in lung measurement of actinides due to non-uniform distribution of activity in lungs.

Various parameters can introduce uncertainties in the lung activity measurements of actinides. In this study, uncertainties due to non-uniform distribution of activity in the lungs are evaluated. To study the effect of non-uniform distribution, lungs of ICRP male thorax voxel and resized phantoms are divided into upper and lower parts of both right and left lungs as well as into anterior and posterior lung regions. Simulation of uniform and non-uniform distribution of activity in lungs is carried out using thorax voxel phantoms in FLUKA for Phoswich and an array of three HPGe detectors for 18-238keV photons. Source sampling for non-uniform distribution of activity is carried out by selecting the source points by varying the weightage to 0.4, 0.5, 0.6 and 1 in different parts of lungs. Uncertainties in lung activity estimation at different energies are quantified in the form of scattering factors (SFs) which are geometric standard deviations. The SFs due to non-uniform distribution of activity of the order of 0.4-0.6 in different parts of the lungs are found to be ~ 1.25 for Phoswich and HPGe array detectors above 18keV.

An anatomical subunit-based outcome assessment scale for bilateral cleft lip and palate.

As there is currently no internationally accepted outcome measurement tool available for complete bilateral cleft lip and palate (CBCLP), the goal of this prospective study was to develop a numerical evaluation scale that allows reliable scoring of this cleft deformity. Our cohort comprised 121 Indian subjects with CBCLP who underwent surgical repair (mean age at time of surgery 6.53 months) using a modified Millard technique. A panel of three professionals evaluated each subject's outcome of bilateral cleft lip repair 6 months postoperatively on two-dimensional (2D) full-face photographs in the frontal view and worm's eye view. A simple two-point rating system was applied to separately analyse a total of 12 components of lip, nose, and scar. The results and mean scores for the analysed anatomical areas were 2.2±1.01 (max=3) for nose, 5.4±1.54 (max=8) for lip, and 1.9±1.3 (max=3) for scar, with a total score 7.7±2.21 (max=12) indicating a good surgical outcome. The inter-examiner ICC for nose, lip, scar, and total score was calculated at 0.836, 0.889, 0.723, and 0.927 respectively and indicated a strong level of repeatability and reliability that was highly significant (P<0.001). In conclusion, we were able to develop and test a scoring system for measuring outcomes in CBCLP that warrants simplicity of use, reliability and reproducibility.

METHODOLOGY FOR THE ASSESSMENT OF INGESTED ACTINIDES FROM MONTE CARLO SIMULATION OF VOXEL PHANTOM.

In case of internal contamination of actinides by ingestion pathway, activity will be transferred to various regions of the alimentary tract over a period of time. In this article, counting efficiencies (CEs) of Phoswich and an array of HPGe detectors are estimated for source in alimentary tract of voxel phantom. The phantom as well as Phoswich, and an array of three HPGe detectors are incorporated in Monte Carlo code 'FLUKA'. Human alimentary tract model is solved using default parameters to identify different compartments where activity will accumulate after an ingestion intake of 1 Bq as a function of time. Accordingly, CEs are evaluated on 0.5-5 d post ingestion intake for the source distributed in the contents of alimentary tract for photon energies in 18-238 keV range representing sources of actinides. The assessment of ingested activity of actinides from abdomen measurements is discussed. Higher CEs are observed with Phoswich detector compared with HPGe array due to its large size and high effective Z. Also, the CEs observed on Days 1-5 using both the detectors are found to decrease by 16-75 % with respect to the CE on half day. Thus, there is need to use CEs according to the observed activity distribution post ingestion intake. The contribution in the abdomen measurements due to source in the lungs and vice versa is also studied for intake by both inhalation and ingestion pathways. The contribution of source in the liver is found to be ∼30-50 % in chest and 75 % in abdomen measurements.

Assessment of uncertainties in the lung activity measurement of low-energy photon emitters using Monte Carlo simulation of ICRP male thorax voxel phantom.

Assessment of intake due to long-lived actinides by inhalation pathway is carried out by lung monitoring of the radiation workers inside totally shielded steel room using sensitive detection systems such as Phoswich and an array of HPGe detectors. In this paper, uncertainties in the lung activity estimation due to positional errors, chest wall thickness (CWT) and detector background variation are evaluated. First, calibration factors (CFs) of Phoswich and an array of three HPGe detectors are estimated by incorporating ICRP male thorax voxel phantom and detectors in Monte Carlo code 'FLUKA'. CFs are estimated for the uniform source distribution in lungs of the phantom for various photon energies. The variation in the CFs for positional errors of ±0.5, 1 and 1.5 cm in horizontal and vertical direction along the chest are studied. The positional errors are also evaluated by resizing the voxel phantom. Combined uncertainties are estimated at different energies using the uncertainties due to CWT, detector positioning, detector background variation of an uncontaminated adult person and counting statistics in the form of scattering factors (SFs). SFs are found to decrease with increase in energy. With HPGe array, highest SF of 1.84 is found at 18 keV. It reduces to 1.36 at 238 keV.

Monte Carlo simulation of skull and knee voxel phantoms for the assessment of skeletal burden of low-energy photon emitters.

In case of internal contamination due to long-lived actinides by inhalation or injection pathway, a major portion of activity will be deposited in the skeleton and liver over a period of time. In this study, calibration factors (CFs) of Phoswich and an array of HPGe detectors are estimated using skull and knee voxel phantoms. These phantoms are generated from International Commission of Radiation Protection reference male voxel phantom. The phantoms as well as 20 cm diameter phoswich, having 1.2 cm thick NaI (Tl) primary and 5cm thick CsI (Tl) secondary detector and an array of three HPGe detectors (each of diameter of 7 cm and thickness of 2.5 cm) are incorporated in Monte Carlo code 'FLUKA'. Biokinetic models of Pu, Am, U and Th are solved using default parameters to identify different parts of the skeleton where activity will accumulate after an inhalation intake of 1 Bq. Accordingly, CFs are evaluated for the uniform source distribution in trabecular bone and bone marrow (TBBM), cortical bone (CB) as well as in both TBBM and CB regions for photon energies of 18, 60, 63, 74, 93, 185 and 238 keV describing sources of (239)Pu, (241)Am, (238)U, (235)U and (232)Th. The CFs are also evaluated for non-uniform distribution of activity in TBBM and CB regions. The variation in the CFs for source distributed in different regions of the bones is studied. The assessment of skeletal activity of actinides from skull and knee activity measurements is discussed along with the errors.

Counting efficiency of whole-body monitoring system using BOMAB and ANSI/IAEA thyroid phantom due to internal contamination of 131I.

In this study, the effect of Indian reference BOttle MAnnikin aBsorber (BOMAB) neck with axial cavity and American National Standards Institute (ANSI)/International Atomic Energy Agency (IAEA) thyroid phantom using pencil sources of (133)Ba ((131)I simulant) on counting efficiency (CE) is seen experimentally in static geometry for whole-body monitoring system comprising 10.16-cm diameter and 7.62-cm-thick NaI(Tl) detector. The CE estimated using the neck part of BOMAB phantom is 50.2% lower in comparison with ANSI phantom. In rest of the studies FLUKA code is used for Monte Carlo simulations using ANSI/IAEA thyroid phantom. The simulation results are validated in static geometries with experimental CE and the differences are within 1.3%. It is observed that CE for pencil source distribution is 3.97% higher for (133)Ba in comparison with CE of (131)I source. Simulated CE for pencil source distribution is 4.7% lower in comparison with uniform source distribution in the volume of thyroid for (131)I. Since the radiation workers are of different physique; overlying tissue thickness (OTT) and neck-to-detector distance play an important role in the calculation of activity in thyroid. The CE decreases with increase in OTT and is found to be 5.5% lower if OTT is changed from 1.1 to 2 cm. Finally, the simulations are carried out to estimate the variation in CE due to variation in the neck-to-detector distance. The CE is 6.2% higher if the neck surface-to-detector distance is decreased from 21.4 to 20.4 cm and it goes on increasing up to 61.9% if the distance is decreased to 15.4 cm. In conclusion, the calibration of whole-body monitoring system for (131)I should be carried out with ANSI/IAEA thyroid phantom, the neck-to-detector distance controlled or the CE corrected for this, and the CE should be corrected for OTT.

Assessment of intravenous pbi-shRNA PDX1 nanoparticle (OFHIRNA-PDX1) in yucatan swine.

PDX1 (pancreatic and duodenal homeobox 1) is overexpressed in pancreatic cancer, and its reduction results in tumor regression. Bi-functional pbi-shRNA PDX1 nanoparticle (OFHIRNA-PDX1) utilizes the endogenous micro-RNA biogenesis pathway to effect cleavage- and non-cleavage-dependent degradation of PDX1 mRNA. We have shown that OFHIRNA-PDX1 reduces pancreatic tumor volume in xenograft models. Thus, we are now exploring biorelevant large animal safety of OFHIRNA-PDX1. Mini pigs were chosen as the biorelevant species based on the similarity of human and pig PDX1 target sequence. In the initial study, animals developed fever, lethargy, hyporexia and cutaneous hyperemia following administration of OFHIRNA-PDX1. Twenty-one days later, the same animals demonstrated less toxicity with a second OFHIRNA-PDX1 infusion in conjunction with a prophylactic regimen involving dexamethasone, diphenhydramine, Indocin and ranitidine. In a new group of animals, PDX1 protein (31 kDa) expression in the pancreas was significantly repressed at 48 and 72 h (85%, P=0.018 and 88%, P=0.013; respectively) following a single infusion of OFHIRNA-PDX1 but recovered to normal state within 7 days. In conclusion, a single intravenous infusion of OFHIRNA-PDX1 in conjunction with premedication in pigs was well tolerated and demonstrated significant PDX1 knockdown.

Monte Carlo simulation of NaI(TL) detector in a shadow-shield scanning bed whole-body monitor for uniform and axial cavity activity distribution in a BOMAB phantom.

This study presents the simulation results for 10.16 cm diameter and 7.62 cm thickness NaI(Tl) detector response, which is housed in a partially shielded scanning bed whole-body monitor (WBM), due to activity distributed in the axial cavities provided in the Indian reference BOMAB phantom. Experimental detection efficiency (DE) for axial cavity activity distribution (ACAD) in this phantom for photon emissions of (133)Ba, (137)Cs and (60)Co is used to validate DEs estimated using Monte Carlo code FLUKA. Simulations are also carried out to estimate DEs due to uniform activity distribution (UAD) as in the standard BOMAB phantom. The results show that the DE is ∼3.8 % higher for UAD when compared with ACAD in the case of (40)K (1460 keV) and this relative difference increases to ∼7.0 % for (133)Ba (∼356 keV) photons. The corresponding correction factors for calibration with Indian phantom are provided. DEs are also simulated for activity distributed as a planar disc at the centre of the axial cavity in each part of the BOMAB phantom (PDAD) and the deviations of these DEs are within 1 % of the ACAD results. Thus, PDAD can also be used for ACAD in scanning geometry. An analytical solution for transmitted mono-energetic photons from a two-dimensional slab is provided for qualitative explanation of difference in DEs due to variation in activity distributions in the phantom. The effect on DEs due to different phantom part dimensions is also studied and lower DEs are observed for larger parts.

Monte Carlo simulation of embedded 241Am activity in injured palm.

This paper describes a methodology to estimate embedded activity of (241)Am and Pu isotopes in a wound at an unknown depth. Theoretical calibration of an array of high-purity germanium detectors is carried out using the Monte Carlo code 'FLUKA' for a (241)Am source embedded at different depths in a soft tissue phantom of dimension 10 × 10 × 4 cm(3) simulating the palm of a worker. It is observed that, in the case of contamination due to pure (241)Am, the ratio of counts in 59.5 and 17.8 keV (Ratio 1) should be used to evaluate the depth, whereas the ratio of counts in 59.5 and 26.3 keV (Ratio 2) should be used when the contamination is due to a mixture of Pu and (241)Am compounds. Variations in the calibration factors (CFs) as well as in the Ratio 1 and Ratio 2 values are insignificant when source dimensions are varied from a point source to a 15-mm diameter circle. It is observed that tissue-equivalent polymethyl methacrylate material can be used in the phantom to estimate the embedded activity, when the activity is located at a depth of <1 cm, as the corresponding CFs do not show much variation with respect to those estimated using the phantom containing soft tissue material. In all other cases, an appropriate soft tissue-equivalent material should be used in the phantom for the estimation of CFs and ratios. The CFs thus obtained will be helpful in an accurate estimation of the depth of the wound and the activity embedded therein in the palm of a radiation worker.

Estimation of specific absorbed fractions for selected organs due to photons emitted by activity deposited in the human respiratory tract using ICRP/ICRU male voxel phantom in FLUKA.

The ICRP/ICRU adult male reference voxel phantom incorporated in Monte Carlo code FLUKA is used for estimating specific absorbed fractions (SAFs) for photons due to the presence of internal radioactive contamination in the human respiratory tract (RT). The compartments of the RT, i.e. extrathoracic (ET1 and ET2) and thoracic (bronchi, bronchioles, alveolar interstitial) regions, lymph nodes of both regions and lungs are considered as the source organs. The nine organs having high tissue weighting factors such as colon, lungs, stomach wall, breast, testis, urinary bladder, oesophagus, liver and thyroid and the compartments of the RT are considered as target organs. Eleven photon energies in the range of 15 keV to 4 MeV are considered for each source organ and the computed SAF values are presented in the form of tables. For the target organs in the proximity of the source organ including the source organ itself, the SAF values are relatively higher and decrease with increase in energy. As the distance between source and target organ increases, SAF values increase with energy and reach maxima depending on the position of the target organ with respect to the source organ. The SAF values are relatively higher for the target organs with smaller masses. Large deviations are seen in computed SAF values from the existing MIRD phantom data for most of the organs. These estimated SAF values play an important role in the estimation of equivalent dose to various target organs of a worker due to intake by inhalation pathway.

Evaluation and assessment of 25 years of environmental radioactivity monitoring data at Tarapur (India) nuclear site.

The evaluation and assessment of monitoring data generated over a period of 1983-2007 (25 years) of a nuclear facility is presented. Time trends of particulate radioactivity, correlation between (137)Cs in discharge canal seawater and station discharged activity and correlation of (137)Cs, (60)Co, and (131)I in marine species such as sponge and Nerita (gastropod) and corresponding discharged activity are discussed. The concentration of (137)Cs and (131)I in seawater versus biota are discussed. A good correlation between (137)Cs in seawater and (137)Cs in liquid waste discharged was observed (R(2) = 0.8, p < 0.001). Similarly, correlation was good for Nerita and discharged concentration of (137)Cs, (131)I and (60)Co (R(2) = 0.55-0.73 and p < 0.001). The measurements over the years indicated that there is no accumulation of radionuclides in either the terrestrial or aquatic environments. The mean (137)Cs decreased from the pre-operational levels: 7.0-3.6 Bq kg(-1) in soil, 0.91-0.016 Bq L(-1) in milk and 0.28-0.036 Bq kg(-1) in vegetation. Similarly, the mean (90)Sr in these matrixes decreased from 3.9 to 0.26 Bq kg(-1); 0.37-0.011 Bq L(-1) and 0.34-0.022 Bq kg(-1) respectively. Cesium-137 of about 700 microBq m(-3) was measured in the air filter disks during 1986 and there was a decrease of three orders of magnitude in concentration over the 25 years. The evaluation of environmental data indicated that the radionuclide concentrations and potential impacts, in terms of effective dose to the members of public, have significantly reduced since 1969.

Comparative assessment of siRNA and shRNA off target effects: what is slowing clinical development.

This review considers comparisons of the off-target effects of siRNA to shRNA and their potential impact on the efficacy and toxicity of RNAi based therapeutics.