No abstract

It is not feasible to define very small or complex organs and tissues in the current voxel-type adult reference computational phantoms of the International Commission on Radiological Protection (ICRP), which limit dose coefficients for weakly penetrating radiations. To address the problem, the ICRP is converting the voxel-type reference phantoms into mesh-type phantoms. In the present study, as a part of the conversion project, the micrometer-thick target and source regions in the alimentary and respiratory tract systems as described in ICRP Publications 100 and 66 were included in the mesh-type ICRP reference adult male and female phantoms. In addition, realistic lung airway models were simulated to represent the bronchial (BB) and bronchiolar (bb) regions. The electron specific absorbed fraction (SAF) values for the alimentary and respiratory tract systems were then calculated and compared with the values calculated with the stylized models of ICRP Publications 100 and 66. The comparisons show generally good agreement for the oral cavity, oesophagus, and BB, whereas for the stomach, small intestine, large intestine, extrathoracic region, and bb, there are some differences (e.g. up to ~9 times in the large intestine). The difference is mainly due to anatomical difference in these organs between the realistic mesh-type phantoms and the simplified stylized models. The new alimentary and respiratory tract models in the mesh-type ICRP reference phantoms preserve the topology and dimensions of the voxel-type ICRP phantoms and provide more reliable SAF values than the simplified models adopted in previous ICRP Publications.

Committee 2 of the International Commission on Radiological Protection (ICRP) has constructed mesh-type adult reference computational phantoms by converting the voxel-type ICRP Publication 110 adult reference computational phantoms to a high-quality mesh format, and adding those tissues that were below the image resolution of the voxel phantoms and therefore not included in the Publication 110 phantoms. The new mesh phantoms include all the necessary source and target tissues for effective dose calculations, including the 8-40-µm-thick target layers of the alimentary and respiratory tract organs, thereby obviating the need for supplemental organ-specific stylised models (e.g. respiratory airways, alimentary tract organ walls and stem cell layers, lens of the eye, and skin basal layer). To see the impact of the new mesh-type reference phantoms, dose coefficients for some selected external and internal exposures were calculated and compared with the current reference values in ICRP Publications 116 and 133, which were calculated by employing the Publication 110 phantoms and the supplemental stylised models. The new mesh phantoms were also used to calculate dose coefficients for industrial radiography sources near the body, which can be used to estimate the organ doses of the worker who is accidentally exposed by an industrial radiography source; in these calculations, the mesh phantoms were deformed to reflect the size of the worker, and also to evaluate the effect of posture on dose coefficients.

Adipose tissue macrophage (ATM)-mediated inflammation is a key feature contributing to the adverse metabolic outcomes of dietary obesity. Recruitment of macrophages to obese adipose tissues (AT) can occur through the engagement of CCR2, the receptor for MCP-1 (monocyte chemoattractant protein-1), which is expressed on peripheral monocytes/macrophages. Here, we show that i.p. administration of a rabies virus glycoprotein-derived acetylcholine receptor-binding peptide effectively delivers complexed siRNA into peritoneal macrophages and ATMs in a mouse model of high-fat diet-induced obesity. Treatment with siRNA against CCR2 inhibited macrophage infiltration and accumulation in AT and, therefore, proinflammatory cytokines produced by macrophages. Consequently, the treatment significantly improved glucose tolerance and insulin sensitivity profiles, and also alleviated the associated symptoms of hepatic steatosis and reduced hepatic triglyceride production. These results demonstrate that disruption of macrophage chemotaxis to the AT through cell-targeted gene knockdown strategies can provide a therapeutic intervention for obesity-related metabolic diseases. The study also highlights a siRNA delivery approach for targeting specific monocyte subsets that contribute to obesity-associated inflammation without affecting the function of other tissue-resident macrophages that are essential for host homeostasis and survival.

Mesh-type and voxel-based computational phantoms comprise the current state of the art for internal dose assessment via Monte Carlo simulations but excel in different aspects, with mesh-type phantoms offering advantages over their voxel counterparts in terms of their flexibility and realistic representation of detailed patient-or subjectspecific anatomy. We have developed PARaDIM (pronounced "paradigm": Particle and Heavy Ion Transport Code System-Based Application for Radionuclide Dosimetry in Meshes), a freeware application for implementing tetrahedral mesh-type phantoms in absorbed dose calculations. It considers all medically relevant radionuclides, including α, β, γ, positron, and Auger/conversion electron emitters, and handles calculation of mean dose to individual regions, as well as 3-dimensional dose distributions for visualization and analysis in a variety of medical imaging software. This work describes the development of PARaDIM, documents the measures taken to test and validate its performance, and presents examples of its uses. Methods: Human, small-animal, and cell-level dose calculations were performed with PARaDIM and the results compared with those of widely accepted dosimetry programs and literature data. Several tetrahedral phantoms were developed or adapted using computer-aided modeling techniques for these comparisons. Results: For human dose calculations, agreement of PARaDIM with OLINDA 2.0 was good-within 10%-20% for most organs-despite geometric differences among the phantoms tested. Agreement with MIRDcell for cell-level S value calculations was within 5% in most cases. Conclusion: PARaDIM extends the use of Monte Carlo dose calculations to the broader community in nuclear medicine by providing a user-friendly graphical user interface for calculation setup and execution. PARaDIM leverages the enhanced anatomic realism provided by advanced computational reference phantoms or bespoke image-derived phantoms to enable improved assessments of radiation doses in a variety of radiopharmaceutical use cases, research, and preclinical development. PARaDIM can be downloaded freely at www.paradim-dose.org.

This study clarifies the previously unknown limitations of the entropy-based land-use mix index and suggests conditions under which the index is valid. The land-use mix index has an n-shaped relationship to dependent variables, which was evidenced by this study, but previous studies have ignored the problem. This study identified a non-linear relationship between the land-use mix index and a common dependent variable of interest, pedestrian volume. Pedestrian volume is a common measure of the vitality of a district and/or a city and a major goal of urban design and regeneration. Using mathematical analysis, simulation, and empirical analysis, this study found that the land-use mix index had an inconsistent quadratic relationship to pedestrian volume. It was confirmed that an analytical model using the land-use mix index, and that index squared, should be used together when samples representative of entire cities are tested. Otherwise, in samples from predominantly residential areas, the land-use mix index positively relates to pedestrian volume, whereas, in predominantly commercial areas, it will be negative. Previous studies failed to observe the hidden side of the entropy-based land-use mix index in commercial areas because their focus was mainly on residential areas or residents. Future studies should clarify the logical and theoretical relationships between the index and the outcome variable of interest, review the characteristics of the data and, then, implement appropriate statistical analyses by being aware of the hidden side.

No abstract

Following the issuance of new radiological protection recommendations in ICRP Publication 103, the Commission released, in ICRP Publication 110, the adult male and female voxel-type reference computational phantoms to be used for calculation of the reference dose coefficients (DCs) for both external and internal exposures. While providing more anatomically realistic representations of internal anatomy than the older stylised phantoms, the voxel phantoms have their limitations, mainly due to voxel resolution, especially with respect to small tissue structures (e.g. lens of the eye) and very thin tissue layers (e.g. stem cell layers in the stomach wall mucosa and intestinal epithelium). This publication describes the construction of the adult mesh-type reference computational phantoms (MRCPs) that are the modelling counterparts of the Publication 110 voxel-type reference computational phantoms. The MRCPs include all source and target regions needed for estimating effective dose, even the micrometre-thick target regions in the respiratory and alimentary tract organs, skin, and urinary bladder, assimilating the supplementary stylised models. The MRCPs can be implemented directly into Monte Carlo particle transport codes for dose calculations (i.e. without voxelisation), fully maintaining the advantages of the mesh geometry. DCs of organ dose and effective dose and specific absorbed fractions (SAFs) calculated with the MRCPs for some external and internal exposures show that À while some differences were observed for small tissue structures and for weakly-penetrating radiations À the MRCPs provide the same or very similar values as the previously published reference DCs and SAFs, which were calculated with the Publication 110 reference phantoms and supplementary stylised models, for most tissues and penetrating radiations. Consequently, the DCs for effective dose (i.e. the fundamental protection quantity) were not found to be different. The DCs of ICRP Publication 116 and the SAFs of ICRP Publication 133 thus remain valid.