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Background: Pediatric molecular imaging requires a balance between administering an activity that will yield sufficient diagnostic image quality while maintaining patient radiation exposure at acceptable levels. In current clinical practice, this balance is arrived at by the current North American Consensus Guidelines in which patient weight is used to recommend the administered activity (AA). Purpose: We have previously demonstrated that girth (waist circumference at the level of the kidneys) is better at equalizing image quality than patient weight for pediatric Tc‐99m DMSA renal function imaging. However, the correlation between image quality (IQ), AA, and patient girth has not been rigorously and systematically developed. In this work, we generate a series of curves showing the tradeoff between AA and IQ as a function of patient girth, providing the data for standards bodies to develop the next generation of dosing guideline for pediatric DMSA SPECT. Methods: An anthropomorphic phantom series that included variations in age (5, 10, and 15 years), gender (M, F), local body morphometry (5, 10, 50, 90, and 95th girth percentiles), and kidney size (±15% standard size), was used to generate realistic SPECT projections. A fixed and clinically challenging defect‐to‐organ volume percentage (0.49% of renal cortex value) was used to model a focal defect with zero uptake (i.e., full local loss of renal function). Task‐based IQ assessment methods were used to rigorously measure IQ in terms of renal perfusion defect detectability. This assessment was performed at multiple count levels (corresponding to various AAs) for groups of patients that had similar girths and defect sizes. Receiver‐operating characteristics (ROC) analysis was applied; the area under the ROC curve (AUC) was used as a figure‐of‐merit for task performance. Curves showing the tradeoff between AUC and AA were generated for these groups of phantoms. Results: Overall, the girth‐based dosing method suggested different amounts of AA compared to weight‐based dosing for the phantoms that had a relatively large body weight but a small girth or phantoms with relatively small bodyweight but large girth. Reductions of AA to 62.9% compared to weight‐based dosing guidelines can potentially be realized while maintaining a baseline (AUC = 0.80) IQ for certain 15‐year‐olds who have a relatively small girth and large defect size. Note that the task‐based IQ results are heavily dependent on the simulated defect size for the defect detection task and the appropriate AUC value must be decided by the physicians for this diagnostic task. These results are based purely on simulation and are subject to future clinical validation. Conclusions: The study provides simulation‐based IQ‐AA data for a girth‐based dosing method for pediatric renal SPECT, suggesting that patient waist circumference at the level of kidneys should be considered in selecting the AA needed to achieve an acceptable IQ. This data may be useful for standards bodies to develop girth‐based dosing guidelines. [ABSTRACT FROM AUTHOR]

Background: Potential risk associated with low‐dose radiation exposures is often expressed using the effective dose (E) quantity. Other risk‐related quantities have been proposed as alternatives. The recently introduced risk index (RI) shares similarities with E but expands the metric to incorporate medical imaging‐appropriate risks factors including patient‐specific size, age, and sex. Purpose: The aim of this work is to examine the RI metric for quantifying stochastic radiation risk and demonstrate its applications in nuclear imaging. The advantages in this improved metric may help the field progress toward stratified risk consideration in the course of patient management, improve efforts for procedure optimization, and support an evolution in the science of radiation risk assessment. Methods: In this study we describe, implement, and calculate RI for various diagnostic nuclear imaging scenarios using reference biokinetics published in ICRP Publication 128 for commonly utilized radiopharmaceuticals. All absorbed dose, E and RI calculations were performed using the freely available MIRDcalc nuclear medicine dosimetry software; the organ specific risk parameters used in the software are also benchmarked in this text. The resulting RI and E values are compared and various trends in RI values identified. Results: E and RI coefficients were calculated for 3016 use cases. Notably RI values vary depending on patient characteristics. Overall, across the population, global trends in RI values can be identified. In general, RI values were 2.15 times higher for females than males, due to higher risk coefficients and activities being distributed in smaller reference masses. The pediatric patients showed higher RIs than adults, as younger patients generally receive higher absorbed doses per administered activity, and are more radiosensitive, and have a longer projected lifespan at risk. A compendium of E and RI values is also provided in table format to serve as a reference for the community. Conclusions: RI is a rational quantity that could be used for justification, risk communication and protocol optimization in medical imaging. It has some advantages when compared to the long‐utilized E value with respect to personalization, since accounts for patient size, age, sex, and natural incidence of cancer risk. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) elongate in the direction of blood flow, are stiffer, and are considered atheroprotective in areas of the vasculature where flow‐induced shear stress is high and unidirectional and are softer, atherogenic, and polygonal in areas experiencing oscillatory multidirectional flow. To understand the precise roles of EC mechanics and morphology in the uptake of therapeutic nanoparticles (NPs) by atherogenic endothelium, human aortic ECs are induced to adopt prescribed shapes and areas imposed by microcontact patterned adhesive islands. NP uptake per cell increases with increasing spreading area and decreases with increasing cell aspect ratio at constant cell spreading area. Biomechanical analysis shows that elongated cells exhibit higher cellular stress and stiffer membranes than cells with low aspect ratios, indicating a strong correlation between morphology, mechanical phenotype, and NP uptake. Further, ECs elongated by high laminar shear endocytosed NPs to a far lesser extent than those that are nonelongated in the chaotic, lower shear areas when cocultured in the same chamber. Results indicate that conditions leading to atherogenesis, such as low, chaotic shear‐induction of EC polygonal morphology may be used to increase the uptake of therapeutic NPs as a preventative measure against atherosclerosis. [ABSTRACT FROM AUTHOR]

Keywords: archeology; baselines; cities; community science; museums; paleontology; urban ecology; paleoecology EN archeology baselines cities community science museums paleontology urban ecology paleoecology 1 5 5 12/01/22 20221201 NES 221201 A fundamental challenge for 21st century conservation is to develop goals that are meaningful and attainable in a world shaped by anthropogenic change (Kareiva & Marvier, [10]). These separate data sources can be used to understand the deep-time natural history, recent human history, or current ecology of urban landscapes in isolated conservation contexts. This narrow view downplays conservation efforts in urban areas and limits the ability of cities to support biodiversity; decreases access to ecosystem services for many people; and facilitates actions that result in environmental injustices. Archeology, baselines, cities, museums, paleontology, urban ecology, paleoecology, community science. [Extracted from the article]

Improving targeting efficacy has been a central focus of the studies on nanoparticle (NP)-based drug delivery nanocarriers over the past decades. As cells actively sense and respond to the local physical environments, not only the NP design (e.g., size, shape, ligand density, etc.) but also the cell mechanics (e.g., stiffness, spreading, expressed receptors, etc.) affect the cellular uptake efficiency. While much work has been done to elucidate the roles of NP design for cells seeded on a flat tissue culture surface, how the local physical environments of cells mediate uptake of NPs remains unexplored, despite the widely known effect of local physical environments on cellular responses in vitro and disease states in vivo. Here, we report the active responses of human osteosarcoma cells to fibrous substrate topographies and the subsequent changes in the cellular uptake of NPs. Our experiments demonstrate that surface topography modulates cellular uptake efficacy by mediating cell spreading and membrane mechanics. The findings provide a concrete example of the regulative role of the physical environments of cells on cellular uptake of NPs, therefore advancing the rational design of NPs for enhanced drug delivery in targeted cancer therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 488-495, 2016. [ABSTRACT FROM AUTHOR]

Polymeric nanoparticles ( NPs) are one of the most studied organic strategies for nanomedicine. Intense interest lies in the potential of polymeric NPs to revolutionize modern medicine. To determine the ideal nanosystem for more effective and distinctly targeted delivery of therapeutic applications, particle size, morphology, material choice, and processing techniques are all research areas of interest. Utilizations of polymeric NPs include drug delivery techniques such as conjugation and entrapment of drugs, prodrugs, stimuli-responsive systems, imaging modalities, and theranostics. Cancer, neurodegenerative disorders, and cardiovascular diseases are fields impacted by NP technologies that push scientific boundaries to the leading edge of transformative advances for nanomedicine. WIREs Nanomed Nanobiotechnol 2016, 8:271-299. doi: 10.1002/wnan.1364 For further resources related to this article, please visit the [ABSTRACT FROM AUTHOR]

Natural bone apatite crystals, which mediate the development and regulate the load-bearing function of bone, have recently been associated with strongly bound citrate molecules. However, such understanding has not been translated into bone biomaterial design and osteoblast cell culture. In this work, we have developed a new class of biodegradable, mechanically strong, and biocompatible citrate-based polymer blends (CBPBs), which offer enhanced hydroxyapatite binding to produce more biomimetic composites (CBPBHAs) for orthopedic applications. CBPBHAs consist of the newly developed osteoconductive citrate-presenting biodegradable polymers, crosslinked urethane-doped polyester and poly (octanediol citrate), which can be composited with up to 65 wt % hydroxyapatite. CBPBHA networks produced materials with a compressive strength of 116.23 ± 5.37 MPa comparable to human cortical bone (100-230 MPa), and increased C2C12 osterix gene and alkaline phosphatase gene expression in vitro. The promising results above prompted an investigation on the role of citrate supplementation in culture medium for osteoblast culture, which showed that exogenous citrate supplemented into media accelerated the in vitro phenotype progression of MG-63 osteoblasts. After 6 weeks of implantation in a rabbit lateral femoral condyle defect model, CBPBHA composites elicited minimal fibrous tissue encapsulation and were well integrated with the surrounding bone tissues. The development of citrate-presenting CBPBHA biomaterials and preliminary studies revealing the effects of free exogenous citrate on osteoblast culture shows the potential of citrate biomaterials to bridge the gap in orthopedic biomaterial design and osteoblast cell culture in that the role of citrate molecules has previously been overlooked. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2521-2532, 2014. [ABSTRACT FROM AUTHOR]

The major challenge for bone tissue engineering lies in the fabrication of scaffolds that can mimic the extracellular matrix and promote osteogenesis. Electrospun fibers are being widely researched for this application due to high porosity, interconnectivity, and mechanical strength of the fibrous scaffolds. Electrospun poly methyl methacrylate (PMMA, 2.416 ± 0.100 μm) fibers were fabricated and etched using a 60% propylene glycol methyl ether acetate (PGMEA)/limonene (vol/vol) solution to obtain fiber diameters ranging from 2.5 to 0.5 μm in a time-dependent manner. The morphology of the fibrous scaffolds was evaluated using scanning electron microscopy and cellular compatibility with etchant-treated scaffold was assessed using immunoflurescence. Mitogen-activated protein kinases (MAPK) activation in response to different fiber diameter was evaluated with western blot as well as quantitative in-cell western. We report that electrospun micro-fibers can be etched to 0.552 ± 0.047 μm diameter without producing beads. Osteoblasts adhered to the fibers and a change in fiber diameter played a major role in modulating the activation of extracellular signal-regulated kinase (ERK) and p38 kinases with 0.882 ± 0.091 μm diameter fibers producing an inverse effect on ERK and p38 phosphorylation. These results indicate that nanofibers produced by wet etching can be effectively utilized to produce diameters that can differentially modulate MAPK activation patterns. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:2921-2928, 2012. [ABSTRACT FROM AUTHOR]

The long‐term goal of this work is to develop biomimetic polymer‐based systems for bone regeneration that both allow for neutral pH degradation products and have the ability to nucleate bonelike apatite. In this study, the etheric biodegradable polyphosphazene, poly[(50%ethyl glycinato)(50%methoxyethoxyethoxy)phosphazene] (PNEG50MEEP50) was blended with poly(lactide‐co‐glycolide) PLAGA and studied their ability to produce high‐strength degradable biomaterials with bioactivity. Accordingly, two blends with weight ratios of PNEG50MEEP50 to PLAGA 25:75 (BLEND25) and 50:50 (BLEND50) were fabricated using a mutual solvent approach. Increases in PNEG50MEEP50 content in the blend system resulted in decreased elastic modulus of 779 MPa when compared with 1684 MPa (PLAGA) as well as tensile strength 7.9 MPa when compared with 25.7 MPa (PLAGA). However, the higher PNEG50MEEP50 content in the blend system resulted in higher Ca/P atomic ratio of the apatite layer 1.35 (BLEND50) when compared with 0.69 (BLEND25) indicating improved biomimicry. Furthermore, these blends supported primary rat osteoblast adhesion and proliferation with an enhanced phenotypic expression when compared with PLAGA. These findings establish the suitability of PNEG50MEEP50‐PLAGA biodegradable blends as promising bioactive materials for orthopedic applications. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010 [ABSTRACT FROM AUTHOR]

The cover image, by Brittany Baniket al., is based on the Advanced Review Polymeric Nanoparticles: The Future of Nanomedicine, DOI: . [ABSTRACT FROM AUTHOR]

Solvent/non‐solvent sintering creates porous polymeric microsphere scaffolds suitable for tissue engineering purposes with control over the resulting porosity, average pore diameter, and mechanical properties. Five different biodegradable biocompatible polyphosphazenes exhibiting glass transition temperatures from −8 to 41°C and poly (lactide‐co‐glycolide), (PLAGA) a degradable polymer used in a number of biomedical settings, were examined to study the versatility of the process and benchmark the process to heat sintering. Parameters such as: solvent/non‐solvent sintering solution composition and submersion time effect the sintering process. PLAGA microsphere scaffolds fabricated with solvent/non‐solvent sintering exhibited an interconnected porosity and pore size of 31.9% and 179.1 μm, respectively which was analogous to that of conventional heat sintered PLAGA microsphere scaffolds. Biodegradable polyphosphazene microsphere scaffolds exhibited a maximum interconnected porosity of 37.6% and a maximum compressive modulus of 94.3 MPa. Solvent/non‐solvent sintering is an effective strategy for sintering polymeric microspheres, with a broad spectrum of glass transition temperatures, under ambient conditions making it an excellent fabrication route for developing tissue engineering scaffolds and drug delivery vehicles. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008 [ABSTRACT FROM AUTHOR]