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Cities with high levels of bicycling tend to be some of the safest cities for all road users. This paper investigates why this relationship exists for fourteen small and mid-sized cities across the U.S. (seven with high bicycling rates and seven paired comparison cities) using ten years of data and hierarchical negative binomial regression models. Findings confirm that higher-bicycling cities are significantly associated with better overall road safety outcomes. In terms of mode choice differences, pedestrian ‘safety in numbers’ as well as reduced driving activity had a positive impact on pedestrian safety. Results from hierarchical negative binomial regressions also suggest that more compact cities were significantly associated with better road safety outcomes for all road users. In terms of socio-demographic and socio-economic factors, the results reveal equity concerns with areas with lower incomes and more non-White residents seeing more overall road fatalities.

Abstract Purpose To develop a model of the internal vasculature of the adult liver and demonstrate its application to the differentiation of radiopharmaceutical decay sites within liver parenchyma from those within organ blood. Method Computer-generated models of hepatic arterial (HA), hepatic venous (HV), and hepatic portal venous (HPV) vascular trees were algorithmically created within individual lobes of the ICRP adult female and male livers (AFL/AML). For each iteration of the algorithm, pressure, blood flow, and vessel radii within each tree were updated as each new vessel was created and connected to a viable bifurcation site. The vascular networks created inside the AFL/AML were then tetrahedralized for coupling to the PHITS radiation transport code. Specific absorbed fractions (SAF) were computed for monoenergetic alpha particles, electrons, positrons, and photons. Dual-region liver models of the AFL/AML were proposed, and particle-specific SAF values were computed assuming radionuclide decays in blood within two locations: (1) sites within explicitly modeled hepatic vessels, and (2) sites within the hepatic blood pool residing outside these vessels to include the capillaries and blood sinuses. S values for 22 and 10 radionuclides commonly used in radiopharmaceutical therapy and imaging, respectively, were computed using the dual-region liver models and compared to those obtained in the existing single-region liver model. Results Liver models with virtual vasculatures of ~ 6000 non-intersecting straight cylinders representing the HA, HPV, and HV circulations were created for the ICRP reference. For alpha emitters and for beta and auger-electron emitters, S values using the single-region models were approximately 11% (AML) to 14% (AFL) and 11% (AML) to 13% (AFL) higher than the S values obtained using the dual-region models, respectively. Conclusions The methodology employed in this study has shown improvements in organ parenchymal dosimetry through explicit consideration of blood self-dose for alpha particles (all energies) and for electrons at energies below ~ 100 keV.

Abstract 99mTc-DMSA is one of the most commonly used pediatric nuclear medicine imaging agents. Nevertheless, there are no pharmacokinetic (PK) models for 99mTc-DMSA in children, and currently available pediatric dose estimates for 99mTc-DMSA use pediatric S values with PK data derived from adults. Furthermore, the adult PK data were collected in the mid-70’s using quantification techniques and instrumentation available at the time. Using pediatric imaging data for DMSA, we have obtained kinetic parameters for DMSA that differ from those applicable to adults. Methods We obtained patient data from a retrospective re-evaluation of clinically collected pediatric SPECT images of 99mTc-DMSA in 54 pediatric patients from Boston’s Children Hospital (BCH), ranging in age from 1 to 16 years old. These were supplemented by prospective data from twenty-three pediatric patients (age range: 4 months to 6 years old). Results In pediatric patients, the plateau phase in fractional kidney uptake occurs at a fractional uptake value closer to 0.3 than the value of 0.5 reported by the International Commission on Radiological Protection (ICRP) for adult patients. This leads to a 27% lower time-integrated activity coefficient in pediatric patients than in adults. Over the age range examined, no age dependency in uptake fraction at the clinical imaging time was observed. Female pediatric patients had a 17% higher fractional kidney uptake at the clinical imaging time than males (P < 0.001). Conclusions Pediatric 99mTc-DMSA kinetics differ from those reported for adults and should be considered in pediatric patient dosimetry. Alternatively, the differences obtained in this study could reflect improved quantification methods and the need to re-examine DMSA kinetics in adults.

Abstract Background Dosimetry for diagnostic agents is performed to assess the risk of radiation detriment (e.g., cancer) associated with the imaging agent and the risk is assessed by computing the effective dose coefficient, e. Stylized phantoms created by the MIRD Committee and updated by work performed by Cristy-Eckerman (CE) have been the standard in diagnostic dosimetry. Recently, the ICRP developed voxelized phantoms, which are described in ICRP Publication 110. These voxelized phantoms are more realistic and detailed in describing human anatomy compared with the CE stylized phantoms. Ideally, all tissues should be represented and their pharmacokinetics collected for an as accurate a dosimetric calculation as possible. As the number of source tissues included increases, the calculated e becomes more accurate. There is, however, a trade-off between the number of source tissues considered, and the time and effort required to measure the time-activity curve for each tissue needed for the calculations. In this study, we used a previously published 68Ga-DOTA-TATE data set to examine how the number of source tissues included for both the ICRP voxelized and CE stylized phantoms affected e. Results Depending upon the number of source tissues included e varied between 14.0–23.5 μSv/MBq for the ICRP voxelized and 12.4–27.7 μSv/MBq for the CE stylized phantoms. Furthermore, stability in e, defined as a < 10% difference between e obtained using all source tissues compared to one using fewer source tissues, was obtained after including 5 (36%) of the 14 source tissues for the ICRP voxelized, and after including 3 (25%) of the 12 source tissues for the CE stylized phantoms. In addition, a 2-fold increase in e was obtained when all source tissues where included in the calculation compared to when the TIAC distribution was lumped into a single reminder-of-body source term. Conclusions This study shows the importance of including the larger tissues like the muscles and remainder-of-body in the dosimetric calculations. The range of e based on the included tissues were less for the ICRP voxelized phantoms using tissue weighting factors from ICRP Publication 103 compared to CE stylized phantoms using tissue weighting factors from ICRP Publication 60.

This article examines blackfishing, a practice in which cultural and economic agents appropriate Black culture and urban aesthetics in an effort to capitalize on Black markets. Specifically, this study analyzes the Instagram accounts of four influencers (Instagram models) who were accused of blackfishing in late 2018 and is supplemented with a critical analysis of 27 news and popular press articles which comprise the media discourse surrounding the controversy. Situated within the literature on cultural appropriation and urban redevelopment policies, this study explores how Black identity is mined for its cultural and economic value in the context of digital labor. I assert that Instagram’s unique platform affordances (including its racial affordances) and the neoliberal logics which undergird cultural notions of labor facilitate the mechanisms by which Black identity is rendered a lucrative commodity vis-à-vis influencing.

To advance healthy transportation via increased bicycling, cities combat one of the primary barriers to such cycling – traffic safety concerns – through the provision of various bicycle treatments. Shared lane markings (more commonly known as “sharrows”) are an increasingly common treatment utilized to improve bicyclist safety. While past research confirms that sharrows may effectively influence spacing and other operational measures, the impact on actual safety outcomes remains unsubstantiated due to a lack of dooring-related bicycle crash data. Fortunately, the city of Chicago instituted a program to collect dooring crash data in 2010. Thus, the purpose of this research is to longitudinally examine the association between sharrows and bicyclist injuries by combining traditional crash data with dooring-related crash data.To perform this examination, we divide Census block groups in Chicago into three categories based on what bicycle treatment was installed between the years 2011 and 2014: (i) those block groups with no bicycle facilities installed; (ii) those with only sharrows installed; or (iii) those with only bicycle lanes (standard, buffered, and/or protected) installed. Negative binomial regressions and Kruskal–Wallis tests suggest that block groups with only sharrows installed experienced the largest increase in bicyclist injury rates, with exposure being accounted for through levels of bicycle commuter activity. This relationship held true for overall crashes as well as for dooring-related crashes. These findings raise concerns regarding the safety effectiveness of sharrows as used by the City of Chicago during the study period and should be a call for more research on the subject in a variety of different contexts using various exposure metrics. Keywords: Shared lane markings, Sharrows, Bicycle lane, Safety, Dooring crashes

Interactions between climate and hydrogeologic settings contribute to the hydrologic and chemical variability among depressional wetlands, which influences their aquatic communities. These interactions and resulting variability have led to inconsistent results in terms of identifying reliable predictors of aquatic-macroinvertebrate community composition for depressional wetlands. This is especially true in the Prairie Pothole Region of North America where, in addition to pronounced climate variability, studies are often confounded by fish introductions. We used environmental monitoring data collected over a 24-year period from a complex of sixteen depressional wetlands and structural equation modeling techniques that incorporated theoretical and empirical relationships outlined in the Wetland Continuum to identify key environmental (climate and hydrogeologic setting) and biotic (competition and predation) drivers of aquatic-macroinvertebrate community composition for prairie-pothole wetlands. Uplands in the study area were primarily native prairie, thus, embedded wetlands were impacted minimally by agricultural influences. Additionally, study wetlands were predominately fishless. In the absence of the overwhelming influence of fishes, major drivers influencing aquatic-macroinvertebrate communities were revealed through the use of data spanning multidecadal-long climate cycles. We found variables related to the placement of wetlands along axes of the Wetland Continuum, e.g., hydrogeologic setting (relative wetland elevation) and hydroclimatic setting (proportion of wetland ponded), to be influential drivers of within-wetland habitat characteristics, such as the proportion of open-water area, which in turn was the strongest predictor of macroinvertebrate community composition. In contrast, predatory invertebrate and salamander abundance and non-predatory invertebrate biomass (i.e., predation and competition) were found to have minimal influence on community composition.

The National Highway Traffic Safety Administration cites decreasing bicyclist fatalities in the United States over the past several decades as evidence of improved bicycling safety. However, with users possessing a diverse range of tolerances, purposes, and socio-demographics, bicycle safety is an important yet complex problem, one that does not have a simple yes/no answer. To gain a better understanding, we need to take a variety of perspectives. Traditional bicycle safety analyses take a transportation engineering perspective by using distance-based exposure metrics or those based on the number of trips. But there are other perspectives – such as public health (using population) and transportation planning (using bicycle participation) – that could provide us with a fuller picture. This paper applies four measures of bicycling exposure to take a broad, interdisciplinary perspective on bicycling safety to answer the question of whether bicycling is actually getting safer and, if so, for whom. We first explore age differences with respect to the direction and magnitude of bicyclist fatality rates in the United States between 1985 and 2017. We then investigate whether any safety benefits are shared equally among commuters and recreational riders.Using fatality data from the Fatality Analysis Reporting System (FARS) and exposure data from the National Household Travel Survey (NHTS), the American Community Survey (ACS), the U.S. Census, and the National Sporting Goods Association (NSGA) – a relatively novel approach to measuring exposure through a comprehensive national bicycling participation survey – we derived trends of age-specific bicyclist fatality rates and corresponding confidence intervals for children and adults. We also compare exposure to fatality outcomes by deriving Pearson's correlation coefficients. This is the first research to provide a longitudinal, age-specific statistical analysis of bicycle fatality rates using these four exposure metrics.Results suggest that overall declines in bicycle fatality rates have been primarily driven by a sharp decline in child bicyclist fatalities while adult bicycle fatality rates have generally trended upwards (especially for the general population) or remained stagnant (for commuters). This work adds to the understanding of bicyclist safety and gives direction to future research regarding the importance of considering age and exposure sources.

Flood damages occur when just one inch of water enters a residential household and models of flood damage estimation are sensitive to first-floor elevation (FFE). The current sources for FFEs consist of costly survey-based elevation certificates (ECs) or assumptions based on year built, foundation type, and flood zone. We sought to address these limitations by establishing the role of an Unmanned Aerial System (UAS) to efficiently derive accurate FFEs. Four residential communities within Galveston Island, Texas were selected to assess efficient flight parameters required for UAS photogrammetry within the built environment. A real-time kinematic positioning enabled (RTK) UAS was then used to gather georeferenced aerial imagery and create detailed 3D photogrammetric models with ±0.02 m horizontal and ±0.05 m vertical accuracies. From these residential models, FFEs and other structural measurements present in traditional ECs were obtained. Comparative statistical analyses were performed using the UAS-based measurements and traditional EC measurements. UAS based FFE measurements achieved 0.16 m mean absolute error (MAE) across all comparative observations and were not statistically different from traditional EC measures. We conclude the RTK enabled UAS approach is an efficient, cost-effective method in establishing accurate FFEs and other flood-sensitive measures in residential communities.

Abstract Background Computed Tomography (CT) contributes up to 50% of the medical exposure to the United States population. Children are considered to be at higher risk of developing radiation-induced tumors due to the young age of exposure and increased tissue radiosensitivity. Organ dose estimation is essential for pediatric and adult patient cancer risk assessment. The objective of this study is to validate the VirtualDose software in comparison to currently available software and methods for pediatric and adult CT organ dose estimation. Methods Five age groups of pediatric patients and adult patients were simulated by three organ dose estimators. Head, chest, abdomen-pelvis, and chest-abdomen-pelvis CT scans were simulated, and doses to organs both inside and outside the scan range were compared. For adults, VirtualDose was compared against ImPACT and CT-Expo. For pediatric patients, VirtualDose was compared to CT-Expo and compared to size-based methods from literature. Pediatric to adult effective dose ratios were also calculated with VirtualDose, and were compared with the ranges of effective dose ratios provided in ImPACT. Results In-field organs see less than 60% difference in dose between dose estimators. For organs outside scan range or distributed organs, a five times’ difference can occur. VirtualDose agrees with the size-based methods within 20% difference for the organs investigated. Between VirtualDose and ImPACT, the pediatric to adult ratios for effective dose are compared, and less than 21% difference is observed for chest scan while more than 40% difference is observed for head-neck scan and abdomen-pelvis scan. For pediatric patients, 2 cm scan range change can lead to a five times dose difference in partially scanned organs. Conclusions VirtualDose is validated against CT-Expo and ImPACT with relatively small discrepancies in dose for organs inside scan range, while large discrepancies in dose are observed for organs outside scan range. Patient-specific organ dose estimation is possible using the size-based methods, and VirtualDose agrees with size-based method for the organs investigated. Careful range selection for CT protocols is necessary for organ dose optimization for pediatric and adult patients.

The USP heparin sodium monograph lists impurities with specifications developed for porcine derived products. Most of these impurities are of biological origin and are present in porcine intestinal mucosa, the tissue source used in the production of porcine heparin. One of the specified impurities, oversulfated chondroitin sulfate (OSCS), has been introduced in the monograph to detect intended adulteration of heparin products with this impurity. The evaluation of bovine intestinal heparin as an alternative source of pharmaceutical heparin included an evaluation of bovine heparin with the current USP heparin sodium monograph methods. This evaluation included a comparison of impurity quantities observed in multiple bovine intestinal heparin samples against the specifications found in the USP heparin sodium monograph. The impurities investigated in this study were protein, galactosamine, nucleotidic impurities, and OSCS. Bovine intestinal heparin met the requirements in the tests for protein, galactosamine, and nucleotidic impurities. A potential issue was observed with the strong anion exchange high performance liquid chromatography (SAX-HPLC) used to analyze for the presence of OSCS. While the OSCS was well-resolved from the bovine heparin peak, the resolution of dermatan sulfate from heparin did not consistently meet system suitability requirements in the current USP Heparin sodium monograph. The overall levels of impurities observed in bovine intestinal mucosal heparin were comparable to those observed in porcine intestinal mucosal heparin. Bovine intestinal mucosal heparin can be produced with acceptable impurity levels that align with these important quality attributes found in porcine heparin.

Objective: To understand the different methodologies used to elicit willingness to pay for health and the value of a statistical life year through surveys. Methodology: A systematic review of the literature was undertaken to identify studies using surveys to estimate either willingness to pay for health or the value of a statistical life year. Each study was reviewed and the study setting, sample size, sample description, survey administration (online or face to face), survey methodology, and results were extracted. The results of the studies were then compared to any published national guidelines of cost-effectiveness thresholds to determine their accuracy. Results: Eighteen studies were included in the review with 15 classified as willingness to pay and 3 value of a statistical life. The included studies covered Asia (n = 6), Europe (n = 4), the Middle East (n = 1), and North America (n = 5), with one study taking a global perspective. There were substantial differences in both the methodologies and the estimates of both willingness to pay and value of a statistical life between the different studies. Conclusion: Different methods used to elicit willingness to pay and the value of a statistical life year resulted in a wide range of estimates.

Investigating emerging transportation services is critical to forecasting mode choice and providing appropriate infrastructure. One such infrastructure is parking, as parking demand may shift with the availability of ride-hailing services. This study uses ethnographic methods—complemented with passenger surveys collected when driving for Uber and Lyft in the Denver, Colorado, region—to gather quantitative and qualitative data on ride-hailing and analyze the impacts of ride-hailing on parking, including changes in parking demand and parking as a reason to deter driving. The study also examines relationships between parking time and cost. This includes building a classification tree-based model to predict the replaced driving trips as a function of car ownership, destination land type, parking stress, and demographics. The results suggest that: i) ride-hailing is replacing driving trips and could reduce parking demand, particularly at land uses such as airports, event venues, restaurants, and bars; ii) parking stress is a key reason respondents chose not to drive; and iii) respondents are generally willing to pay more for reduced parking time and distance. Conversely, parking supply, time, and cost can all influence travel behavior and ride-hailing use. This study provides insight into potential benefits and disadvantages of ride-hailing as related to parking.

Meckel's diverticula are common congenital gastrointestinal malformations that most often present with bloody stool or bowel obstruction. Occasionally these diverticula may become inverted and serve as a lead point for the development of intussusception. Herein, we report the case of a 10-year old female presenting with abdominal pain and non-bloody, non-bilious emesis and suspicion of intussusception. Upon performing an exploratory laparotomy, the intussusception lead point was found to be an inverted Meckel's diverticulum obstructing the lumen of the intestine.

Perianal abscess and fistula-in-ano are well-described in the pediatric population. They are most common in infants less than 1 year of age and often resolve with oral antibiotics; occasionally they require drainage or fistulotomy. The etiology is commonly associated with cryptoglandular obstruction and subsequent infection, however alternative diagnoses should be considered in cases of recurrent abscesses and fistulae that are refractory to standard treatments. In this report, we present the case of an 8-year-old boy with a complex, recurrent fistula-in-ano that resulted from a rare congenital perirectal dermoid cyst.

This study aimed to verify the influence of partial dehydration of "Niagara Rosada" grape clusters in physicochemical quality of the pre- fermentation must. In Brazil, during the winemaking process it is common to need to adjust the grape must when the physicochemical characteristics of the raw material are insufficient to produce wines in accordance with the Brazilian legislation for classification of beverages, which establishes the minimum alcohol content of 8.6 % for the beverage to be considered wine. Therefore, given that the reduction in the water content of grape berries allows the concentration of chemical compounds present in its composition, especially the concentration of total soluble solids, we proceeded with the treatments that were formed by the combination of two temperatures (T1-37.1ºC and T2-22.9 ºC) two air speeds (S1: 1.79 m s-1 and S2: 3.21 m s-1) and a control (T0) that has not gone through the dehydration treatment. Analysis of pH, Total Titratable Acidity (TTA) were performed in mEq L-1, Total Soluble Solids (TSS) in ºBrix, water content on a dry basis and Concentration of Phenolic Compounds (CPC) in mg of gallic acid per 100g of must. The average comparison test identified statistically significant modifications for the adaptation of must for winemaking purposes, having the treatment with 22.9 ºC and air speed of 1.79 m s-1 shown the largest increase in the concentration of total soluble solids, followed by the second best result for concentration of phenolic compounds.

We evaluated the release of rehabilitated, orphan black bears (Ursus americanus) in northern New Hampshire. Eleven bears (9 males, 2 females; 40–45 kg) were outfitted with GPS radio-collars and released during May and June of 2011 and 2012. Bears released in 2011 had higher apparent survival and were not observed or reported in any nuisance behavior, whereas no bears released in 2012 survived, and all were involved in minor nuisance behavior. Analysis of GPS locations indicated that bears in 2011 had access to and used abundant natural forages or habitat. Conversely, abundance of soft and hard mast was lower in 2012, suggesting that nuisance behavior, and consequently survival, was inversely related to availability of natural forage. Dispersal from the release site ranged from 3.4–73 km across both years, and no bear returned to the rehabilitation facility (117 km distance). Rehabilitation appears to be a valid method for addressing certain orphan bear issues in New Hampshire.

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Se valida el nombre genérico Microepidendrum Brieger ex W. E. Higgins, se selecciona un epitipo de Epidendrum subulatifolium A. Rich. et Gal. y se propone la nueva combinación Microepidendrum subulatifolium (A. Rich. et Gal.) W. E. Higgins. Otras especies adscritas por Brieger a Microepidendrum quedan excluidas del grupo. Se presenta una filogenia de la subtribu Laeliinae, en la cual se muestra que Microepidendrum Brieger ex W. E. Higgins es hermano de todos los demás géneros en Laeliinae y no está estrechamente relacionado ni con Epidendrum ni con Encyclia.

PurposeThe Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods.MethodsThe RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages.ResultsThe fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine.ConclusionThe RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.

PurposeThis review is focused on radium and radionuclides in its decay chain in honor of Marie Curie, who discovered this element.Materials and methodsWe conglomerated current knowledge regarding radium and its history predating our present understanding of this radionuclide.ResultsAn overview of the properties of radium and its dose assessment is shown followed by discussions about both the negative detrimental and positive therapeutic applications of radium with this history and its evolution reflecting current innovations in medical science.ConclusionsWe hope to remind all those who are interested in the progress of science about the vagaries of the process of scientific discovery. In addition, we raise the interesting question of whether Marie Curie's initial success was in part possible due to her tight alignment with her husband Pierre Curie who pushed the work along.

In 2018, the National Cancer Institute and NRG Oncology partnered for the first time to host a joint workshop on systemic radiopharmaceutical therapy (RPT) to specifically address dosimetry issues and strategies for future clinical trials. The workshop focused on current dosimetric approaches for clinical trials, strategies under development that would optimize dose reporting, and future desired or optimized approaches for novel emerging radionuclides and carriers in development. In this article, we review the main approaches that are applied clinically to calculate the absorbed dose. These include absorbed doses calculated over a variety of spatial scales, including whole body, organ, suborgan, and voxel, the last 3 of which are achievable within the MIRD schema (S value) and can be calculated with analytic methods or Monte Carlo methods, the latter in most circumstances. This article will also contrast currently available methods and tools with those used in the past, to propose a pathway whereby dosimetry helps the field by optimizing the biologic effect of the treatment and trial design in the drug approval process to reduce financial and logistical costs. We also briefly discuss the dosimetric equivalent of biomarkers to help bring a precision medicine approach to RPT implementation when merited by evidence collected during early-phase trial investigations. Advances in the methodology and related tools have made dosimetry the optimum biomarker for RPT.

Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT. This NRG (acronym formed from the first letter of the 3 original groups: National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group)-National Cancer Institute Working Group review describes some of the challenges to improving RPT. The main priorities for advancing the field include (1) developing and adopting best practice guidelines for incorporating patient-specific dosimetry for RPT that can be used at both large clinics with substantial resources and more modest clinics that have limited resources, (2) establishing and improving strategies for introducing new radiopharmaceuticals for clinical investigation, (3) developing approaches to address the radiophobia that is associated with the administration of radioactivity for cancer therapy, and (4) solving the financial and logistical issues of expertise and training in the developing field of RPT.

We previously reported a family of hydrocarbon-stapled peptides designed to interact with the epidermal growth factor receptor (EGFR) juxtamembrane (JM) segment, blocking its ability to form a coiled coil dimer that is essential for receptor activation. These hydrocarbon-stapled peptides, most notably E1S, decreased the proliferation of cell lines that express wild-type EGFR (H2030 and A431) as well as those expressing the oncogenic mutants EGFR L858R (H3255) and L858R/T790M (H1975). Although our previous investigations provided evidence that E1S interacted with EGFR directly, the location and details of these interactions were not established. Here we apply biochemical and cross-linking mass spectrometry tools to better define the interactions between E1S and EGFR. Taken with previously reported structure-activity relationships, our results support a model in which E1S interacts simultaneously with both the JM and the C-lobe of the activator kinase, effectively displacing the JM of the receiver kinase. Our results also reveal potential interactions between E1S and the N-terminal region of the C-terminal tail. We propose a model in which E1S inhibits EGFR by both mimicking and inhibiting JM coiled coil formation. This model could be used to design novel, allosteric (and perhaps nonpeptidic) EGFR inhibitors.

The area northeast of Sudbury, Ontario, is well known for hosting one of the largest unexplained geophysical anomalies in the Canadian Shield, the Temagami Anomaly. In search of a geological explanation for this anomaly, low-grade metamorphic ultrabasic dykes have been discovered in the overlying Huronian Supergroup sedimentary rocks, both in outcrop and in a deep drill core. Here, we report on the first geochemical and geochronological data obtained on these dykes and compare these data with known magmatic units in and around the 1850 Ma impact-generated Sudbury Igneous Complex (SIC). The NW-striking dykes, which cut across sedimentary rocks of the ca. 2.3 Ga Cobalt Group, and which are, in turn, crosscut by pseudotachylitic breccia, are characterized by distinctively high concentrations of Ti, P, Nb, and Zr, highly fractionated rare earth element patterns (La/[Yb.sub.N] 7.6-15.5), and a lack of crustal contamination (Nb/Th > 10). Such features are typical of modern ocean island basalts but very different from Palaeoproterozoic rocks previously documented in the wider region. Multigrain U-Pb laser ablation inductively coupled plasma mass spectrometry analyses performed on magmatic titanite and apatite with high Th/U ratios yielded 1876.0 [+ or -] 8.7 and 1880.9 [+ or -] 8.3 Ma, respectively, which we interpret as the intrusion age of the dykes. This interpretation is supported by similar whole-rock Sm-Nd model ages of 1890-2000 Ma (initial [[epsilon].sub.Nd] +2.5). This magmatic event in the footwall of the SIC shortly before the impact was coeval with, and likely genetically related to, the 1.88-1.87 Ga Circum-Superior Large Igneous Province. Key words: mafic dykes, titanite dating, apatite dating, Circum-Superior LIP, Cobalt Embayment, Temagami Anomaly, Introduction The giant impact that hit the boundary between the Archaean Superior Province and the Palaeoproterozoic Southern Province at 1850 Ma left behind not only the Sudbury Impact Structure with [...]

BackgroundPedestrian-related injuries are a significant contributor to preventable mortality and disability in children. We hypothesized that interactive pedestrian safety education is associated with increased knowledge, safe crosswalk behaviors, and lower incidence of pedestrian-related injuries in elementary school-aged children.MethodsAn interactive street-crossing simulation was implemented at target elementary schools in Los Angeles County beginning in 2009. Mixed-methods were used to evaluate the impact of this intervention. Multiple-choice examinations were used to test pedestrian safety knowledge, anonymous observations were used to assess street-crossing behaviors, and statewide traffic records were used to report pedestrian injuries in elementary school-aged (4-11 y) children in participating school districts. Pedestrian injury incidence was compared 1 y before and after the intervention, standardized to the incidence in the entire City of Los Angeles.ResultsA total of 1424 and 1522 children completed the pretest and post-test, respectively. Correct answers increased for nine of ten questions (all P

Estimation of absorbed organ doses used in computed tomography (CT) using time-intensive Monte Carlo simulations with virtual patient anatomic models is not widely reported in the literature. Using the library of computational phantoms developed by the University of Florida and the National Cancer Institute, we performed Monte Carlo simulations to calculate organ dose values for 9 CT categories representing the most common body regions and indications for imaging (reflecting low, routine, and high radiation dose examinations), stratified by patient age (in children) and effective diameter (in adults, using "diameter" as a measure of patient size). Our sample of 559,202 adult and 103,423 pediatric CT examinations was prospectively assembled between 2015–2020 from 156 imaging facilities from 27 healthcare organizations in 20 U.S. states and 7 countries in the University of California San Francisco International CT Dose Registry. Organ doses varied by body region and exam type. For example, the mean brain dose associated with head CT was 20 mGy [standard deviation (SD) 14] for head low dose, 46 mGy (SD 21) for head routine dose, and 64 mGy (SD 31) for head high dose scan protocols. The mean colon doses associated with abdomen and pelvis CT were 19 mGy (SD 12), 32 mGy (SD 28), and 69 mGy (SD 42) for low, routine, and high dose examinations, respectively. Organ doses in general varied modestly by patient diameter, and for many categories the organ doses among the largest quartile of patients were no more than 10% higher than doses in the smallest quartile. For example, for abdomen and pelvis high dose, the colon dose increased from 67 to 74 mGy from the smallest to the largest patients (10% increase). With few exceptions, pediatric organ doses also varied relatively little by patient age, except for the youngest children who, on average, had higher organ doses. Thyroid dose, however, tended to increase with age in neck or cervical spine and chest CT. Overall, the highest organ doses were to the skin, thyroid, brain, and eye lens. Mean organ doses differ substantially by site. The organ dose values included in this report are derived from empirical clinical exams and offer useful, representative values. Large inter-site variations demonstrate areas for radiation dose reduction. [ABSTRACT FROM AUTHOR]