Patient-specific quality assurance of dynamically-collimated proton therapy treatment plans.

BACKGROUND: The dynamic collimation system (DCS) provides energy layer-specific collimation for pencil beam scanning (PBS) proton therapy using two pairs of orthogonal nickel trimmer blades. While excellent measurement-to-calculation agreement has been demonstrated for simple cube-shaped DCS-trimmed dose distributions, no comparison of measurement and dose calculation has been made for patient-specific treatment plans. PURPOSE: To validate a patient-specific quality assurance (PSQA) process for DCS-trimmed PBS treatment plans and evaluate the agreement between measured and calculated dose distributions. METHODS: Three intracranial patient cases were considered. Standard uncollimated PBS and DCS-collimated treatment plans were generated for each patient using the Astroid treatment planning system (TPS). Plans were recalculated in a water phantom and delivered at the Miami Cancer Institute (MCI) using an Ion Beam Applications (IBA) dedicated nozzle system and prototype DCS. Planar dose measurements were acquired at two depths within low-gradient regions of the target volume using an IBA MatriXX ion chamber array. RESULTS: Measured and calculated dose distributions were compared using 2D gamma analysis with 3%/3 mm criteria and low dose threshold of 10% of the maximum dose. Median gamma pass rates across all plans and measurement depths were 99.0% (PBS) and 98.3% (DCS), with a minimum gamma pass rate of 88.5% (PBS) and 91.2% (DCS). CONCLUSIONS: The PSQA process has been validated and experimentally verified for DCS-collimated PBS. Dosimetric agreement between the measured and calculated doses was demonstrated to be similar for DCS-collimated PBS to that achievable with noncollimated PBS.

Transferability and Accuracy of Ionic Liquid Simulations with Equivariant Machine Learning Interatomic Potentials.

Ionic liquids (ILs) are an exciting class of electrolytes finding applications in many areas from energy storage to solvents, where they have been touted as "designer solvents" as they can be mixed to precisely tailor the physiochemical properties. As using machine learning interatomic potentials (MLIPs) to simulate ILs is still relatively unexplored, several questions need to be answered to see if MLIPs can be transformative for ILs. Since ILs are often not pure, but are either mixed together or contain additives, we first demonstrate that a MLIP can be trained to be compositionally transferable; i.e., the MLIP can be applied to mixtures of ions not directly trained on, while only being trained on a few mixtures of the same ions. We also investigated the accuracy of MLIPs for a novel IL, which we experimentally synthesize and characterize. Our MLIP trained on ∼200 DFT frames is in reasonable agreement with our experiments and DFT.

Effects of Harmful Algal Blooms on Amphibians and Reptiles are Under-Reported and Under-Represented.

Harmful algal blooms (HABs) are a persistent and increasing problem globally, yet we still have limited knowledge about how they affect wildlife. Although semi-aquatic and aquatic amphibians and reptiles have experienced large declines and occupy environments where HABs are increasingly problematic, their vulnerability to HABs remains unclear. To inform monitoring, management, and future research, we conducted a literature review, synthesized the studies, and report on the mortality events describing effects of cyanotoxins from HABs on freshwater herpetofauna. Our review identified 37 unique studies and 71 endpoints (no-observed-effect and lowest-observed-effect concentrations) involving 11 amphibian and 3 reptile species worldwide. Responses varied widely among studies, species, and exposure concentrations used in experiments. Concentrations causing lethal and sublethal effects in laboratory experiments were generally 1 to 100 µg/L, which contains the mean value of reported HAB events but is 70 times less than the maximum cyanotoxin concentrations reported in the environment. However, one species of amphibian was tolerant to concentrations of 10,000 µg/L, demonstrating potentially immense differences in sensitivities. Most studies focused on microcystin-LR (MC-LR), which can increase systemic inflammation and harm the digestive system, reproductive organs, liver, kidneys, and development. The few studies on other cyanotoxins illustrated that effects resembled those of MC-LR at similar concentrations, but more research is needed to describe effects of other cyanotoxins and mixtures of cyanotoxins that commonly occur in the environment. All experimental studies were on larval and adult amphibians; there were no such studies on reptiles. Experimental work with reptiles and adult amphibians is needed to clarify thresholds of tolerance. Only nine mortality events were reported, mostly for reptiles. Given that amphibians likely decay faster than reptiles, which have tissues that resist decomposition, mass amphibian mortality events from HABs have likely been under-reported. We propose that future efforts should be focused on seven major areas, to enhance our understanding of effects and monitoring of HABs on herpetofauna that fill important roles in freshwater and terrestrial environments. Environ Toxicol Chem 2024;00:1-14. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Developing Confidence in Engaging in Diversity, Equity, and Inclusion and Social Determinants of Health Topics Through Self-Authorship.

OBJECTIVE: This study used a self-authorship framework to explore if diversity, equity, and inclusion (DEI) and social determinants of health (SDoH)-focused laboratories and learning activities increase student confidence in understanding aspects of implicit bias and SDoH, and how these activities impact student comfort in discussing and confidence in initiating conversations on DEI/SDoH topics with colleagues, faculty, supervisors, and patients. METHODS: First-year PharmD students engaged in 3 learning activities across 2 courses. Students were challenged to evaluate their biases and incorporate DEI/SDoH into their professional identity formation. This study used a mixed-methods, embedded approach to analyze assessment data collected via a questionnaire and assignments administered at 3 points during the fall semester. Quantitative analysis used a quasi-experimental, between-participants, pretest-posttest design. The qualitative component used open-ended questions to gain additional insight into participant experiences, gathered detail on perceptions, and provided context. RESULTS: A 1-way analysis of variance showed statistically significant increases between assessment points for all items related to confidence in understanding implicit bias and SDoH. Comfort in discussing DEI/SDoH topics with supervisors/faculty and patients increased over time. Comfort in discussing DEI/SDoH topics with colleagues did not increase. Three salient themes emerged from qualitative analyses: bias and privilege awareness, education, and professionalism. CONCLUSION: This study found that students started evaluating their own knowledge, beliefs, and claims in social and professional settings as defined by the self-authorship framework. Student comfort and confidence in discussing DEI/SDoH topics increased over time. Findings support that engaging students in multimodal programming may support incorporation of DEI/SDoH into professional identity formation.

Untargeted metabolomics reveal signatures of a healthy lifestyle.

This cross-sectional study investigated differences in the plasma metabolome in two groups of adults that were of similar age but varied markedly in body composition and dietary and physical activity patterns. Study participants included 52 adults in the lifestyle group (LIFE) (28 males, 24 females) and 52 in the control group (CON) (27 males, 25 females). The results using an extensive untargeted ultra high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) metabolomics analysis with 10,535 metabolite peaks identified 486 important metabolites (variable influence on projections scores of VIP ≥ 1) and 16 significantly enriched metabolic pathways that differentiated LIFE and CON groups. A novel metabolite signature of positive lifestyle habits emerged from this analysis highlighted by lower plasma levels of numerous bile acids, an amino acid profile characterized by higher histidine and lower glutamic acid, glutamine, ß-alanine, phenylalanine, tyrosine, and proline, an elevated vitamin D status, higher levels of beneficial fatty acids and gut microbiome catabolism metabolites from plant substrates, and reduced levels of N-glycan degradation metabolites and environmental contaminants. This study established that the plasma metabolome is strongly associated with body composition and lifestyle habits. The robust lifestyle metabolite signature identified in this study is consistent with an improved life expectancy and a reduced risk for chronic disease.

Studying interactions among anthropogenic stressors in freshwater ecosystems: A systematic review of 2396 multiple-stressor experiments.

Understanding the interactions among anthropogenic stressors is critical for effective conservation and management of ecosystems. Freshwater scientists have invested considerable resources in conducting factorial experiments to disentangle stressor interactions by testing their individual and combined effects. However, the diversity of stressors and systems studied has hindered previous syntheses of this body of research. To overcome this challenge, we used a novel machine learning framework to identify relevant studies from over 235,000 publications. Our synthesis resulted in a new dataset of 2396 multiple-stressor experiments in freshwater systems. By summarizing the methods used in these studies, quantifying trends in the popularity of the investigated stressors, and performing co-occurrence analysis, we produce the most comprehensive overview of this diverse field of research to date. We provide both a taxonomy grouping the 909 investigated stressors into 31 classes and an open-source and interactive version of the dataset (https://jamesaorr.shinyapps.io/freshwater-multiple-stressors/). Inspired by our results, we provide a framework to help clarify whether statistical interactions detected by factorial experiments align with stressor interactions of interest, and we outline general guidelines for the design of multiple-stressor experiments relevant to any system. We conclude by highlighting the research directions required to better understand freshwater ecosystems facing multiple stressors.

Synthesis of Monofluorinated 7-Hydroxycoumarin-3-Carboxamides as Cell-Permeable Fluorescent Molecular Probes.

To facilitate studies of engagement of protein targets by small molecules in living cells, we synthesized fluorinated derivatives of the fluorophore 7-hydroxycoumarin-3-carboxylic acid (7OHCCA). Compared to the related difluorinated coumarin Pacific Blue (PB), amide derivatives of 6-fluoro-7-hydroxycoumarin-3-carboxylic acid (6FC) exhibited substantially brighter fluorescence. When linked to the anticancer drug paclitaxel (Taxol) via gamma-aminobutyric acid (GABA), the acidity of the phenol of these coumarins profoundly affected cellular efflux and binding to microtubules in living cells. In contrast to the known fluorescent taxoid PB-GABA-Taxol, the less acidic 6FC-GABA-Taxol was more cell-permeable due to a lower susceptibility to active efflux. In living cells, this facilitated the imaging of microtubules by confocal microscopy and enabled quantification of binding to microtubules by flow cytometry without added efflux inhibitors. The photophysical, chemical, and biological properties of 6FC derivatives make these compounds particularly attractive for the construction of fluorescent molecular probes suitable for quantitative analysis of intracellular small molecule-protein interactions.

Examining the Potential of Pharmacies to Expand Pre-Exposure Prophylaxis Access Along Georgia's Fixed-Route Public Transit: A Geospatial Analysis.

BACKGROUND: Despite accounting for more than half of new Human Immunodeficiency Virus diagnoses in the United States, the South has fewer than 30% of all pre-exposure prophylaxis users. Pre-exposure prophylaxis access geospatial analyses have focused on drive time but analyses along public transit routes have not been evaluated. Given the proximity to pharmacists and pharmacies, involvement in pre-exposure prophylaxis services may increase access and uptake of this preventative health need. OBJECTIVE: The objectives were to compare the rate of pre-exposure prophylaxis uptake between Georgia counties with and without public transit, to assess the geospatial accessibility of services along public transit, and to evaluate the potential impact of expanding pre-exposure prophylaxis services to community pharmacies. METHODS: Pre-exposure prophylaxis uptake rates between counties with and without public transit were compared using the Mann-Whitney U test. Geospatial analysis was performed using ArcGIS Pro and Geoda. The Pearson correlation coefficient was used to determine the relationship between pre-exposure prophylaxis uptake rates and population and county characteristics. Spatial analysis was completed to uncover predictors for pre-exposure prophylaxis uptake rates. Increased access to pre-exposure prophylaxis along public transit was calculated by reporting the number of counties that would experience at least a 50% increase in pre-exposure prophylaxis access through community pharmacies. RESULTS: Pre-exposure prophylaxis uptake is significantly higher in Georgia counties with versus without public transit (P < 0.001). Pre-exposure prophylaxis rate is positively correlated with the accessibility of community pharmacies and pre-exposure prophylaxis clinics along fixed-route public transit (R2 = 0.524). Among pre-exposure prophylaxis clinics, 44% are inaccessible by public transit alone. Community pharmacies are significantly more widely distributed and accessible along public transit routes than pre-exposure prophylaxis clinics. CONCLUSION: Transportation remains a barrier to accessing pre-exposure prophylaxis. Georgia community pharmacies along public transit may serve as a solution to pre-exposure prophylaxis care access barriers.

A re-activation model for 169Yb intensity modulated brachytherapy sources accounting for spatiotemporal isotopic composition.

BACKGROUND: Intensity modulated brachytherapy based on partially shielded intracavitary and interstitial applicators is possible with a cost-effective 169Yb production method. 169Yb is a traditionally expensive isotope suitable for this purpose, with an average γ-ray energy of 93 keV. Re-activating a single 169Yb source multiple times in a nuclear reactor between clinical uses was shown to theoretically reduce cost by approximately 75% relative to conventional single-activation sources. With re-activation, substantial spatiotemporal variation in isotopic source composition is expected between activations via 168Yb burnup and 169Yb decay, resulting in time dependent neutron transmission, precursor usage, and reactor time needed per re-activation. PURPOSE: To introduce a generalized model of radioactive source production that accounts for spatiotemporal variation in isotopic source composition to improve the efficiency estimate of the 169Yb production process, with and without re-activation. METHODS AND MATERIALS: A time-dependent thermal neutron transport, isotope transmutation, and decay model was developed. Thermal neutron flux within partitioned sub-volumes of a cylindrical active source was calculated by raytracing through the spatiotemporal dependent isotopic composition throughout the source, accounting for thermal neutron attenuation along each ray. The model was benchmarked, generalized, and applied to a variety of active source dimensions with radii ranging from 0.4 to 1.0 mm, lengths from 2.5 to 10.5 mm, and volumes from 0.31 to 7.85 mm3, at thermal neutron fluxes from 1 × 1014 to 1 × 1015 n cm-2 s-1. The 168Yb-Yb2O3 density was 8.5 g cm-3 with 82% 168Yb-enrichment. As an example, a reference re-activatable 169Yb active source (RRS) constructed of 82%-enriched 168Yb-Yb2O3 precursor was modeled, with 0.6 mm diameter, 10.5 mm length, 3 mm3 volume, 8.5 g cm-3 density, and a thermal neutron activation flux of 4 × 1014 neutrons cm-2 s-1. RESULTS: The average clinical 169Yb activity for a 0.99 versus 0.31 mm3 source dropped from 20.1 to 7.5 Ci for a 4 × 1014 n cm-2 s-1 activation flux and from 20.9 to 8.7 Ci for a 1 × 1015 n cm-2 s-1 activation flux. For thermal neutron fluxes ≥2 × 1014 n cm-2 s-1, total precursor and reactor time per clinic-year were maximized at a source volume of 0.99 mm3 and reached a near minimum at 3 mm3. When the spatiotemporal isotopic composition effect was accounted for, average thermal neutron transmission increased over RRS lifetime from 23.6% to 55.9%. A 28% reduction (42.5 days to 30.6 days) in the reactor time needed per clinic-year for the RRS is predicted relative to a model that does not account for spatiotemporal isotopic composition effects. CONCLUSIONS: Accounting for spatiotemporal isotopic composition effects within the RRS results in a 28% reduction in the reactor time per clinic-year relative to the case in which such changes are not accounted for. Smaller volume sources had a disadvantage in that average clinical 169Yb activity decreased substantially below 20 Ci for source volumes under 1 mm3. Increasing source volume above 3 mm3 adds little value in precursor and reactor time savings and has a geometric disadvantage.

Technical note: A simple method for patient-specific quality assurance for lateral targets on a 1.5 T MR-Linac.

The Elekta Unity magnetic resonance (MR) linac is limited to longitudinal couch motion and a sagittal-only laser, which restricts the ability to perform patient-specific quality assurance (PSQA) intensity-modulated radiotherapy (IMRT) measurements for very lateral targets. This work introduces a simple method to perform PSQA using the Sun Nuclear ArcCheck-MR phantom at left and right lateral positions without additional equipment or in-house construction. The proposed setup places the center of the phantom 1.3 cm vertical and 12.9 cm lateral to isocenter in either the left or right direction. Computed tomography (CT) scans are used to simulate the setup and create a QA plan template in the Monaco treatment planning system (TPS). The workflow is demonstrated for four patients, with an average axial distance from the center of the bore to the planning target volume (PTV) of 12.4 cm. Gamma pass rates were above 94% for all plans using global 3%/2 mm gamma criterion with a 10% threshold. Setup uncertainties are slightly larger for the proposed lateral setup compared to the centered setup on the Elekta platform (∼1 mm compared to ∼0.5 mm), but acceptable pass rates are achievable without optimizing shifts in the gamma analysis software. In general, adding the left and right lateral positions increases the axial area in the bore encompassed by the cylindrical measurement array by 147%, substantially increasing the flexibility of measurements for offset targets. Based on this work, we propose using the lateral QA setup if the closest distance to the PTV edge from isocenter is larger than the array radius (10.5 cm) or the percent of the PTV encompassed by the diode array would be increased with the lateral setup compared to the centered setup.

Collaborative drug therapy modification (CDTM): Facilitators, barriers, and perceptions of individual pharmacist participation in Georgia.

BACKGROUND: Georgia Board of Pharmacy (BOP) regulations permit pharmacists to engage in collaborative drug therapy modification (CDTM) with physicians, allowing them to perform patient assessments, adjust pharmacotherapy, and order laboratory tests. Pharmacist-led CDTM can positively affect health outcomes leading to reduced healthcare expenditures. CDTM is underutilized, with < 1% of Georgia pharmacists holding an active license to practice CDTM. OBJECTIVE(S): The objective of this study was to examine CDTM licensed pharmacists' perceptions of facilitators and barriers in providing CDTM. METHODS: Georgia-licensed CDTM pharmacists were invited to participate in a 60-minute qualitative interview. Interview questions were developed from electronic survey responses. The interview was designed to elicit information regarding perceived benefits and barriers to CDTM implementation. Guided by the Consolidated Framework for Implementation Research, thematic analysis was applied to identify themes using ATLAS.ti software to code. Themes were described qualitatively and prevalence of each was reported. RESULTS: Nine interviews were conducted, and data saturation was achieved at interview 6. After resolution of discrepancies, 100% coding agreement was reached among 2 independent researchers. Nine themes were identified, and each was categorized as a facilitator or barrier to establishing pharmacist-led CDTM in Georgia. Themes associated with facilitating were (prevalence %) (1) practice autonomy (100), (2) personal attributes (100), (3) having support (100), and (4) institutional logistics (88). Barrier themes included issues concerning (5) the Georgia BOP (100), (6) pharmacist autonomy (88), (7) lack of provider status (88), (8) institutional restrictions (75), and (9) personal development (e.g., confidence) (22). CONCLUSION: Facilitators to the establishment of pharmacist-led CDTM exist and pharmacists can capitalize on these to create successful CDTM programs. Barriers are varied, and it may be difficult to systematically address individual barriers such as pharmacist autonomy and personal development. Barriers associated with institutional restrictions, the Georgia BOP, and lack of provider status can likely be removed or addressed by policy.

Further delineation of the phenotypic and metabolomic profile of ALDH1L2-related neurodevelopmental disorder.

ALDH1L2, a mitochondrial enzyme in folate metabolism, converts 10-formyl-THF (10-formyltetrahydrofolate) to THF (tetrahydrofolate) and CO2. At the cellular level, deficiency of this NADP+-dependent reaction results in marked reduction in NADPH/NADP+ ratio and reduced mitochondrial ATP. Thus far, a single patient with biallelic ALDH1L2 variants and the phenotype of a neurodevelopmental disorder has been reported. Here, we describe another patient with a neurodevelopmental disorder associated with a novel homozygous missense variant in ALDH1L2, Pro133His. The variant caused marked reduction in the ALDH1L2 enzyme activity in skin fibroblasts derived from the patient as probed by 10-FDDF, a stable synthetic analog of 10-formyl-THF. Additional associated abnormalities in these fibroblasts include reduced NADPH/NADP+ ratio and pool of mitochondrial ATP, upregulated autophagy and dramatically altered metabolomic profile. Overall, our study further supports a link between ALDH1L2 deficiency and abnormal neurodevelopment in humans.

A Dataset of Amphibian Species in U.S. National Parks.

National parks and other protected areas are important for preserving landscapes and biodiversity worldwide. An essential component of the mission of the United States (U.S.) National Park Service (NPS) requires understanding and maintaining accurate inventories of species on protected lands. We describe a new, national-scale synthesis of amphibian species occurrence in the NPS system. Many park units have a list of amphibian species observed within their borders compiled from various sources and available publicly through the NPSpecies platform. However, many of the observations in NPSpecies remain unverified and the lists are often outdated. We updated the amphibian dataset for each park unit by collating old and new park-level records and had them verified by regional experts. The new dataset contains occurrence records for 292 of the 424 NPS units and includes updated taxonomy, international and state conservation rankings, hyperlinks to a supporting reference for each record, specific notes, and related fields which can be used to better understand and manage amphibian biodiversity within a single park or group of parks.

Implementing an adaptive, two-tiered SARS-CoV-2 wastewater surveillance program on a university campus using passive sampling.

Building-level wastewater-based surveillance (WBS) has been increasingly applied upstream from wastewater treatment plants to conduct targeted monitoring for SARS-CoV-2. In this study, a two-tiered, trigger-based wastewater surveillance program was developed on a university campus to monitor dormitory wastewater. The objective was to determine if passive sampling with cotton gauze as a sampling medium could be used to support institution-level public health action. Two nucleocapsid gene targets (N1 and N2) of SARS-CoV-2 as well as the endogenous fecal indicator pepper mild mottle virus (PMMoV) were quantified using RT-qPCR. >500 samples were analyzed during two contrasting surveillance periods. In the Fall of 2021 community viral burden was low and a tiered sampling network was able to isolate individual clinical cases at the building-scale. In the Winter of 2022 wastewater signals were quickly elevated by the emergence of the highly transmissible SARS-CoV-2 Omicron (B.1.1.529) variant. Prevalence of SARS-CoV-2 shifted surveillance objectives from isolating cases to monitoring trends, revealing both the benefits and limitations of a tiered surveillance design under different public health situations. Normalization of SARS-CoV-2 by PMMoV was not reflective of upstream population differences, suggesting saturation of the material occurred during the exposure period. The passive sampling method detected nearly all known clinical cases and in one instance was able to identify one pre-symptomatic individual days prior to confirmation by clinical test. Comparisons between campus samplers and municipal wastewater influent suggests that the spread of COVID-19 on the campus was similar to that of the broader community. The results demonstrate that passive sampling is an effective tool that can produce semi-quantitative data capable of tracking temporal trends to guide targeted public health decision-making at an institutional level. Practitioners of WBS can utilize these results to inform surveillance program designs that prioritize efficient resource use and rapid reporting.

Quantification of Binding of Small Molecules to Native Proteins Overexpressed in Living Cells.

The affinity and selectivity of small molecules for proteins drive drug discovery and development. We report a fluorescent probe cellular binding assay (FPCBA) for determination of these values for native (untagged) proteins overexpressed in living cells. This method uses fluorophores such as Pacific Blue (PB) linked to cell-permeable protein ligands to generate probes that rapidly and reversibly equilibrate with intracellular targets, as established by kinetic assays of cellular uptake and efflux. To analyze binding to untagged proteins, an internal ribosomal entry site (IRES) vector was employed that allows a single mRNA to encode both the protein target and a separate orthogonal fluorescent protein (mVenus). This enabled cellular uptake of the probe to be correlated with protein expression by flow cytometry, allowing measurement of cellular dissociation constants (Kd) of the probe. This approach was validated by studies of the binding of allosteric activators to eight different Protein Kinase C (PKC) isozymes. Full-length PKCs expressed in transiently transfected HEK293T cells were used to measure cellular Kd values of a probe comprising PB linked to the natural product phorbol via a carbamate. These values were further used to determine competitive binding constants (cellular Ki values) of the nonfluorescent phorbol ester PDBu and the anticancer agent bryostatin 1 for each isozyme. For some PKC-small molecule pairs, these cellular Ki values matched known biochemical Ki values, but for others, altered selectivity was observed in cells. This approach can facilitate quantification of interactions of small molecules with physiologically relevant native proteins.

Survey of Georgia community pharmacists' needs to engage in advanced community pharmacy services.

BACKGROUND: Community pharmacists improve health, reduce fragmentation in care, lower health costs, and improve health outcomes. In Georgia, pharmacists are able to enter collaborative drug therapy management protocols, such as hypertension management, with a collaborating physician, which may allow pharmacists to provide advanced community pharmacy services (ACPS), however few Georgia pharmacists have this licensure. No program(s) exist that empower pharmacists to successfully engage in ACPS across the state of Georgia nor trains pharmacists to successfully engage in collaborative practice. OBJECTIVE: The goal of this project was to explore community pharmacists' perception, confidence, and engagement in ACPS and how this can improve access to care in Georgia. METHODS: Six hundred one independent community pharmacists were sent an electronic survey May 13, 2022, with weekly email reminders through June 17, 2022. Results were analyzed with the independent sample t test. Thematic analysis was completed on open response survey questions. RESULTS: Ninety responses were received (15% response rate). In the majority of survey outcomes, no differences were found in needs for success between rural versus urban pharmacists. Pharmacies with a smaller technician-to-pharmacists ≤2 (staffing) ratios identified billing for services as a higher priority need for success for them to confidently engage in ACPS (P = 0.012) while pharmacies with a higher technician-to-pharmacists >2 (staffing) ratio agreed a larger need was in optimization of current workflow to allow for advanced community pharmacy service incorporation (P = 0.034). All community pharmacists agreed they would require expansion in staffing and the qualities desired for additional hires to support ACPS include ambition, proficiency, and communication skills. CONCLUSION: Numerous needs for success exist for community pharmacists to feel comfortable and confident to engage in ACPS. Addressing these needs may increase community pharmacist impact through increasing utilization of these services.

Assay validation of saliva glucocorticoids in Columbia spotted frogs and effects of handling and marking.

Non-invasive methods are important to the field of conservation physiology to reduce negative effects on organisms being studied. Glucocorticoid (GC) hormones are often used to assess health of individuals, but collection methods can be invasive. Many amphibians are imperiled worldwide, and saliva is a non- or semi-invasive matrix to measure GCs that has been partially validated for only four amphibian species. Validation ensures that assays are reliable and can detect changes in saliva corticosterone (sCORT) after exposure to stressors, but it is also necessary to ensure sCORT concentrations are correlated with plasma concentrations. To help validate the use of saliva in assessing CORT responses in amphibians, we captured uniquely marked Columbia spotted frogs (Rana luteiventris) on sequential days and collected baseline and stress-induced (after handling) samples. For a subset of individuals, we collected and quantified CORT in both saliva and blood samples, which have not been compared for amphibians. We tested several aspects of CORT responses and, by collecting across separate days, measured repeatability of CORT responses across days. We also evaluated whether methods common to amphibian conservation, such as handling alone or handling, clipping a toe and tagging elevated sCORT. Similar to previous studies, we show that sCORT is reliable concerning parallelism, recovery, precision and sensitivity. sCORT was weakly correlated with plasma CORT (R2 = 0.21), and we detected elevations in sCORT after handling, demonstrating biological validation. Toe clipping and tagging did not increase sCORT over handling alone, but repeated handling elevated sCORT for ~72 hours. However, sCORT responses were highly variable and repeatability was low within individuals and among capture sessions, contrary to previous studies with urinary and waterborne CORT. sCORT is a semi-invasive and rapid technique that could be useful to assess effects of anthropogenic change and conservation efforts, but will require careful study design and future validation.

Broad-Scale Assessment of Methylmercury in Adult Amphibians.

Mercury (Hg) is a toxic contaminant that has been mobilized and distributed worldwide and is a threat to many wildlife species. Amphibians are facing unprecedented global declines due to many threats including contaminants. While the biphasic life history of many amphibians creates a potential nexus for methylmercury (MeHg) exposure in aquatic habitats and subsequent health effects, the broad-scale distribution of MeHg exposure in amphibians remains unknown. We used nonlethal sampling to assess MeHg bioaccumulation in 3,241 juvenile and adult amphibians during 2017-2021. We sampled 26 populations (14 species) across 11 states in the United States, including several imperiled species that could not have been sampled by traditional lethal methods. We examined whether life history traits of species and whether the concentration of total mercury in sediment or dragonflies could be used as indicators of MeHg bioaccumulation in amphibians. Methylmercury contamination was widespread, with a 33-fold difference in concentrations across sites. Variation among years and clustered subsites was less than variation across sites. Life history characteristics such as size, sex, and whether the amphibian was a frog, toad, newt, or other salamander were the factors most strongly associated with bioaccumulation. Total Hg in dragonflies was a reliable indicator of bioaccumulation of MeHg in amphibians (R2 ≥ 0.67), whereas total Hg in sediment was not (R2 ≤ 0.04). Our study, the largest broad-scale assessment of MeHg bioaccumulation in amphibians, highlights methodological advances that allow for nonlethal sampling of rare species and reveals immense variation among species, life histories, and sites. Our findings can help identify sensitive populations and provide environmentally relevant concentrations for future studies to better quantify the potential threats of MeHg to amphibians.

Integration and dosimetric validation of a dynamic collimation system for pencil beam scanning proton therapy.

Objective.To integrate a Dynamic Collimation System (DCS) into a pencil beam scanning (PBS) proton therapy system and validate its dosimetric impact.Approach.Uncollimated and collimated treatment fields were developed for clinically relevant targets using an in-house treatment plan optimizer and an experimentally validated Monte Carlo model of the DCS and IBA dedicated nozzle (DN) system. The dose reduction induced by the DCS was quantified by calculating the mean dose in 10- and 30-mm two-dimensional rinds surrounding the target. A select number of plans were then used to experimentally validate the mechanical integration of the DCS and beam scanning controller system through measurements with the MatriXX-PT ionization chamber array and EBT3 film. Absolute doses were verified at the central axis at various depths using the IBA MatriXX-PT and PPC05 ionization chamber.Main results.Simulations demonstrated a maximum mean dose reduction of 12% for the 10 mm rind region and 45% for the 30 mm rind region when utilizing the DCS. Excellent agreement was observed between Monte Carlo simulations, EBT3 film, and MatriXX-PT measurements, with gamma pass rates exceeding 94.9% for all tested plans at the 3%/2 mm criterion. Absolute central axis doses showed an average verification difference of 1.4% between Monte Carlo and MatriXX-PT/PPC05 measurements.Significance.We have successfully dosimetrically validated the delivery of dynamically collimated proton therapy for clinically relevant delivery patterns and dose distributions with the DCS. Monte Carlo simulations were employed to assess dose reductions and treatment planning considerations associated with the DCS.