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Purpose We investigated the hypothesis that the transmission function of rounded end linearly traveling multileaf collimators (MLCs) is constant with position. This assumption is made by some MLC models used in clinical treatment planning systems (TPSs) and in the Varian MLC calibration convention. If not constant, this would have implications for treatment plan QA results. Methods A two‐dimensional ray‐tracing tool to generate transmission curves as a function of leaf position was created and validated. The curves for clinically available leaf tip positions (−20 to 20 cm) were analyzed to determine the location of the beam edge (half‐attenuation X‐ray [XR]) location, the beam edge broadening (BEB, 80%–20% width), as well as the leaf tip zone width. More generalized scenarios were then simulated to elucidate trends as a function of leaf tip radius. Results In the analysis of the Varian high‐definition MLC, two regions were identified: a quasi‐static inner region centered about central axis (CAX), and an outer one, in which large deviations were observed. A phenomenon was identified where the half‐attenuation ray position, relative to that of the tip or tangential ray, increases dramatically at definitive points from CAX. Similar behavior is seen for BEB. An analysis shows that as the leaf radius parameter value is made smaller, the size of the quasi‐static region is greater (and vice versa). Conclusion The MLC transmission curve properties determined by this study have implications both for MLC position calibrations and modeling within TPSs. Two‐dimensional ray tracing can be utilized to identify where simple behaviors hold, and where they deviate. These results can help clinical physicists engage with vendors to improve MLC models, subsequent fluence calculations, and hence dose calculation accuracy.

Mercury (Hg) from Hg mining at Clear Lake, California, USA, has contaminated water and sediments for over 130 years and has the potential to affect human and environmental health. With total mercury (TotHg) concentrations up to 438 mg/kg (dry mass) in surficial sediments and up to 399 ng/L in lake water, Clear Lake is one of the most Hg‐contaminated lakes worldwide. Particulate Hg in surface water near the mine ranges from 10 000 to 64 000 ng/g; TotHg declines exponentially with distance from the Sulphur Bank Mercury Mine. From 1992 to 1998, no significant long‐term trends for TotHg or methylmercury (MeHg) in sediments or water were observed, but peaks of both TotHg and MeHg occurred following a 1995 flooding event. Sediments and water exhibit summer/fall maxima and winter/spring minima for MeHg, but not TotHg. Sediment TotHg has not declined significantly a decade after remediation in 1992. At the mine site, aqueous TotHg reached 374 000 ng/L in unfiltered groundwater. Pore water sulfate in sediments varies seasonally from 112 mg/L in summer/fall (when Hg methylation is highest) to 3300 mg/L in winter. While TotHg is exceptionally high in both sediments and water, MeHg is substantially lower than would be expected based on the bulk Hg loading to the lake and in comparison with other sites worldwide. Total mercury in Clear Lake water does not exceed the Safe Drinking Water Act criteria, but it sometimes greatly exceeds human health criteria established by the Great Lakes Initiative, U.S. Environmental Protection Agency water quality guidelines, and the California Toxics Rule criterion. Methylmercury concentrations exceed the Great Lakes Initiative criterion for MeHg in water at some sites only during summer/fall. Relative to ecological health, Clear Lake sediments greatly exceed the National Oceanic and Atmospheric Administration's benthic fauna Sediment Quality Guidelines for toxic effects, as well as the more concensus‐based Threshold Effects Concentration criteria. Based on these criteria, Hg‐contaminated sediments and water from Clear Lake are predicted to have some lethal and sublethal effects on specific resident aquatic species. However, based on unique physical and chemical characteristics of the Clear Lake environment, MeHg toxicity may be significantly less than anticipated from the large inorganic Hg loading.

Clear Lake is the site of an abandoned mercury (Hg) mine (active intermittently from 1873 to 1957), now a U.S. Environmental Protection Agency Superfund Site. Mining activities, including bulldozing waste rock and tailings into the lake, resulted in ∼100 Mg of Hg entering the lake's ecosystem. This series of papers represents the culmination of ∼15 years of Hg‐related studies on this ecosystem, following Hg from the ore body to the highest trophic levels. A series of physical, chemical, biological, and limnological studies elucidate how ongoing Hg loading to the lake is influenced by acid mine drainage and how wind‐driven currents and baroclinic circulation patterns redistribute Hg throughout the lake. Methylmercury (MeHg) production in this system is controlled by both sulfate‐reducing bacteria as well as newly identified iron‐reducing bacteria. Sediment cores (dated with dichlorodiphenyldichlorethane [DDD], ²¹⁰Pb, and ¹⁴C) to ∼250 cm depth (representing up to ∼3000 years before present) elucidate a record of total Hg (TotHg) loading to the lake from natural sources and mining and demonstrate how MeHg remains stable at depth within the sediment column for decades to millenia. Core data also identify other stresses that have influenced the Clear Lake Basin especially over the past 150 years. Although Clear Lake is one of the most Hg‐contaminated lakes in the world, biota do not exhibit MeHg concentrations as high as would be predicted based on the gross level of Hg loading. We compare Clear Lake's TotHg and MeHg concentrations with other sites worldwide and suggest several hypotheses to explain why this discrepancy exists. Based on our data, together with state and federal water and sediment quality criteria, we predict potential resulting environmental and human health effects and provide data that can assist remediation efforts.

Background Quality assurance measurement of IMRT/VMAT treatment plans is resource intensive, and other more efficient methods to achieve the same confidence are desirable. Purpose We aimed to analyze treatment plans in the context of the treatment planning systems that created them, in order to predict which ones will fail a standard quality assurance measurement. To do so, we sought to create a tool external to the treatment planning system that could analyze a set of MLC positions and provide information that could be used to calculate various evaluation metrics. Methods The tool was created in Python to read in DICOM plan files and determine the beam fluence fraction incident on each of seven different zones, each classified based on the RayStation MLC model. The fractions, termed grid point fractions, were validated by analyzing simple test plans. The average grid point fractions, over all control points for 46 plans were then computed. These values were then compared with gamma analysis pass percentages and median dose differences to determine if any significant correlations existed. Results Significant correlation was found between the grid point fraction metrics and median dose differences, but not with gamma analysis pass percentages. Correlations were positive or negative, suggesting differing model parameter value sensitivities, as well as potential insight into the treatment planning system dose model. Conclusions By decomposing MLC control points into different transmission zones, it is possible to create a metric that predicts whether the analyzed plan will pass a quality assurance measurement from a dose calculation accuracy standpoint. The tool and metrics developed in this work have potential applications in comparing clinical beam models or identifying their weak points. Implementing the tool within a treatment planning system would also provide more potential plan optimization parameters.

Purpose A single treatment planning system (TPS) model for matched linacs provides flexible clinical workflows from patient treatment to intensity‐modulated radiation therapy (IMRT) quality assurance (QA) measurement. Since general guidelines for building a single TPS model and its validation for matched linacs are not well established, we present our RayStation photon TPS modeling strategy for matched Elekta VersaHD linacs. Method The four linacs installed from 2013 to 2020 were matched in terms of Percent Depth Dose (PDD), profile, output factor and wedge factors for 6‐MV, 10‐MV, 15‐MV, and 6‐MV‐FFF, and maintained following TG‐142 recommendations until RayStation commissioning. The RayStation single model was built to represent all four linacs within the tolerance limits recommended by MPPG‐5.a. The comprehensive validation tests were performed for one linac following MPPG‐5.a and TG‐119 guidelines, and spot checks for the other three. Our TPS modeling/validation method was evaluated by re‐analyzing the previous 103 patient‐specific IMRT/volumetric modulated arc therapy (VMAT) QA measurements with the calculated planar doses by the single model in comparison with the analysis results using four individual Pinnacle TPS models. Results For all energies, our single model PDDs were within 1% agreement of the four‐linac commissioning measurements. The MPPG‐5.a validation tests from 5.1 through 7.5 and all TG‐119 measurements passed within the recommended tolerance limits. The IMRT QA results (mean ± standard deviation) for RayStation single model versus Pinnacle individual models were 98.9% ± 1.3% and 98.0% ± 1.4% for 6‐MV, 99.9% ± 0.1% and 99.1% ± 1.9% for 10‐MV, and 98.2% ± 1.3% and 97.9% ± 1.8% for 6‐MV‐FFF, respectively. Conclusion We successfully built and validated a single photon beam model in RayStation for four Elekta Linacs. The proposed new validation methods were proven to be both efficient and effective.

Background and purpose. Chimeric antigen receptor (CAR) T cells have been relatively ineffective against solid tumors. Low-dose radiation which can be delivered to multiple sites of metastases by targeted radionuclide therapy (TRT) can elicit immunostimulatory effects. However, TRT has never been combined with CAR T cells against solid tumors in a clinical setting. This study investigated the effects of radiation delivered by Lutetium-177 (177Lu) and Actinium-225 (225Ac) on the viability and effector function of CAR T cells in vitro to evaluate the feasibility of such therapeutic combinations. After the irradiation of anti-GD2 CAR T cells with various doses of radiation delivered by 177Lu or 225Ac, their viability and cytotoxic activity against GD2-expressing human CHLA-20 neuroblastoma and melanoma M21 cells were determined by flow cytometry. The expression of the exhaustion marker PD-1, activation marker CD69 and the activating receptor NKG2D was measured on the irradiated anti-GD2 CAR T cells. Both 177Lu and 225Ac displayed a dose-dependent toxicity on anti-GD2 CAR T cells. However, radiation enhanced the cytotoxic activity of these CAR T cells against CHLA-20 and M21 irrespective of the dose tested and the type of radionuclide. No significant changes in the expression of PD-1, CD69 and NKG2D was noted on the CAR T cells following irradiation. Given a lower CAR T cell viability at equal doses and an enhancement of cytotoxic activity irrespective of the radionuclide type, 177Lu-based TRT may be preferred over 225Ac-based TRT when evaluating a potential synergism between these therapies in vivo against solid tumors.

We analyzed the sedimentological characteristics and magnetic properties of cores from the three basins of Clear Lake, California, USA, to assess the depositional response to a series of land use changes that occurred in the watershed over the 20th century. Results indicate that distinct and abrupt shifts in particle size, magnetic concentration/mineralogy, and redox conditions occur concurrently with a variety of ecological and chemical changes in lake bed sediments. This coincidence of events occurred around 1927, a datum determined by an abrupt increase in total mercury (Hg) in Clear Lake cores and the known initiation of open‐pit Hg mining at the Sulphur Bank Mercury Mine, confirmed by ²¹⁰Pb dating. Ages below the 1927 horizon were determined by accelerator mass spectrometry on ¹⁴C of coarse organic debris. Calculated sedimentation rates below the 1927 datum are ∼1 mm/yr, whereas rates from 1927 to 2000 are up to an order of magnitude higher, with averages of ∼3.5–19 mm/yr. In both the Oaks and Upper Arms, the post‐1927 co‐occurrence of abrupt shifts in magnetic signatures with color differences indicative of changing redox conditions is interpreted to reflect a more oxygenated diagenetic regime and rapid burial of sediment below the depth of sulfate diffusion. Post‐1927 in the Oaks Arm, grain size exhibits a gradual coarsening‐upward pattern that we attribute to the input of mechanically deposited waste rock related to open‐pit mining activities at the mine. In contrast, grain size in the Upper Arm exhibits a gradational fining‐upward after 1927 that we interpret as human‐induced erosion of fine‐grained soils and chemically weathered rocks of the Franciscan Assemblage by heavy earthmoving equipment associated with a road‐ and home‐building boom, exacerbated by stream channel mining and wetlands destruction. The flux of fine‐grained sediment into the Upper Arm increased the nutrient load to the lake, and that in turn catalyzed profuse cyanobacterial blooms through the 20th century. The resulting organic biomass, in combination with the increased inorganic sediment supply, contributed to the abrupt increase in sedimentation rate after 1927.

Considerable ecological research on mercury (Hg) has focused on higher trophic level species (e.g., fishes and birds), but less on lower trophic species. Clear Lake, site of the abandoned Sulphur Bank Mercury Mine, provides a unique opportunity to study a system influenced by mine-derived Hg. An exponentially decreasing gradient of total Hg (TotHg) away from the mine allowed us to evaluate Hg bioaccumulation in planktonic and benthic invertebrates and evaluate population- and community-level parameters that might be influenced by Hg. Studies from 1992—1998 demonstrated that TotHg in lower trophic species typically decreased exponentially away from the mine, similar to trends observed in water and sediments. However, a significant amount of invertebrate TotHg (~60% for sediment-dwelling chironomid insect larvae) likely derives from Hg-laden particles in their guts. Spatially, whole-body methylmercury (MeHg) did not typically exhibit a significant decrease with increasing distance from the mine. Temporally, TotHg concentrations in plankton and chironomids did not exhibit any short-term (seasonal or annual) or long-term (multiyear) trends. Methylmercury, however, was elevated during late summer/fall in both plankton and chironomids, but it exhibited no long-term increase or decrease during this study. Although data from a 50-yr monitoring program for benthic chaoborid and chironomid larvae documented significant population fluctuations, they did not demonstrate population-level trends with respect to Hg concentrations. Littoral invertebrates also exhibited no detectable population- or community-level trends associated with the steep Hg gradient. Although sediment TotHg concentrations (1—1200 mg/kg dry mass) exceed sediment quality guidelines by up to 7000 times, it is notable that no population- or community-level effects were detected for benthic and planktonic taxa. In comparison with other sites worldwide, Clear Lake's lower trophic species typically have significantly higher TotHg concentrations, but comparable or lower MeHg concentrations, which may be responsible for the discrepancy between highly elevated TotHg concentrations and the general lack of observed population- or community-level effects. These data suggest that MeHg, as well as TotHg, should be used when establishing sediment quality guidelines. In addition, site-specific criteria should be established using the observed relationship between MeHg and observed ecological responses.

Clear Lake, California, USA, receives acid mine drainage and mercury (Hg) from the Sulphur Bank Mercury Mine, a U.S. Environmental Protection Agency (U.S. EPA) Superfund Site that was active intermittently from 1873 to 1957 and partially remediated in 1992. Mercury concentrations were analyzed primarily in four species of Clear Lake fishes: inland silversides (Menidia beryllina, planktivore), common carp (Cyprinus carpio, benthic scavenger/omnivore), channel catfish (Ictalurus punctatus, benthic omnivorous predator), and largemouth bass (Micropterus salmoides, piscivorous top predator). These data represent one of the largest fish Hg data sets for a single site, especially in California. Spatially, total Hg (TotHg) in silversides and bass declined with distance from the mine, indicating that the mine site represents a point source for Hg loading to Clear Lake. Temporally, fish Hg has not declined significantly over 12 years since mine site remediation. Mercury concentrations were variable throughout the study period, with no monotonic trends of increase or decrease, except those correlated with boom and bust cycles of an introduced fish, threadfin shad (Dorosoma petenense). However, stochastic events such as storms also influence juvenile largemouth bass Hg as evidenced during an acid mine drainage overflow event in 1995. Compared to other sites regionally and nationally, most fish in Clear Lake exhibit Hg concentrations similar to other Hg-contaminated sites, up to ~2.0 mg/kg wet mass (WM) TotHg in largemouth bass. However, even these elevated concentrations are less than would be anticipated from such high inorganic Hg loading to the lake. Mercury in some Clear Lake largemouth bass exceeded all human health fish consumption guidelines established over the past 25 years by the U.S. Food and Drug Administration (1.0 mg/kg WM), the National Academy of Sciences (0.5 mg/kg WM), and the U.S. EPA (0.3 mg/kg WM). Mercury in higher trophic level fishes exceeds ecotoxicological risk assessment estimates for concentrations that would be safe for wildlife, specifically the nonlisted Common Merganser and the recently delisted Bald Eagle. Fish populations of 11 out of 18 species surveyed exhibited a significant decrease in abundance with increasing proximity to the mine; this decrease is correlated with increasing water and sediment Hg. These trends may be related to Hg or other lake-wide gradients such as distribution of submerged aquatic vegetation.

The Sulphur Bank Mercury Mine (SBMM), active intermittently from 1873-1957 and now a USEPA Superfund site, was previously estimated to have contributed at least 100 metric tons (10⁵ kg) of mercury (Hg) into the Clear Lake aquatic ecosystem. We have confirmed this minimum estimate. To better quantify the contribution of the mine in relation to other sources of Hg loading into Clear Lake and provide data that might help reduce that loading, we analyzed Inputs and Outputs of Hg to Clear Lake and Storage of Hg in lakebed sediments using a mass balance approach. We evaluated Inputs from (1) wet and dry atmospheric deposition from both global/regional and local sources, (2) watershed tributaries, (3) groundwater inflows, (4) lakebed springs and (5) the mine. Outputs were quantified from (1) efflux (volatilization) of Hg from the lake surface to the atmosphere, (2) municipal and agricultural water diversions, (3) losses from out-flowing drainage of Cache Creek that feeds into the California Central Valley and (4) biotic Hg removal by humans and wildlife. Storage estimates include (1) sediment burial from historic and prehistoric periods (over the past 150-3,000 years) from sediment cores to ca. 2.5m depth dated using dichloro diphenyl dichloroethane (DDD), ²¹⁰Pb and ¹⁴C and (2) recent Hg deposition in surficial sediments. Surficial sediments collected in October 2003 (11 years after mine site remediation) indicate no reduction (but a possible increase) in sediment Hg concentrations over that time and suggest that remediation has not significantly reduced overall Hg loading to the lake. Currently, the mine is believed to contribute ca. 322-331 kg of Hg annually to Clear Lake, which represents ca. 86-99% of the total Hg loading to the lake. We estimate that natural sedimentation would cover the existing contaminated sediments within ca. 150-300 years.