Cd and Zn Concentrations in Soil and Silage Maize following the Addition of P Fertilizer

Studies of soil Cd and Zn are often performed on sites that are contaminated or have deficient Zn conditions. Soil characteristics and crop management could impact the soil mobility and uptake of Cd and Zn, even when considering unpolluted Cd soils and adequate soil Zn levels. The concentrations of these two metals were assessed in soil and silage maize under five P fertilization treatments at two growth stages under low Cd and sufficient Zn conditions. Pearson correlation coefficients and stepwise linear regressions were calculated to investigate the soil characteristics influencing the bioavailable metal fraction in soil and the metal concentration in silage maize. P treatments did not impact Cd accumulation in maize; however, the Zn uptake was affected by P placement at the leaf development stage. From early development to maturity, the Cd level in maize decreased to 10% of the initial uptake, while the Zn level decreased to 50% of the initial uptake. This reduction in both metals may be attributed to a dilution effect derived from high biomass production. Silage maize could alleviate the initial Cd uptake while diminishing the depressant effect of P fertilizer on Zn concentration. Further research is required to understand the effect of P fertilizer on Cd uptake and its relation to Zn under field conditions at early and mature stages.

Characterization and Mitigation of Model Bias in Parametric Mapping of Dopamine Response to Behavioral Challenge

Compartmental modeling of 11C-raclopride (RAC) is commonly used to measure dopamine response to intra-scan behavioral tasks. Bias in estimates of binding potential (BPND) and its dynamic changes (ΔBPND) can arise when the selected compartmental model deviates from the underlying biology. In this work, we characterize the bias associated with assuming a single target compartment and propose a model for reducing this bias by selectively discounting the contribution of the initial uptake period. Methods: 69 healthy young adult participants were scanned using RAC PET/MR while simultaneously performing a rewarded behavioral task. BPND and ΔBPND were estimated using an extension of the Multilinear Reference Tissue Model (MRTM2) with the task challenge encoded as a Heaviside step function. Bias was estimated using simulations designed to match the acquired data and was reduced by introducing a new model (DE-MRTM2) that reduces the biasing influence of the initial uptake period in the modeled estimation of BPND for both simulations and participant data. Results: Bias in ΔBPND was observed to vary both spatially with BPND and with the assumed value of k4. At the most likely value of k4 (0.13 min-1), the average bias and the maximum voxel bias magnitude in the nucleus accumbens were estimated to be 1.2% and 3.9% respectively. Simulations estimated that debiasing the contribution of the first 27 minutes of acquired data reduced average bias and maximum voxel bias in the nucleus accumbens ΔBPND to -0.3% and 2.4% respectively. In the acquired participant data, DE-MRTM2 produced modest changes in the experimental estimates of striatal ΔBPND, while extrastriatal bias patterns were greatly reduced. DE-MRTM2 also considerably reduced the dependence of ΔBPND upon the first-pass selection of k2'. Conclusion: Selectively discounting the contribution of the initial uptake period can help mitigate BPND- and k4-dependent bias in single compartment models of ΔBPND, while also reducing the dependence of ΔBPND on the first-pass estimation of k2'.

Cell-to-Medium Concentration Ratio Overshoot in the Uptake of Statins by Human Hepatocytes in Suspension, but Not in Monolayer: Kinetic Analysis Suggesting a Partial Loss of Functional OATP1Bs

Suspended human hepatocytes (SHH) have long been used in assessing hepatic drug uptake, while plated human hepatocytes in short-term monolayer culture (PHH) have gained use in recent years. This study aimed to cross-evaluate SHH and PHH in measuring the hepatic uptake mediated by organic anion transporting polypeptide 1Bs (OATP1Bs). We compared the time courses of cell-to-medium (C/M) concentration ratios and initial uptake clearance values of the OATP1B substrates (pitavastatin, rosuvastatin, cerivastatin, pravastatin, dehydropravastatin, and SC-62807) between SHH and PHH. For all compounds except cerivastatin, the C/M ratios in SHH displayed an apparent overshoot (an initial increase followed by a decrease) during the 180-min uptake experiment, but not in PHH. Based on the literature evidence suggesting the possible internalization of OATP1Bs in primary hepatocytes, separate experiments measured the drug uptake after varying lengths of pre-incubation in the drug-free medium. The initial uptake clearances of pitavastatin and rosuvastatin declined in SHH beyond an apparent threshold time of 20-min drug-free pre-incubation, but not in PHH. Kinetic modeling quantitatively captured the decline in the active uptake clearance in SHH, and more than half of the active uptake clearances of pitavastatin and rosuvastatin were prone to loss during the 180-min uptake experiment. These results suggested a partial, time-delayed loss of the functional OATP1Bs in SHH upon prolonged incubation. Our results indicate that PHH is more appropriate for experiments where a prolonged incubation is required, such as estimation of unbound hepatocyte-to-medium concentration ratio (Kp,uu) at the steady-state.

Uptake of pre-symptomatic testing for BRCA1 and BRCA2 is age, gender, offspring and time-dependent

BackgroundGenetic testing for BRCA1 and BRCA2 pathogenic variants (PVs) has been available in North West England since 1995. We assessed uptake of pre-symptomatic testing in 1564 families with PVs over a 24.5year follow-up (FU) period.MethodsFirst-degree relatives (FDRs) in families with BRCA1 or BRCA2 PVs were eligible from date of index family report if unaffected by a relevant cancer and alive at report date. FDRs were censored as not having undergone a pre-symptomatic test at diagnosis of a relevant cancer, date of death, age 93 or 30/03/2019. Time to uptake of pre-symptomatic testing was assessed by Kaplan–Meier curves, by gender and children.Results2554 male and 3115 female FDRs were eligible. Overall uptake was 775 (30.3%) in men and 1935 (62.1%) in women. This increased at 15 years to 33.6% and 67.9%, and continued to rise until 24 years (p<0.001). For women, the 29-year to 39-year age group had the highest uptake at 10 years FU (72.5%; p<0.01), whereas the 50-year to 59-year age group was highest in men (37.2%; p<0.01). Women <18 years at the time of familial variant identification had lower initial uptake, but this rose to >80% by 15 years. Uptake was higher in parous women (p<0.001) and in men with daughters (p<0.0001).ConclusionUptake of BRCA1/2 pre-symptomatic testing is age, gender and time-dependent, and higher in women with children and men with daughters.

Facile Synthesis and Reuse of Magnetic Black Carbon Magnetite (BC-Mag) for Fast Carbamazepine Removal from Water

Magnetic carbonaceous nanomaterials are needed in water treatment applications because they can offer both carbon surfaces for sorption of organic pollutants and ease of material magnetic retrieval for regeneration and reuse. In this study, we employed a facile one-step method to synthesize a black carbon-magnetite composite (BC-Mag) by high-temperature annealing of black carbon and hematite. The nanocomposite was easily dispersed and stable in water owing to the presence of negatively charged oxygen surface functional groups. Sorption kinetics with dissolved carbamazepine showed a rapid initial uptake with equilibrium achieved within only minutes. The sorption extent can be described with the Freundlich model, and surface area normalized sorption affinity was an order of magnitude greater than conventional granular activated carbon. The sorption extent of neutral carbamazepine remained constant between pH 2–10 while surface zeta potential decreased. BC-Mag can be reused for the sorption of carbamazepine up to six times without significant loss of the sorption extent.

Feasibility of Electronic Monitoring of Daily Oral Medications in Adolescents with Sickle Cell Disease

Background: The field has made significant strides in understanding the mechanisms underlying pediatric sickle cell disease (SCD), and the coming years will likely see the approval of several new medications to treat SCD. The impact of these medications on clinical outcomes, however, will be dependent on patient adherence. Adolescents with SCD are at particular risk for non-adherence, and as disease management increasingly includes self-administration of oral medications, adherence assessment will become a critical component of research on medication effectiveness and clinical care. While electronic monitoring devices (bottles with computer chips that record date- and time-stamps of device openings) such as MEMS® bottles are considered the "gold standard" for adherence assessment in other populations, their feasibility among adolescents with SCD remains unknown. Objectives: The primary aims of this study were to examine data on MEMS® bottle use among adolescents (ages 13-21 years) with SCD to: 1) evaluate the feasibility of MEMS® bottle use; and 2) elicit barriers and facilitators to MEMS® bottle use. Methods: As part of a larger study of a self-management intervention, adolescents were asked to use a MEMS® bottle to store and administer their daily oral medication (hydroxyurea or deferasirox) for the 18-week study duration. The larger study included baseline, post-treatment, and follow-up assessments, at which adolescents were asked to provide their MEMS® bottle for data download. Descriptive statistics were calculated to assess multiple domains of MEMS® bottle feasibility including: initial uptake (% enrolled), MEMS® initiation (% initiated), and MEMS® sustained use (% completed; % provided bottles for download ±2 weeks of scheduled study visit = "on time"). Barriers and facilitators to MEMS® use were elicited via adolescent self-report. Results: In the larger study, 18 non-Hispanic African-American adolescents (M = 17.8 years, SD = 2.6; 61% male) with HbSS were asked to use a MEMS® bottle to store their hydroxyurea (n = 14) or deferasirox (n = 4). Initial uptake was 94.7%, with 18 of 19 eligible adolescents enrolling in the study. Of the 18 enrolled adolescents, all initiated MEMS® use (100%) and 11 sustained MEMS® use through the final study endpoint (61.1%). Eight (44.4%) and 2 (11.1%) adolescents provided their MEMS® bottle for download "on time" at post-treatment (42 days) and follow-up (126 days), respectively. Barriers to MEMS® use included medication changes (i.e., medication holds, dose timing changes) and transitioning from pediatric to adult care. Facilitators included tip sheets (e.g., places to store bottle, reminder to place refills in bottle) and reminder calls. Participants took a median of 26.2% of doses using the MEMS® across the 126 days (SD = 22.4; range 0.79% - 79.3%), illustrating that electronic monitoring devices are not a solution to medication adherence, but are one component of an adherence support strategy. See Figure 1 for adherence rates over time. Discussion: Data suggest that MEMS® are acceptable to adolescents with SCD. Ensuring sustained MEMS® use, however, will likely require additional supports. For example, electronic monitors which automatically transmit data in real-time via Bluetooth or cellular connections would eliminate the need for adolescents to bring bottles to study visits for data downloads. Researchers and clinicians interested in using electronic monitoring devices are encouraged to consider remote monitoring capabilities along with other device features when selecting a product. Larger studies are needed to evaluate concordance between rates of adherence obtained via electronic monitoring and other assessments and to validate electronically-monitored medication adherence with clinically-relevant outcomes for adolescents with SCD. Figure 1 Disclosures Quinn: Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Research Support.