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Tests on N-Viro Soil, produced at a facility in Toledo, OH, revealed inhibition of seed germination, and efforts to take away the soluble salts from the material showed little improvement and no changes in the germination process. However, tests on the soil, after it had aged for at least a year, indicated no such germination inhibition. Seven-month-old material also showed excellent germination, with no major difference in germination when compared with sand.

The influence of dexrazoxane on doxorubicin pharmacokinetics was investigated in four dogs using the two treatment sequences of saline/doxorubicin or dexrazoxane/doxorubicin. Intravenous doses of 1.5 mg/kg doxorubicin and 30 mg/kg (the 20-fold multiple) dexrazoxane were given separately, with doxorubicin being injected within 1 min of the dexrazoxane dose. Both doxorubicin and its 13-dihydro metabolite doxorubicinol were quantified in plasma and urine using a validated high-performance liquid chromatographic (HPLC) fluorescence assay. The doxorubicin plasma concentration versus time data were adequately fit by a three-compartment model. The mean half-lives calculated for the fast and slow distributive and terminal elimination phases in the saline/doxorubicin group were 3.0 +/- 0.5 and 32.2 +/- 12.8 min and 30.0 +/- 4.0 h, respectively. The model-predicted plasma concentrations were virtually identical for the saline and dexrazoxane treatment groups. Analysis of variance of the area under the plasma concentration-time curve (AUCo-infinity), terminal elimination rate (lambda z), systemic clearance (CLs), and renal clearance (CLr) for the parent drug showed no statistically significant difference (P greater than 0.05) between the two treatments. Furthermore, the doxorubicinol plasma AUCo-t value and the doxorubicinol-to-doxorubicin AUCo-t ratio showed no significant difference, demonstrating that dexrazoxane had no effect on the metabolic capacity for formation of the 13-dihydro metabolite. The total urinary excretion measured as parent drug plus doxorubicinol and the metabolite-to-parent ratio in urine were also unaffected by the presence of dexrazoxane. The myelosuppressive effects of doxorubicin as determined by WBC monitoring revealed no apparent difference between the two treatments. In conclusion, these results show that drug exposure was similar for the two treatment arms. No kinetic interaction with dexrazoxane suggests that its coadministration is unlikely to modify the safety and/or efficacy of doxorubicin. [ABSTRACT FROM AUTHOR]

Diversifying science, technology, engineering, and mathematics (STEM) requires a critical examination of institutional structures at every educational level. In higher education, performance in core introductory courses required for STEM degrees is strongly associated with degree completion. Leveraging a multi-institutional database, we examine nearly 110,000 student records from six large, public, research-intensive universities in order to assess whether these introductory courses disproportionately weed out underrepresented minority (URM) students. We find that the association between low performance in an introductory STEM class and failure to obtain a STEM degree is stronger for URM students than for other students, even after controlling for academic preparation in high school and intent to obtain a STEM degree. To facilitate interpretation of our multivariate logistic regression model, and to highlight the dire situation in higher education, we also calculate predicted probabilities of STEM degree attainment for students of various demographics. The probability of obtaining a STEM degree for a STEM-intending white male student with average academic preparation who receives grades of C or better in all introductory courses is 48%. In contrast, for an otherwise similar URM female student, the probability is merely 35%. If these students receive less than a C in even one introductory STEM course, the probabilities drop to 33% and 21%, respectively., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

We report electronic medical record interventions to reduce Clostridioides difficile testing risk 'alert fatigue.' We used a behavioral approach to diagnostic stewardship and observed a decrease in the number of tests ordered of ~4.5 per month (P < .0001). Although the number of inappropriate tests decreased during the study period, delayed testing increased.

Purpose: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC)., Materials and Methods: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test., Results: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS., Conclusions: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to consolidate epidemiological evidence for the association between dietary supplements of vitamins and minerals and thyroid cancer development, as well as to contribute to evidence-based dietary recommendations for thyroid cancer primary prevention. We carried out a systematic literature review specifically for dietary supplement and thyroid cancer risk. MEDLINE, EMBASE, and Dissertations and Theses were systematically searched to identify original epidemiological studies with a comparison group that investigated vitamin or mineral supplementation as an etiological factor for thyroid cancer. In total, 11 independent studies were identified and reviewed. Our qualitative summary showed conflicting results for common antioxidants including vitamins A, C, and E and β-carotene in relation to thyroid cancer. Similarly, results for dietary supplement combinations as well as other individual vitamins and minerals (vitamin B complex, vitamin D, iodine, calcium, zinc, magnesium, and iron) are largely inconsistent across studies. Overall, our review suggested that the current evidence to support any protective or hazardous effect of vitamin or mineral supplements on thyroid cancer development is inconclusive and additional studies addressing previous limitations are necessary to elucidate this possible association. In particular, reverse causality is of major concern and should be addressed by prospective studies with large and representative samples.

A randomized, four-way cross-over design was used to assess the disposition of the cardioprotective agent, dexrazoxane, in four male beagle dogs following single I.V. administration of 10, 25, 50, and 100 mg kg-1 doses. Parent drug was quantified in plasma and urine with a validated high-pressure liquid chromatographic-electrochemical assay. A two-compartment open model adequately described the dexrazoxane plasma concentration versus time data. The terminal half-life ranged between 1.1 and 1.3 h and the apparent steady-state distribution volume was 0.67 L kg-1. The systemic clearance (CL) ranged from 10.3 to 11.5 mL min-1 kg-1, while estimates of renal clearance approximated the glomerular filtration rate (GFR approximately 3.2-4.9 mL min-1 kg-1). Over the dose range evaluated, CL was dose independent (ANOVA, p = 0.33), while concentration at the end of infusion (Cend) and the area under the concentration versus time curve (AUC) were directly proportional to the dose (r > 0.999). The blood cell to plasma partitioning ratio was approximately 0.517 and drug was essentially unbound to plasma proteins (fu approximately 0.95). Dexrazoxane appeared to be subject to low organ extraction, since the hepatic and renal drug extraction ratios were on the order of 0.228 +/- 0.054 and 0.184 +/- 0.024, respectively. These results suggest a relatively small drug distribution space (approximately equal to total-body water) and low tissue and plasma protein binding. In light of the low plasma protein binding and extraction ratio exhibited by dexrazoxane, metabolic capacity and renal function would appear to be the predominant variables affecting the CL of this drug. The constancy of the half-life, CL, and VSS with increasing dose indicates dose-independent disposition for dexrazoxane. Thus a linear increase in the systemic exposure can be predicted over this dose range.

A 100- to 3200-mg dose range of FCE 22,178 was studied in this phase I single-dose escalation safety/kinetics study. After oral administration, a rapid drug absorptive phase and a biexponential disposition profile were observed. Mean estimates of the terminal elimination half-life of FCE 22,178, over the doses studied, ranged from 7.6 to 14.4 hours. A disproportionate increase in both maximum peak plasma concentration (Cmax) and area under the curve (AUC0-infinity) was noticed for doses higher than 400 mg. Mean estimates of systemic clearance (CLs/F) over the 100- to 400-mg doses were 0.053 to 0.064 L/hour/kg, and were significantly higher for the three higher dose levels. This nonlinearity appears to be related to the changes in oral bioavailability. Estimates of distribution volume (Vd, lambda z/F) for FCE 22,178 increased from 0.75 L/kg at the 100-mg dose to 3.00 L/kg at the 3200-mg dose, and renal clearance (CLr) also increased with dose. Both observations may be related to an increase in free fraction of FCE 22,178 at higher doses. Urinary excretion of unchanged drug averaged < 10% for all dose levels. The urinary excretion of the glucuronide metabolite (M1) averaged 41 to 70% for doses up to 400 mg, but diminished to 13% at the 3200-mg dose. The disposition of M1 appeared to be formation-rate limited. In addition, the ratio of the formation to the disposition clearance for M1 was relatively stable and apparently dose independent. No drug-related adverse experiences were observed over the studied dose range after single doses at FCE 22,178.

Sensitive HPLC-UV methodology has been developed and validated for quantitating rifabutin, an antimycobacterial, and its 25-desacetyl metabolite, LM-565, in human plasma and urine. The HPLC separation for both plasma and urine samples was performed on an ODS, 5-microns, reverse-phase column (25 cm x 4.6-cm ID) using a mobile phase of acetonitrile/0.05 M potassium phosphate, pH 4.2, with triethylamine, (38:61.5:0.5, v/v), at a flow rate of 1.0 ml/min. The separation eluate was monitored by absorbance at 275 nm. Plasma samples (1 ml) were spiked with an internal standard (medazepam), buffered at pH 7.4 and extracted with 80:20 (v/v) hexane:ethyl acetate, and then back extracted with acidified water (0.05 M H3PO4). Linearity was established between 5.0-800 and 2.5-400 ng/ml for rifabutin and LM-565, respectively. Intraday imprecision for rifabutin and LM-565 plasma quality controls prepared at 7.3 and 3.2 ng/ml, respectively, was less than 15% relative standard deviation (RSD). Absolute recovery for parent drug and metabolite, from plasma, was greater than 90% throughout the respective dynamic ranges and greater than 70% for medazepam. Urine samples (1 ml) were acidified with 50 microliters of 3.6 M H2SO4 and diluted with 0.1 M ammonium acetate. Linearity was established between 100 and 5000 ng/ml for both rifabutin and LM-565. Intraday imprecision for a urine control at 200 ng/ml was less than or equal to 12% RSD for either component. The method is currently being used to support Phase I kinetics program for rifabutin in prophylaxis of MAC infection of AIDS patients. Application of this method to a bioavailability assessment is presented.