Development of a Greenhouse Assay to Screen Soybean Varieties for Resistance to Aerial Blight Caused by Rhizoctonia solani Anastomosis Group 1-IA.

Aerial blight, caused by the fungus Rhizoctonia solani anastomosis group (AG) 1-IA, is an economically important soybean disease in the mid-Southern United States. Management has relied on fungicide applications during the season, but there is an increasing prevalence of resistance to commonly used strobilurin fungicides and an urgent need to identify soybean varieties resistant to aerial blight. Because the patchy distribution of the pathogen complicates field variety screening, the present study aimed to develop a greenhouse screening protocol to identify soybean varieties resistant to aerial blight. For this, 88 pathogen isolates were collected from commercial fields and research farms across five Louisiana parishes, and 77% were confirmed to be R. solani AG1-IA. Three polymorphic codominant microsatellite markers were used to explore the genetic diversity of 43 R. solani AG1-IA isolates, which showed high genetic diversity, with 35 haplotypes in total and only two haplotypes common to two other locations. Six genetically diverse isolates were chosen and characterized for their virulence and fungicide sensitivity. The isolate AC2 was identified as the most virulent and was resistant to both active ingredients, azoxystrobin and pyraclostrobin, tested. The six isolates were used in greenhouse variety screening trials using a millet inoculation protocol. Of the 31 varieties screened, only Armor 48-D25 was classified as moderately resistant, and plant height to the first node influenced final disease severity. The study provides short-term solutions for growers to choose less susceptible varieties for planting and lays the foundation to characterize host resistance against this important soybean pathogen.

Characterization of QoI-Fungicide Resistance in Cercospora Isolates Associated with Cercospora Leaf Blight of Soybean from the Southern United States.

Cercospora leaf blight (CLB) of soybean, caused by Cercospora cf. flagellaris, C. kikuchii, and C. cf. sigesbeckiae, is an economically important disease in the southern United States. Cultivar resistance to CLB is inconsistent; therefore, fungicides in the quinone outside inhibitor (QoI) class have been relied on to manage the disease. Approximately 620 isolates from plants exhibiting CLB were collected between 2018 and 2021 from 19 locations in eight southern states. A novel polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay based on two genes, calmodulin and histone h3, was developed to differentiate between the dominant species of Cercospora, C. cf. flagellaris, and C. cf. sigesbeckiae. A multilocus phylogenetic analysis of actin, calmodulin, histone h3, ITS rDNA, and transcription elongation factor 1-α was used to confirm PCR-RFLP results and identify remaining isolates. Approximately 80% of the isolates collected were identified as C. cf. flagellaris, while 15% classified as C. cf. sigesbeckiae, 2% as C. kikuchii, and 3% as previously unreported Cercospora species associated with CLB in the United States. PCR-RFLP of cytochrome b (cytb) identified QoI-resistance conferred by the G143A substitution. Approximately 64 to 83% of isolates were determined to be QoI-resistant, and all contained the G143A substitution. Results of discriminatory dose assays using azoxystrobin (1 ppm) were 100% consistent with PCR-RFLP results. To our knowledge, this constitutes the first report of QoI resistance in CLB pathogen populations from Alabama, Arkansas, Kentucky, Mississippi, Missouri, Tennessee, and Texas. In areas where high frequencies of resistance have been identified, QoI fungicides should be avoided, and fungicide products with alternative modes-of-action should be utilized in the absence of CLB-resistant soybean cultivars.

The utility of H2 receptor antagonists in preventing infusion-related reactions to paclitaxel chemotherapy.

BACKGROUND: Paclitaxel has a risk of infusion-related reactions (IRRs) and despite no prospective evidence, is often given with premedication including a corticosteroid, H1 antagonist, and H2 antagonist (H2RA). Backorders impacted the supply of intravenous H2RAs at our center, and it was removed as routine premedication. The authors compared the incidence of IRR in patients treated without H2RA to patients receiving standard H2RA premedication. METHODS: The authors reviewed outpatients starting paclitaxel at the Ottawa Hospital from December 2019 to October 2021. Two cohorts were created: patients treated without H2RA premedication (intervention), and those receiving standard H2RA (control). Demographics, treatment, and IRR information were collected retrospectively. Primary end point was rate of grade ≥2 IRRs during first two doses of paclitaxel. RESULTS: A total of 182 patients were treated without H2RA premedication, compared to 184 control patients treated during non-backorder periods. Baseline characteristics included: median age, 63 years; 86% female; and primary tumor 52% breast/24% gynecologic/10% gastric/esophageal/8% lung/6% other. There were no significant differences between cohorts in baseline characteristics. There was no difference in the rate of grade ≥2 IRR between cohorts; 12.1% (22 of 182; 95% confidence interval [CI], 7.7%-17.7%) for patients treated without H2RA, and 15.1% (28 of 185; 95% CI, 10.3%-21.1%) for control patients. The rate of grade ≥3 IRRs were also similar, 4.4% in intervention cohort versus 3.8% in control cohort. CONCLUSIONS: The removal of H2RAs from premedication for paclitaxel did not result in an increased incidence of IRRs. The use of H2RAs in preventing IRRs to paclitaxel should be re-evaluated.

A value of information framework for assessing the trade-offs associated with uncertainty, duration, and cost of chemical toxicity testing.

A number of investigators have explored the use of value of information (VOI) analysis to evaluate alternative information collection procedures in diverse decision-making contexts. This paper presents an analytic framework for determining the value of toxicity information used in risk-based decision making. The framework is specifically designed to explore the trade-offs between cost, timeliness, and uncertainty reduction associated with different toxicity-testing methodologies. The use of the proposed framework is demonstrated by two illustrative applications which, although based on simplified assumptions, show the insights that can be obtained through the use of VOI analysis. Specifically, these results suggest that timeliness of information collection has a significant impact on estimates of the VOI of chemical toxicity tests, even in the presence of smaller reductions in uncertainty. The framework introduces the concept of the expected value of delayed sample information, as an extension to the usual expected value of sample information, to accommodate the reductions in value resulting from delayed decision making. Our analysis also suggests that lower cost and higher throughput testing also may be beneficial in terms of public health benefits by increasing the number of substances that can be evaluated within a given budget. When the relative value is expressed in terms of return-on-investment per testing strategy, the differences can be substantial.

Meta-Analytic Modeling of the Severity-Yield Relationships in Soybean Frogeye Leaf Spot Epidemics.

Frogeye leaf spot (FLS), caused by Cercospora sojina, is an important foliar disease affecting soybean in the United States. A meta-analytic approach including 39 fungicide trials conducted from 2012 to 2021 across eight states (Alabama, Arkansas, Illinois, Iowa, Kentucky, Louisiana, Mississippi, Tennessee) was used to assess the relationship between FLS severity and soybean yield. Correlation and regression analyses were performed separately to determine Fisher's transformation of correlation coefficients (Zr), intercept (ß0) and slope (ß1). Disease pressure (low severity, ≤34.5; high severity, >34.5%) and yield class (low, ≤3,352; high, >3,352 kg/ha) were included as categorical moderators. Pearson's [Formula: see text], obtained from back-transforming the [Formula: see text]r estimated by an overall random-effects model, showed a significant negative linear relationship between FLS severity and yield ([Formula: see text] = -0.60). The [Formula: see text]r was affected by disease pressure (P = 0.0003) but not by yield class (P = 0.8141). A random-coefficient model estimated a slope of -19 kg/ha for each percent severity for a mean attainable yield of 3,719.9 kg/ha. Based on the overall mean (95% CI) of the intercept and slope estimated by the random-coefficients model, the estimated overall relative damage coefficient was 0.51% (0.36 to 0.69), indicating that a percent increase in FLS severity reduced yield by 0.51%. The best model included yield class as a covariate, and population-average intercepts differed significantly between low (3,455.1 kg/ha) and high (3,842.7 kg/ha) yield classes. This highlights the potential impact of FLS on soybean yield if not managed and may help in disease management decisions.

Efficacy and Profitability of Fungicides for Managing Frogeye Leaf Spot on Soybean in the United States: A 10-Year Quantitative Summary.

Frogeye leaf spot (FLS), caused by Cercospora sojina, is an economically important disease of soybean in the United States. Data from 66 uniform fungicide trials (UFTs) conducted from 2012 to 2021 across eight states (Alabama, Arkansas, Illinois, Iowa, Kentucky, Louisiana, Mississippi, and Tennessee) were gathered and analyzed to determine the efficacy and profitability of the following fungicides applied at the beginning pod developmental stage (R3): azoxystrobin + difenoconazole (AZOX + DIFE), difenoconazole + pydiflumetofen (DIFE + PYDI), pyraclostrobin (PYRA), pyraclostrobin + fluxapyroxad + propiconazole (PYRA + FLUX + PROP), tetraconazole (TTRA), thiophanate-methyl (TMET), thiophanate-methyl + tebuconazole (TMET + TEBU), and trifloxystrobin + prothioconazole (TFLX + PROT). A network meta-analytic model was fitted to the log of the means of FLS severity data and to the nontransformed mean yield for each treatment, including the nontreated. The percent reduction in disease severity (%) and the yield response (kg/ha) relative to the nontreated was the lowest for PYRA (11%; 136 kg/ha) and the greatest for DIFE + PYDI (57%; 441 kg/ha). A significant decline in efficacy over time was detected for PYRA (18 percentage points [p.p.]), TTRA (27 p.p.), AZOX + DIFE (18 p.p.), and TMET + TEBU (19 p.p.) by using year as a continuous covariate in the model. Finally, probabilities of breaking even were the greatest (>65%) for the most effective fungicide DIFE + PYDI and the lowest (<55%) for PYRA. Results of this meta-analysis may be useful to support decisions when planning fungicide programs.

Perceived feasibility of sward management options in permanent grassland of Alpine regions and expected effects on delivery of ecosystem services.

Agriculture in Alpine regions plays an important role for multiple ecosystem services (ES) supplied from permanent grassland (PG). This paper investigates the feasibility of sward renewal, overseeding, and rising plate meters on PG for the Swiss Alpine region and analyses their expected effects on ES supply. Sward renewal and overseeding are management options implemented in response to a decline of grassland yields and nutritive value or sward damage. Rising plate meters focus on increased grass utilisation for improving profitability of grassland farms in a sustainable manner. The aim was to improve the understanding which of these three PG management practices could be promoted to deliver a wide range of agricultural and non-agricultural ESs in the Swiss Alpine region. Through interviews with 75 farmers (including organic and intensive/extensive non-organic farmers) and a Delphi-methodology on a panel of experts (N = 10 experts with different expertise), we found that sward renewal is perceived to have negative effects on biodiversity, carbon storage, flood control, prevention of soil erosion, and prevention of loss of organic matter in Alpine regions. Therefore, sward renewal should not be promoted, although about half of the farmers interviewed had already carried out the practice on plots following severe sward damage in Alpine regions. Overseeding is perceived to have positive effects on biodiversity, prevention of soil erosion, and grass production. Thus, the high level of overseeding that is currently practiced in the Swiss Alpine region is probably sustainable. Rising plate meters do not play a significant role in PG management in the Alpine region because calibration in PG with diverse grassland botanical composition in the Alpine region is too difficult.

Negotiating mutualism: A locus for exploitation by rhizobia has a broad effect size distribution and context-dependent effects on legume hosts.

In mutualisms, variation at genes determining partner fitness provides the raw material upon which coevolutionary selection acts, setting the dynamics and pace of coevolution. However, we know little about variation in the effects of genes that underlie symbiotic fitness in natural mutualist populations. In some species of legumes that form root nodule symbioses with nitrogen-fixing rhizobial bacteria, hosts secrete nodule-specific cysteine-rich (NCR) peptides that cause rhizobia to differentiate in the nodule environment. However, rhizobia can cleave NCR peptides through the expression of genes like the plasmid-borne Host range restriction peptidase (hrrP), whose product degrades specific NCR peptides. Although hrrP activity can confer host exploitation by depressing host fitness and enhancing symbiont fitness, the effects of hrrP on symbiosis phenotypes depend strongly on the genotypes of the interacting partners. However, the effects of hrrP have yet to be characterised in a natural population context, so its contribution to variation in wild mutualist populations is unknown. To understand the distribution of effects of hrrP in wild rhizobia, we measured mutualism phenotypes conferred by hrrP in 12 wild Ensifer medicae strains. To evaluate context dependency of hrrP effects, we compared hrrP effects across two Medicago polymorpha host genotypes and across two experimental years for five E. medicae strains. We show for the first time in a natural population context that hrrP has a wide distribution of effect sizes for many mutualism traits, ranging from strongly positive to strongly negative. Furthermore, we show that hrrP effect size varies across host genotypes and experiment years, suggesting that researchers should be cautious about extrapolating the role of genes in natural populations from controlled laboratory studies of single genetic variants.

A Framework that Considers the Impacts of Time, Cost, and Uncertainty in the Determination of the Cost Effectiveness of Toxicity-Testing Methodologies.

Regulatory agencies are required to evaluate the impacts of thousands of chemicals. Toxicological tests currently used in such evaluations are time-consuming and resource intensive; however, advances in toxicology and related fields are providing new testing methodologies that reduce the cost and time required for testing. The selection of a preferred methodology is challenging because the new methodologies vary in duration and cost, and the data they generate vary in the level of uncertainty. This article presents a framework for performing cost-effectiveness analyses (CEAs) of toxicity tests that account for cost, duration, and uncertainty. This is achieved by using an output metric-the cost per correct regulatory decision-that reflects the three elements. The framework is demonstrated in two example CEAs, one for a simple decision of risk acceptability and a second, more complex decision, involving the selection of regulatory actions. Each example CEA evaluates five hypothetical toxicity-testing methodologies which differ with respect to cost, time, and uncertainty. The results of the examples indicate that either a fivefold reduction in cost or duration can be a larger driver of the selection of an optimal toxicity-testing methodology than a fivefold reduction in uncertainty. Uncertainty becomes of similar importance to cost and duration when decisionmakers are required to make more complex decisions that require the determination of small differences in risk predictions. The framework presented in this article may provide a useful basis for the identification of cost-effective methods for toxicity testing of large numbers of chemicals.

Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique.

The antibiotic-resistant bacteria-associated infections are a major global healthcare threat. New classes of antimicrobial compounds are urgently needed as the frequency of infections caused by multidrug-resistant microbes continues to rise. Recent metagenomic data have demonstrated that there is still biosynthetic potential encoded in but transcriptionally silent in cultivatable bacterial genomes. However, the culture conditions required to identify and express silent biosynthetic gene clusters that yield natural products with antimicrobial activity are largely unknown. Here, we describe a new antibiotic discovery scheme, dubbed the modified crowded plate technique (mCPT), that utilizes complex microbial interactions to elicit antimicrobial production from otherwise silent biosynthetic gene clusters. Using the mCPT as part of the antibiotic crowdsourcing educational program Tiny EarthTM, we isolated over 1400 antibiotic-producing microbes, including 62 showing activity against multidrug-resistant pathogens. The natural product extracts generated from six microbial isolates showed potent activity against vancomycin-intermediate resistant Staphylococcus aureus. We utilized a targeted approach that coupled mass spectrometry data with bioactivity, yielding a new macrolactone class of metabolite, desertomycin H. In this study, we successfully demonstrate a concept that significantly increased our ability to quickly and efficiently identify microbes capable of the silent antibiotic production.

Data Mining Approaches for Assessing Chemical Coexposures Using Consumer Product Purchase Data.

The use of consumer products presents a potential for chemical exposures to humans. Toxicity testing and exposure models are routinely employed to estimate risks from their use; however, a key challenge is the sparseness of information concerning who uses products and which products are used contemporaneously. Our goal was to demonstrate a method to infer use patterns by way of purchase data. We examined purchase patterns for three types of personal care products (cosmetics, hair care, and skin care) and two household care products (household cleaners and laundry supplies) using data from 60,000 households collected over a one-year period in 2012. The market basket analysis methodology frequent itemset mining (FIM) was used to identify co-occurring sets of product purchases for all households and demographic groups based on income, education, race/ethnicity, and family composition. Our methodology captured robust co-occurrence patterns for personal and household products, globally and for different demographic groups. FIM identified cosmetic co-occurrence patterns captured in prior surveys of cosmetic use, as well as a trend of increased diversity of cosmetic purchases as children mature to teenage years. We propose that consumer product purchase data can be mined to inform person-oriented use patterns for high-throughput chemical screening applications, for aggregate and combined chemical risk evaluations.

Diaporthe Seed Decay of Soybean [Glycine max (L.) Merr.] Is Endemic in the United States, But New Fungi Are Involved.

Diaporthe seed decay can compromise seed quality in soybean [Glycine max (L.) Merr.] in the warm and humid production areas of the United States during crop maturation. In the current study, 45 isolates of Diaporthe were recovered from seed sampled from soybean fields affected by Diaporthe-associated diseases in eight U.S. states in 2017. The isolates obtained belonged to 10 species of Diaporthe based on morphology and phylogenetic analyses of the internal transcribed spacer, partial translation elongation factor 1-α, and ß-tubulin gene sequences. The associated species included D. aspalathi, D. caulivora, D. kongii, D. longicolla, D. sojae, D. ueckerae, D. unshiuensis, and three novel fungi, D. bacilloides, D. flavescens, and D. insulistroma. One isolate each of the 10 species was examined for pathogenicity on seed of cultivar Sava under controlled conditions. Seven days postinoculation, significant differences in the percentages of decayed seeds and seedling necrosis were observed among the isolates and the noninoculated control (P < 0.0001). While the isolates of D. bacilloides, D. longicolla, and D. ueckerae caused a significantly greater percentage of decayed seeds (P < 0.0001), the isolate of D. aspalathi caused the greatest seedling necrosis (P < 0.0001). The observation of new fungi causing Diaporthe seed decay suggests the need for a more comprehensive survey in U.S. soybean producing areas since members of the genus Diaporthe appear to form a complex that causes seed decay.

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer.

BACKGROUND: Small cell lung cancer (SCLC) represents approximately 15% of lung cancers, and approximately 70% are diagnosed as extensive-stage SCLC (ES-SCLC). Although ES-SCLC is highly responsive to chemotherapy, patients typically progress rapidly, and there is an urgent need for new therapies. Immune checkpoint inhibitors (ICIs) have recently been investigated in SCLC, and this review provides guidance on the use of these agents in ES-SCLC based on phase III evidence. METHODS: Published and presented literature on phase III data addressing use of ICIs in ES-SCLC was identified using the key search terms "small cell lung cancer" AND "checkpoint inhibitors" (OR respective aliases). Directed searches of eligible studies were periodically performed to ensure capture of the most recent data. RESULTS: Six phase III trials were identified, with four assessing the benefits of ICIs plus chemotherapy first-line, one evaluating ICIs as first-line therapy maintenance, and one assessing ICI monotherapy after progression on platinum-based chemotherapy. The addition of ipilimumab or tremelimumab to first-line treatment or as first-line maintenance did not improve survival. Two out of three studies combining PD-1/PD-L1 inhibitors with first-line platinum-based chemotherapy demonstrated significant long-lasting survival benefits and improved quality of life with no unexpected safety concerns. PD-1/PD-L1 inhibitors as first-line maintenance or in later lines of therapy did not improve survival. Biomarker research is ongoing as well as research into the role of ICIs in combination with radiation therapy in limited-stage SCLC. CONCLUSION: The addition of atezolizumab or durvalumab to first-line platinum-based chemotherapy for ES-SCLC prolongs survival and improves quality of life. IMPLICATIONS FOR PRACTICE: Platinum-based chemotherapy has been standard of care for extensive-stage small cell lung cancer (ES-SCLC) for more than a decade. Six recent phase III trials investigating immune checkpoint inhibitors (ICIs) have clarified the role of these agents in this setting. Although ICIs were assessed first-line, as first-line maintenance, and in later lines of therapy, the additions of atezolizumab or durvalumab to first-line platinum-based chemotherapy were the only interventions that significantly improved overall survival and increased quality of life. These combinations should therefore be considered standard therapy for first-line ES-SCLC. Biomarker research and investigations into the role of ICIs for limited-stage disease are ongoing.

Potential Life-Years Lost: The Impact of the Cancer Drug Regulatory and Funding Process in Canada.

BACKGROUND: Canada has an established publicly funded health care system with a complex drug approval and funding process. After proof of efficacy (POE; key publication/presentation) and before becoming publicly accessible, each drug undergoes a Health Canada approval process, a health technology assessment (HTA), a pricing negotiation, and finally individual provincial funding agreements. We quantified potential life-years lost during this process. METHODS: We analyzed drugs for advanced lung, breast, and colorectal cancer that underwent the HTA process between 2011 and 2016. Life-years lost were calculated by multiplying documented improvement in progression-free and overall survival, number of eligible patients, and time from POE to first public funding. For conservative calculation, we assumed all eligible patients in Canada had access at the time of first public funding, whereas in reality provinces fund at different time points. RESULTS: We analyzed 21 drugs. Of these, 15 have been funded publicly. The time from POE to first public funding ranged from 14.0 to 99.2 months (median 26.6 months). Total overall life-years lost from POE to first public funding were 39,067 (lung 32,367; breast 6,691). Progression-free life-years lost from POE to first public funding were 48,037 (lung 9,139, breast 15,827, colorectal 23,071). CONCLUSION: The number of potential life-years lost during the drug regulatory and funding process in Canada is substantial, largely driven by delays to funding of colorectal cancer drugs. Recognizing that interprovincial differences exist and that eligible patients may not all receive a given drug, if even a fraction does so, the impact of delays remains substantive. Collaborative national initiatives are required to address this major barrier to treatment access. IMPLICATIONS FOR PRACTICE: Patients may spend lengthy periods of time awaiting access to new and effective cancer drugs. Patients with private drug insurance or personal funds or who reside in certain Canadian provinces may obtain some drugs sooner than others, potentially creating a two-tiered access system. The cancer drug access and public funding system must be expedited to improve equity.

Microsymbiont discrimination mediated by a host-secreted peptide in Medicago truncatula.

The legume-rhizobial symbiosis results in the formation of root nodules that provide an ecological niche for nitrogen-fixing bacteria. However, plant-bacteria genotypic interactions can lead to wide variation in nitrogen fixation efficiency, and it is not uncommon that a bacterial strain forms functional (Fix+) nodules on one plant genotype but nonfunctional (Fix-) nodules on another. Host genetic control of this specificity is unknown. We herein report the cloning of the Medicago truncatula NFS1 gene that regulates the fixation-level incompatibility with the microsymbiont Sinorhizobium meliloti Rm41. We show that NFS1 encodes a nodule-specific cysteine-rich (NCR) peptide. In contrast to the known role of NCR peptides as effectors of endosymbionts' differentiation to nitrogen-fixing bacteroids, we demonstrate that specific NCRs control discrimination against incompatible microsymbionts. NFS1 provokes bacterial cell death and early nodule senescence in an allele-specific and rhizobial strain-specific manner, and its function is dependent on host genetic background.

Interindividual Variation in Source-Specific Doses is a Determinant of Health Impacts of Combined Chemical Exposures.

All individuals are exposed to multiple chemicals from multiple sources. These combined exposures are a concern because they may cause adverse effects that would not occur from an exposure recieved from any single source. Studies of combined chemical exposures, however, have found that the risks posed by such combined exposures are almost always driven by exposures from a few chemicals and sources and frequently by a single chemical from a single source. Here, a series of computer simulations of combined exposures are used to investigate when multiple sources of chemicals drive the largest risks in a population and when a single chemical from a single source is responsible for the largest risks. The analysis found that combined exposures drive the largest risks when the interindividual variation of source-specific doses is small, moderate-to-high correlations occur between the source-specific doses, and the number of sources affecting an individual varies across individuals. These findings can be used to identify sources with the greatest potential to cause combined exposures of concern.

Consensus Modeling of Median Chemical Intake for the U.S. Population Based on Predictions of Exposure Pathways.

Prioritizing the potential risk posed to human health by chemicals requires tools that can estimate exposure from limited information. In this study, chemical structure and physicochemical properties were used to predict the probability that a chemical might be associated with any of four exposure pathways leading from sources-consumer (near-field), dietary, far-field industrial, and far-field pesticide-to the general population. The balanced accuracies of these source-based exposure pathway models range from 73 to 81%, with the error rate for identifying positive chemicals ranging from 17 to 36%. We then used exposure pathways to organize predictions from 13 different exposure models as well as other predictors of human intake rates. We created a consensus, meta-model using the Systematic Empirical Evaluation of Models framework in which the predictors of exposure were combined by pathway and weighted according to predictive ability for chemical intake rates inferred from human biomonitoring data for 114 chemicals. The consensus model yields an R2 of ∼0.8. We extrapolate to predict relevant pathway(s), median intake rate, and credible interval for 479 926 chemicals, mostly with minimal exposure information. This approach identifies 1880 chemicals for which the median population intake rates may exceed 0.1 mg/kg bodyweight/day, while there is 95% confidence that the median intake rate is below 1 µg/kg BW/day for 474572 compounds.

A prospective intervention to improve happiness and reduce burnout in oncologists.

BACKGROUND: There is a paucity of data about effective interventions to improve happiness and reduce burnout in oncologists. Benjamin Franklin developed a 13-week program of "necessary activities" or "virtues" (temperance, silence, order, resolution, frugality, industry, sincerity, justice, moderation, cleanliness, tranquility, chastity, and humility) to follow, in his attempt at self-improvement. In this pilot study, we explored whether using a modified version of this was associated with any discernable impact on physician happiness, burnout, or compliance with each of the virtues. METHODS: Self-reported happiness (Oxford happiness scores) and burnout (Abbreviated Maslach Burnout Inventory) were completed at baseline (pre-study), week 13, and 1 month after completion of the program. Each day during the 13-week program, oncologists were emailed a list of virtues to focus on and scored how they felt they were complying with them. The oncologist's spouses also assessed how they felt the oncologist was complying with the virtues. RESULTS: Thirteen physicians completed the baseline scores, 11 completed Maslach/Oxford scores at the end of the study, and 8 the 1-month post-study assessment. No significant improvements in happiness and burnout (emotional exhaustion, depersonalization, personal accomplishment) scores were observed. Statistically significant changes in self-rated virtue scores were observed for temperance (p = 0.046), order (p = 0.049), and resolution (p = 0.014). Additionally, although not reaching statistical significance, 11 of 13 virtues (excepting sincerity and chastity) assessed by spouses indicated a positive change over time. CONCLUSION: In this hypothesis generating study, daily reflection on personal virtues was not associated with any statistically significant change in happiness or burnout scores. Alternative strategies should be considered.