Financial assistance and other financial coping strategies after a pediatric cancer diagnosis.

BACKGROUND: Families experience financial burden and household material hardship (HMH) after a pediatric cancer diagnosis. This study investigates types of financial assistance and other financial coping strategies (FCS) adopted by families during the first year after diagnosis. METHODS: Retrospective survey of caregivers of pediatric patients diagnosed with cancer from 2015 to 2019. The survey collected data on demographics, diagnosis, income, HMH, and private, hospital, and government assistance received and other FCS adopted after diagnosis. Bivariate and multivariable logistic regressions were used to analyze FCS by income. Subgroup analysis of families experiencing HMH was used to identify predictors of receiving government assistance. RESULTS: Of 156 respondents, 52% were low-to-middle income, 29% had public insurance, and 22% had non-English language preference. Low-to-middle-income families were more likely to incur debt (odds ratio [OR] 6.24, p < .001) and reduce consumption (OR 2.16, p = .03) than high-income families, and this association persisted in multivariable analysis. Among families with housing, food, and energy insecurity, 40%, 70%, and 39%, respectively, received hospital or government assistance specific to the experienced hardship. In subgroup analysis of families with HMH, after adjusting for income and other confounders, non-English language preference was associated with lower odds of receiving government assistance. CONCLUSIONS: After a pediatric cancer diagnosis, low-to-middle-income families are more likely to incur debt than high-income families. Most families experiencing food insecurity received some food assistance, while housing and energy assistance were less common. Future studies should investigate methods to equitably improve access to financial assistance and minimize long-term financial consequences.

Towards the development of a SARS-CoV-2 variant risk assessment tool: expert consultation on the assessment of scientific evidence on emerging variants.

A systematic approach is required for the development of an evidence-based risk assessment tool to robustly estimate the risks and implications of SARS-CoV-2 variants. We conducted a survey among experts involved in technical advisory roles for WHO to capture their assessment of the robustness of different study types that provide evidence for potential changes in transmissibility, antigenicity, virulence, treatability, and detectability of SARS-CoV-2 variants. The views of 62 experts indicated that studies could be grouped on the basis of robustness and reliability for the different risk indicators mentioned. Several study types that experts scored as providing reliable evidence and that can be performed in a timely manner were identified. Although experts from different technical areas had varying responses, there was agreement on the highest and lowest scoring study types. These findings can help to prioritise, harmonise, and optimise study designs for the further development of a systematic, evidence-based, SARS-CoV-2 variant risk assessment tool.

Disparities in household material hardship, financial toxicity, and income loss in pediatric cancer.

BACKGROUND: Based on previous reports of disparities in financial burden following a cancer diagnosis, this study aims to characterize mechanisms of disparities experienced by caregivers of children with cancer, including the impact of work flexibility and social support. METHODS: Cross-sectional survey (in English or Spanish) of caregivers of children with cancer that assessed household material hardship (HMH), financial toxicity, and income change. RESULTS: Of 156 caregivers surveyed, 32% were Hispanic and 32% were low income. Hispanic caregivers were more likely to report HMH and financial toxicity compared to non-Hispanic White and Asian (HMH: 57% vs. 21% vs. 19%, p < .001; financial toxicity: 73% vs. 52% vs. 53%, p = .07). Low- and middle-income caregivers were more likely to experience HMH and financial toxicity compared to high-income caregivers (HMH: 68% low vs. 38% middle vs. 8.7% high, p < .001; financial toxicity: 81% vs. 68% vs. 44%, p < .001). All income categories demonstrated significant increases in HMH 1 year after diagnosis. Seventeen percent reported more than 40% income loss, more of whom were low income than high income (27% vs. 12%, p = .20). Work flexibility and social support were associated with income and financial toxicity. CONCLUSION: HMH, financial toxicity, and income loss are prevalent after a child's cancer diagnosis, suggesting that screening should be incorporated into routine care. This financial burden disproportionately affects low-income and Hispanic caregivers. Further research is needed to elucidate the roles of work flexibility and social support, how safety net services are utilized by families, and how best to support families with HMH.

Race and Ethnicity in Pulmonary Function Test Interpretation: An Official American Thoracic Society Statement.

Current American Thoracic Society (ATS) standards promote the use of race and ethnicity-specific reference equations for pulmonary function test (PFT) interpretation. There is rising concern that the use of race and ethnicity in PFT interpretation contributes to a false view of fixed differences between races and may mask the effects of differential exposures. This use of race and ethnicity may contribute to health disparities by norming differences in pulmonary function. In the United States and globally, race serves as a social construct that is based on appearance and reflects social values, structures, and practices. Classification of people into racial and ethnic groups differs geographically and temporally. These considerations challenge the notion that racial and ethnic categories have biological meaning and question the use of race in PFT interpretation. The ATS convened a diverse group of clinicians and investigators for a workshop in 2021 to evaluate the use of race and ethnicity in PFT interpretation. Review of evidence published since then that challenges current practice and continued discussion concluded with a recommendation to replace race and ethnicity-specific equations with race-neutral average reference equations, which must be accompanied with a broader re-evaluation of how PFTs are used to make clinical, employment, and insurance decisions. There was also a call to engage key stakeholders not represented in this workshop and a statement of caution regarding the uncertain effects and potential harms of this change. Other recommendations include continued research and education to understand the impact of the change, to improve the evidence for the use of PFTs in general, and to identify modifiable risk factors for reduced pulmonary function.

Cardenolides, toxicity, and the costs of sequestration in the coevolutionary interaction between monarchs and milkweeds.

For highly specialized insect herbivores, plant chemical defenses are often co-opted as cues for oviposition and sequestration. In such interactions, can plants evolve novel defenses, pushing herbivores to trade off benefits of specialization with costs of coping with toxins? We tested how variation in milkweed toxins (cardenolides) impacted monarch butterfly (Danaus plexippus) growth, sequestration, and oviposition when consuming tropical milkweed (Asclepias curassavica), one of two critical host plants worldwide. The most abundant leaf toxin, highly apolar and thiazolidine ring-containing voruscharin, accounted for 40% of leaf cardenolides, negatively predicted caterpillar growth, and was not sequestered. Using whole plants and purified voruscharin, we show that monarch caterpillars convert voruscharin to calotropin and calactin in vivo, imposing a burden on growth. As shown by in vitro experiments, this conversion is facilitated by temperature and alkaline pH. We next employed toxin-target site experiments with isolated cardenolides and the monarch's neural Na+/K+-ATPase, revealing that voruscharin is highly inhibitory compared with several standards and sequestered cardenolides. The monarch's typical >50-fold enhanced resistance to cardenolides compared with sensitive animals was absent for voruscharin, suggesting highly specific plant defense. Finally, oviposition was greatest on intermediate cardenolide plants, supporting the notion of a trade-off between benefits and costs of sequestration for this highly specialized herbivore. There is apparently ample opportunity for continued coevolution between monarchs and milkweeds, although the diffuse nature of the interaction, due to migration and interaction with multiple milkweeds, may limit the ability of monarchs to counteradapt.

Screening of cardiovascular risk assessment accuracy of anthropometric indices in Indian children and adolescents.

Background: Body mass index (BMI) is the most popular anthropometric marker to define obesity and cardiometabolic risk. BMI is limited in its ability to discriminate central adiposity and other indices such as waist circumference (WC), and waist to height ratio (WHtR) could be a better choice. In this study, we aimed to evaluate the relative accuracy of these indices for the prediction of hypertension in Indian children and young adults. Methods: Anthropometric indices and blood pressure measurements were obtained in 2609 adolescent children and young adults (10-20 years) across a national residential school system. Z-scores were calculated for anthropometric parameters using the Box-Cox-Cole-Green method and World Health Organization (WHO) growth charts. Hypertension was defined using the sex, age and height specific cutoffs for systolic blood pressure. Receiver operator curve (ROC) analysis was performed to examine the predictive ability.  Results: Girls had higher BMI for age in our dataset (p < 0.001), along with higher odds for stunting (95% CI: 1.21 - 1.88) as well as central obesity (95% CI: 2.44 - 3.99). Hypertension was seen in 10.6% of the subjects, with higher age, and higher BMI or WHtR as the predictors. Prehypertension was higher in males (p <0.001). WHtR had acceptable but modest discrimination ability for hypertension (AUC > 0.6) in boys (AUC=0.62) and girls (AUC=0.66). Performance of BMI was better in boys (AUC = 0.67) but poor in girls (AUC = 0.55) Conclusion: WHtR was a better predictor of hypertension in Indian adolescent girls and could be used as an augmented parameter to BMI for a better assessment of cardiovascular risk.

Publisher Correction: Super-resolution fight club: assessment of 2D and 3D single-molecule localization microscopy software.

In the version of this paper originally published, Figure 4a contained errors that were introduced during typesetting. The bottom 11° ThunderSTORM image is an xz view but was incorrectly labeled as xy, and the low x-axis value in the four line profiles was incorrectly set as -60 instead of -50. These errors have been corrected in the PDF and HTML versions of the paper.

Super-resolution fight club: assessment of 2D and 3D single-molecule localization microscopy software.

With the widespread uptake of two-dimensional (2D) and three-dimensional (3D) single-molecule localization microscopy (SMLM), a large set of different data analysis packages have been developed to generate super-resolution images. In a large community effort, we designed a competition to extensively characterize and rank the performance of 2D and 3D SMLM software packages. We generated realistic simulated datasets for popular imaging modalities-2D, astigmatic 3D, biplane 3D and double-helix 3D-and evaluated 36 participant packages against these data. This provides the first broad assessment of 3D SMLM software and provides a holistic view of how the latest 2D and 3D SMLM packages perform in realistic conditions. This resource allows researchers to identify optimal analytical software for their experiments, allows 3D SMLM software developers to benchmark new software against the current state of the art, and provides insight into the current limits of the field.

Measuring pediatric hematology-oncology fellows' skills in humanism and professionalism: A novel assessment instrument.

BACKGROUND: Educators in pediatric hematology-oncology lack rigorously developed instruments to assess fellows' skills in humanism and professionalism. PROCEDURE: We developed a novel 15-item self-assessment instrument to address this gap in fellowship training. Fellows (N = 122) were asked to assess their skills in five domains: balancing competing demands of fellowship, caring for the dying patient, confronting depression and burnout, responding to challenging relationships with patients, and practicing humanistic medicine. An expert focus group predefined threshold scores on the instrument that could be used as a cutoff to identify fellows who need support. Reliability and feasibility were assessed and concurrent validity was measured using three established instruments: Maslach Burnout Inventory (MBI), Flourishing Scale (FS), and Jefferson Scale of Physician Empathy (JSPE). RESULTS: For 90 participating fellows (74%), the self-assessment proved feasible to administer and had high internal consistency reliability (Cronbach's α = 0.81). It was moderately correlated with the FS and MBI (Pearson's r = 0.41 and 0.4, respectively) and weakly correlated with the JSPE (Pearson's r = 0.15). Twenty-eight fellows (31%) were identified as needing support. The self-assessment had a sensitivity of 50% (95% confidence interval [CI]: 31-69) and a specificity of 77% (95% CI: 65-87) for identifying fellows who scored poorly on at least one of the three established scales. CONCLUSIONS: We developed a novel assessment instrument for use in pediatric fellowship training. The new scale proved feasible and demonstrated internal consistency reliability. Its moderate correlation with other established instruments shows that the novel assessment instrument provides unique, nonredundant information as compared to existing scales.

Defense mutualisms enhance plant diversification.

The ability of plants to form mutualistic relationships with animal defenders has long been suspected to influence their evolutionary success, both by decreasing extinction risk and by increasing opportunity for speciation through an expanded realized niche. Nonetheless, the hypothesis that defense mutualisms consistently enhance plant diversification across lineages has not been well tested due to a lack of phenotypic and phylogenetic information. Using a global analysis, we show that the >100 vascular plant families in which species have evolved extrafloral nectaries (EFNs), sugar-secreting organs that recruit arthropod mutualists, have twofold higher diversification rates than families that lack species with EFNs. Zooming in on six distantly related plant clades, trait-dependent diversification models confirmed the tendency for lineages with EFNs to display increased rates of diversification. These results were consistent across methodological approaches. Inference using reversible-jump Markov chain Monte Carlo (MCMC) to model the placement and number of rate shifts revealed that high net diversification rates in EFN clades were driven by an increased number of positive rate shifts following EFN evolution compared with sister clades, suggesting that EFNs may be indirect facilitators of diversification. Our replicated analysis indicates that defense mutualisms put lineages on a path toward increased diversification rates within and between clades, and is concordant with the hypothesis that mutualistic interactions with animals can have an impact on deep macroevolutionary patterns and enhance plant diversity.

Re-evaluating the costs and limits of adaptive phenotypic plasticity.

When the optimal phenotype differs among environments, adaptive phenotypic plasticity can evolve unless constraints impede such evolution. Costs and limits of plasticity have been proposed as important constraints on the evolution of plasticity, yet confusion exists over their distinction. We attempt to clarify these concepts by reviewing their categorization and measurement, highlighting how costs and limits are defined in different currencies (and may describe the same phenomenon). Conclusions from studies that measure the costs of plasticity have been equivocal, but we caution that these conclusions may be premature owing to a potentially common correlation between environment-specific trait values and the magnitude of trait plasticities (i.e. multi-collinearity) that results in imprecise and/or biased estimates of the costs. Meanwhile, our understanding of the limits of plasticity, and how they may be underlain by the costs of plasticity, is still in its infancy. Based on our re-evaluation of these constraints, we discuss areas for future research.

Ecological genetics of an induced plant defense against herbivores: additive genetic variance and costs of phenotypic plasticity.

Adaptive phenotypic plasticity in chemical defense is thought to play a major role in plant-herbivore interactions. We investigated genetic variation for inducibility of defensive traits in wild radish plants and asked if the evolution of induction is constrained by costs of phenotypic plasticity. In a greenhouse experiment using paternal half-sibling families, we show additive genetic variation for plasticity in glucosinolate concentration. Genetic variation for glucosinolates was not detected in undamaged plants, but was significant following herbivory by a specialist herbivore, Pieris rapae. On average, damaged plants had 55% higher concentrations of glucosinolates compared to controls. In addition, we found significant narrow-sense heritabilities for leaf size, trichome number, flowering phenology, and lifetime fruit production. In a second experiment, we found evidence of genetic variation in induced plant resistance to P. rapae. Although overall there was little evidence for genetic correlations between the defensive and life-history traits we measured, we show that more plastic families had lower fitness than less plastic families in the absence of herbivory (i.e., evidence for genetic costs of plasticity). Thus, there is genetic variation for induction of defense in wild radish, and the evolution of inducibility may be constrained by costs of plasticity.

COSTS OF INDUCED RESPONSES AND TOLERANCE TO HERBIVORY IN MALE AND FEMALE FITNESS COMPONENTS OF WILD RADISH.

Theory predicts that plant defensive traits are costly due to trade-offs between allocation to defense and growth and reproduction. Most previous studies of costs of plant defense focused on female fitness costs of constitutively expressed defenses. Consideration of alternative plant strategies, such as induced defenses and tolerance to herbivory, and multiple types of costs, including allocation to male reproductive function, may increase our ability to detect costs of plant defense against herbivores. In this study we measured male and female reproductive costs associated with induced responses and tolerance to herbivory in annual wild radish plants (Raphanus raphanistrum). We induced resistance in the plants by subjecting them to herbivory by Pieris rapae caterpillars. We also induced resistance in plants without leaf tissue removal using a natural chemical elicitor, jasmonic acid; in addition, we removed leaf tissue without inducing plant responses using manual clipping. Induced responses included increased concentrations of indole glucosinolates, which are putative defense compounds. Induced responses, in the absence of leaf tissue removal, reduced plant fitness when five fitness components were considered together; costs of induction were individually detected for time to first flower and number of pollen grains produced per flower. In this system, induced responses appear to impose a cost, although this cost may not have been detected had we only quantified the traditionally measured fitness components, growth and seed production. In the absence of induced responses, 50% leaf tissue removal, reduced plant fitness in three out of the five fitness components measured. Induced responses to herbivory and leaf tissue removal had additive effects on plant fitness. Although plant sibships varied greatly (49-136%) in their level of tolerance to herbivory, costs of tolerance were not detected, as we did not find a negative association between the ability to compensate for damage and plant fitness in the absence of damage. We suggest that consideration of alternative plant defense strategies and multiple costs will result in a broader understanding of the evolutionary ecology of plant defense.