Optimizing assessment of CD30 expression in Hodgkin lymphoma by controlling for low expression

Since the approval of brentuximab vedotin (BV), assessment of CD30 status by immunohistochemistry gained increasing importance in the clinical management of patients diagnosed with CD30expressing lymphomas, including classical Hodgkin lymphoma (CHL). Paradoxically, patients with low or no CD30 expression respond to BV. This discrepancy may be due to lack of standardization in CD30 staining methods. In this study, we examined 29 cases of CHL and 4 cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) for CD30 expression using a staining protocol that was designed to detect low CD30 expression levels, and an evaluation system similar to the Allred scoring system used for breast cancer evaluation. For CHL, 10% of cases had low scores and 3% were CD30 negative, with 3 cases in which the majority of tumor cells showed very weak staining. Unexpectedly, one of four cases of NLPHL was positive. We demonstrate intra-patient heterogeneity in CD30 expression levels and staining patterns in tumor cells. Three CHL cases with weak staining may have been missed without the use of control tissue for low expression. Thus, standardization of CD30 immunohistochemical staining with use of known lowexpressing controls may aid in proper CD30 assessment and subsequent therapeutic stratification of patients

Apo CIII Proteoforms, Plasma Lipids, and Cardiovascular Risk in MESA

BackgroundApo CIII (apolipoprotein CIII) is an important regulator of triglyceride metabolism and was associated with cardiovascular risk in several cohorts. It is present in 4 major proteoforms, a native peptide (CIII0a), and glycosylated proteoforms with zero (CIII0b), 1 (CIII1, most abundant), or 2 (CIII2) sialic acids, which may differentially modify lipoprotein metabolism. We studied the relationships of these proteoforms with plasma lipids and cardiovascular risk.MethodsApo CIII proteoforms were measured by mass spectrometry immunoassay in baseline plasma samples of 5791 participants of Multi-Ethnic Study of Atherosclerosis, an observational community-based cohort. Standard plasma lipids were collected for up to 16 years and cardiovascular events (myocardial infarction, resuscitated cardiac arrest, or stroke) were adjudicated for up to 17 years.ResultsApo CIII proteoform composition differed by age, sex, race and ethnicity, body mass index, and fasting glucose. Notably, CIII1 was lower in older participants, men and Black and Chinese (versus White) participants, and higher in obesity and diabetes. In contrast, CIII2 was higher in older participants, men, Black, and Chinese persons, and lower in Hispanic individuals and obesity. Higher CIII2 to CIII1 ratio (CIII2/III1) was associated with lower triglycerides and higher HDL (high-density lipoprotein) in cross-sectional and longitudinal models, independently of clinical and demographic risk factors and total apo CIII. The associations of CIII0a/III1 and CIII0b/III1 with plasma lipids were weaker and varied through cross-sectional and longitudinal analyses. Total apo CIII and CIII2/III1 were positively associated with cardiovascular disease risk (n=669 events, hazard ratios, 1.14 [95% CI, 1.04-1.25] and 1.21 [1.11-1.31], respectively); however, the associations were attenuated after adjustment for clinical and demographic characteristics (1.07 [0.98-1.16]; 1.07 [0.97-1.17]). In contrast, CIII0b/III1 was inversely associated with cardiovascular disease risk even after full adjustment including plasma lipids (0.86 [0.79-0.93]).ConclusionsOur data indicate differences in clinical and demographic relationships of apo CIII proteoforms, and highlight the importance of apo CIII proteoform composition in predicting future lipid patterns and cardiovascular disease risk

Quantification and Analysis of Micro-Level Activities Data from Children Aged 1-12 Years Old for Use in the Assessments of Exposure to Recycled Tire on Turf and Playgrounds.

BACKGROUND: There are growing health concerns about exposure to toxicants released from recycled tire rubber, which is commonly used in synthetic turf and playground mats. To better estimate children\u27s exposure and risk from recycled tire rubber used in synthetic turf and playground mats, there is a need to collect detailed accurate information on mouthing activity and dermal contact behaviors. The objective of this study was to quantify and analyze micro-level activity time series (MLATS) data from children aged 1-12 years old while playing (non-sport-related games) at turf-like locations and playgrounds. Another objective was to estimate the incidental ingestion rate of rubber crumb among children. METHODS: Hand and mouth contact frequency, hourly duration, and median contact duration with different objects were calculated for children playing on turf (i.e., parks, lawns, and gardens) (n = 56) and for children playing on playground structures (n = 24). Statistically significant differences between males and females as well as children\u27s age groups were evaluated. The daily incidental ingestion rate of rubber crumb was calculated. RESULTS: For children playing on turf, there were significant differences between younger (1-6 y) and older (7-12 y) children for the mouthing median duration with non-dietary objects and all objects. For children playing on playground structures, we found significant mouthing frequency differences between younger (1-6 y) and older children (7-12 y) with all objects, and for mouthing median duration with non-dietary objects. There were no significant differences between males and females playing on artificial turf-like surfaces or playground mats. Our estimated mean incidental ingestion rate was 0.08, 0.07, and 0.08 g rubber crumb/day for children DISCUSSION: our results suggest that age and contact duration should be considered in risk assessment models to evaluate mouthing activities when children are playing on artificial turf surfaces or playground mats

What a mix! Volatile organic compounds and worker exposure in small business beauty salons in Tucson, Arizona

IntroductionSmall business beauty salons have volatile organic compounds (VOCs) in their workplace air. VOCs are present as ingredients in beauty or hair products. They may also form because of chemical reactions, where thermal-styling elements accelerate the volatilization of these compounds. Uncertainties remain about the relationship between air pollutant concentrations and the variety of beauty salon activities in a work shift. Investigating these associations can help determine high-risk services, associated products, and at-risk workers.MethodsIn this exploratory study, female community health workers recruited beauty salons from target zip codes in predominately Latino neighborhoods, including primarily Spanish-speaking small businesses. We collected salon chemical inventories, business characteristics, and participant activity logs to understand how chemicals and activities influence the total and specific VOC concentrations. We sampled personal total VOCs and specific VOCs from the same shop during the participant work shift. We also measured personal total VOCs for four work shifts per shop.ResultsA linear mixed effects model of log VOCs on the fixed effect of activity and the random effects of salon and shift within the salon showed that the variance between salons explains over half (55%) of the total variance and is 4.1 times bigger than for shifts within salons. Summa canisters detected 31 specific VOCs, and hazard scores ranged between 0 and 4.3. 2-Propanol (isopropyl alcohol) was the only VOC detected in all shifts of all salons.DiscussionIn this study, differences in VOC measurements were primarily between salons. These differences may result from differences in ventilation, services rendered, and product lines applied

The role of small airway dysfunction in asthma control and exacerbations:a longitudinal, observational analysis using data from the ATLANTIS study

Background Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life.Methods In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed.Findings 773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0.20-0.25, p<0.0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life.Interpretation Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations. Copyright (C) 2022 Elsevier Ltd. All rights reserved

Community-level characteristics and environmental factors of child respiratory illnesses in Southern Arizona

Abstract Background Lower respiratory illnesses (LRIs) and asthma are common diseases in children 0.05). Conclusions Our study revealed complex, multi-factorial associations between predictors and outcomes. Findings indicate that many rural areas with lower SES have distinct factors for childhood respiratory diseases that require further investigation. County-wide differences in maternal characteristics or agricultural land uses (not tested here) may also play a role in Pima County residence protecting against hospitalizations, when compared to Maricopa County. By better understanding this and other relationships, more focused public health interventions at the community level could be developed to reduce and better control these diseases in children <5 years, who are more physiologically vulnerable

Predictive Inference and Scientific Reproducibility

Most statistical analyses use hypothesis tests or estimation about parameters to form inferential conclusions. I think this is noble, but misguided. The point of view expressed here is that observables are fundamental, and that the goal of statistical modeling should be to predict future observations, given the current data and other relevant information. Further, the prediction of future observables provides multiple advantages to practicing scientists, and to science in general. These include an interpretable numerical summary of a quantity of direct interest to current and future researchers, a calibrated prediction of what's likely to happen in future experiments, a prediction that can be either "corroborated" or "refuted" through experimentation, and avoidance of inference about parameters; quantities that exists only as convenient indices of hypothetical distributions. Finally, the predictive probability of a future observable can be used as a standard for communicating the reliability of the current work, regardless of whether confirmatory experiments are conducted. Adoption of this paradigm would improve our rigor for scientific accuracy and reproducibility by shifting our focus from "finding differences" among hypothetical parameters to predicting observable events based on our current scientific understanding.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]