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Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. S. received grant support from GSK, Trudell Medical Int, consulting fees and/or honoraria from AstraZeneca, BI, Kamada, Sanofi, and Insmed. J. D. C. received grant support from AstraZeneca, Genentech, Gilead sciences, GSK, Grifols, Boehringer Ingelheim, Insmed, Novartis; consulting fees from AstraZeneca, Chiesi, GSK, Insmed, Novartis, Pfizer, Grifols, Boehringer Ingelheim, Janssen, Antabio, Zambon. None declared (O. S., N. S., R. F., A. J., N. O., P. S., J. U. S. J., M. C., P. M., C. N. M., W. S.).

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements., Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV 1 , forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV 1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV 1 /FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV 1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year., Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV 1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV 1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV 1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV 1 /FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001)., Interpretation: If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity., Funding: The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme., Competing Interests: Declaration of interests JPA has received speaker fees from Pulmonx, travel costs from Boehringer Ingelheim to deliver a lecture, and travel costs from GlaxoSmithKline to attend an advisory board meeting. YÇ received personal fees from Boehringer Ingelheim, AstraZeneca, and Sanofi Genzyme. HB has received payment from AstraZeneca and Boehringer Ingelheim for presentations made at scientific meetings. MvdB has received institutional research grants from GlaxoSmithKline, Roche, Genentech, and Novartis. GB has received honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Novartis, Sanofi, and TEVA. OCB has received grants or contracts, consulting fees, and payment or honoraria from AstraZeneca, Abbvie, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, MSD, Novartis, Roche, Takeda, and TEVA for lectures, presentations, speakers bureaus, manuscript writing, or educational events. RF has received research grants from GlaxoSmithKline, Menarini, AstraZeneca, ISC-III, and the Spanish Health Service, consulting fees from GlaxoSmithKline, and honoraria from Chiesi Farmaceutici. SH has received grants or contracts, consulting fees, and payment or honoraria from AstraZeneca, Abbvie, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, MSD, Novartis, Roche, Takeda, and TEVA for lectures, presentations, speakers bureaus, manuscript writing, or educational events. AL has received payment for lectures from Boehringer Ingelheim and travel costs from Novartis and AstraZeneca to attend meetings, has participated in an AstraZeneca advisory board, has contributed to the Norwegian Primary Care Respiratory Group, and has been a member of the Norwegian Health Directorate. BL has received grants from AstraZeneca and ThermoFisher and has participated in a Sanofi advisory board. SAAV has received support from AstraZeneca to attend meetings. SRAW has received travel grants from GlaxoSmithKline. PL has received institutional grants, personal consulting fees, and personal lecture fees from AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim. GCD has received institutional grants from Genentech and AstraZeneca, book chapter royalties from Elsevier, and payment from AstraZeneca and Novartis for participation in advisory boards. JAW has received institutional grants from GlaxoSmithKline, AstraZeneca, Chiesi Farmaceutici, Boehringer Ingelheim, Novartis, and Genentech, and has participated in a Virtus data and safety monitoring board. JV is supported by the National Institute for Health Research Manchester Biomedical Research Centre, has received a research grant from Boehringer Ingelheim, honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, and Novartis for presentations at meetings, and honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Novartis, and TEVA for participation in advisory boards, is a member of the Panel for Clinical and Translational Research for the Novo Nordisk Foundation, has chaired the Asthma UK Research Review Panel, and is a member of the Medical and Chemicals Technical Options Committee for the Montreal Protocol, the UN Environment Programme. LEGWV has received institutional grants from AstraZeneca, personal payments from AstraZeneca, GlaxoSmithKline, Boehringer, Linde, Novartis, Menarini, and Zambon for lectures, presentations, speakers bureaus, manuscript writing, or educational events, personal payments from AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim for participation on data safety monitoring boards or advisory boards, and payment from Chiesi Farmaceutici for medical writing. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: We sought to characterize the variability of CCNE1 amplification among metastatic sites of CCNE1 amplified high grade serous carcinoma (HGSC) cases to investigate the feasibility of targeting this alteration for therapeutic purposes., Methods: Patients with CCNE1 amplified HGSC who underwent surgical cytoreduction with metastatic sites were identified from institutional molecular profiling reports and a population of HGSC cases screened using digital droplet PCR (ddPCR). Cases with normal CCNE1 copy number were included as controls. Slides from metastatic sites were cut from formalin-fixed paraffin-embedded tissue blocks, dissected for tumor of > 50% purity, and underwent DNA extraction. CCNE1 copy number was determined by ddPCR. Tumor purity was confirmed with mutant TP53 allele fraction from targeted massively parallel sequencing., Results: Four of 15 patients from an institutional database screened by ddPCR were found to have CCNE1 amplification. Three additional patients were identified from a query of institutional commercial clinical reports. Among these 7 CCNE1 amplified cases (2 uterine, 5 ovarian), 5 showed preservation of CCNE1 amplification (copy number > 5) among all metastatic sites. The remaining 2 cases had multiple metastatic sites without preserved CCNE1 amplification. Non-amplified cases had predominantly normal CCNE1 copy number across metastatic sites., Conclusions: CCNE1 amplification is an early genomic event in HGSC and is preserved in most metastatic sites suggesting a uniform response to pathway targeting therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

This study examined whether maternal adiposity, acculturation, and perceived-ideal body size discrepancy for daughters were associated with daughters' engagement in unhealthy weight control behaviors. A total of 97 Hispanic mother-daughter dyads completed surveys, rated a figure scale, and had their height, weight, and adiposity assessed. Mothers (M age =39.00, SD=6.20 years) selected larger ideal body sizes for their daughters (M age =11.12, SD=1.53 years) than their daughters selected for themselves. Mothers had a smaller difference between their perception of their daughters' body size and ideal body size compared to the difference between their daughters' selection of their perceived and ideal body size. More acculturated mothers and those mothers with larger waist-to-hip ratios were more likely to have daughters who engaged in unhealthy weight control behaviors. These findings highlight the relevant role that maternal acculturation and adiposity may have in influencing daughters' unhealthy weight control behaviors., (Published by Elsevier Ltd.)

The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS and normal myometrium (NL) to identify clinically relevant molecular subtypes. Discovery cases included 29 NL and 23 ULMS specimens. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods. Fourteen NL and 44 ULMS independent archival samples were used for external validation. Molecular subgroups were correlated with clinical outcome. Pathway analyses of differentially expressed genes between ULMS and NL samples identified overrepresentation of cell cycle regulation, DNA repair, and genomic integrity. External validation confirmed differential expression in 31 genes (P < 4.4 × 10(-4), Bonferroni corrected), with 84% of the overexpressed genes, including CDC7, CDC20, GTSE1, CCNA2, CCNB1, and CCNB2, participating in cell cycle regulation. Unsupervised clustering of ULMS identified two clades that were reproducibly associated with progression-free (median, 4.0 vs 26.0 months; P = .02; HR, 0.33) and overall (median, 18.2 vs 77.2 months; P = .04; HR, 0.33) survival. Cell cycle genes play a key role in ULMS sarcomagenesis, providing opportunities for therapeutic targeting. Reproducible molecular subtypes associated with clinical outcome may permit individualized adjuvant treatment after clinical trial validation., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

This study examined neighborhood safety as perceived by children (mean age=10 years) and their mothers, and its association with children's physical activity. For all eight safety items examined, children perceived their environment as less dangerous than mothers (p<0.05). None of the multiple regression models predicting children's physical activity by safety perceptions were significant (p>0.10). The maternal perception model explained the highest percentage of variance (R(2)=0.26), compared to the children's perception model (R(2)=0.22). Findings suggest that future studies should explore relations between self-reported and objectively measured safety barriers to Hispanic youth walking and cycling., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The relationship between parental socialization strategies and child smoking behavior was examined among 170 Latino parents and 85 index children. Maternal support was negatively associated with child smoking whereas siblings' and friends' smoking were positively associated. Studies with larger samples of Latino families are needed to replicate these findings.