Motherhood and Income Inequality: A Cross-Country Analysis

This paper attempts to analyze the gender wage gap in the United States and other economically developed nations. Despite a significant convergence of the income gap between men and women in the US, recent years have seen a lag in this convergence. This paper aims to specifically see the costs of motherhood on the occupational decisions of women, their career path, and the earning penalties as a result of children. I analyze government-mandated paid maternity leave and new parent protection rights and their impact on income inequality as well as their potential to lessen the gap

Postnatal steroids to prevent bronchopulmonary dysplasia in high-risk preterm infants

Bronchopulmonary dysplasia (BPD) is diagnosed in approximately 40% of extremely preterm infants, those born before 28 weeks’ gestational age, and affects roughly 10,000 to 15,000 infants annually in the United States alone. Current treatment of BPD aims to not only aid in the survival of the infant but to also minimize further lung damage and promote physiologic growth to enhance lung development and repair. As the pathogenesis of the disease is multifactorial, including pre-, peri-, and postnatal factors, treatment and prevention approaches to BPD are diverse and include both medical treatment and ventilation strategies. Late postnatal steroids (> 7 days of life) have been proven to facilitate extubation and reduce the incidence of BPD in preterm infants. However, there is evidence that the use of steroids may contribute to increased rates of neurological impairment, including increased incidence of cerebral palsy. Given these findings, the American Academy of Pediatrics (AAP) guidelines recommend against the routine use of systemic steroids in the prevention of BPD and instead argues its use should be limited to infants who are considered extremely high-risk. The aim of this study is to determine whether the use of postnatal dexamethasone decreases the risk of developing BPD in a subset of high-risk infants, those with a concomitant diagnosis of necrotizing enterocolitis or late onset sepsis. A sample size of 200 extremely preterm infants with either necrotizing enterocolitis (NEC) and/or sepsis will be enrolled in a multi-center double-blinded randomized controlled trial comparing a low-dose dexamethasone taper and saline placebo. Infants will be evaluated for the development of BPD based on respiratory support and supplemental oxygen requirement at 36 weeks’ post-menstrual age (PMA). Infants will also be evaluated for presence of neurodevelopmental outcomes at 18- to 22-months follow-up. The results of this proposed study will build the evidence base for the safety and efficacy of postnatal steroids in the prevention of BPD in a subset of high risk, extremely preterm infants. This will help to establish a more detailed characterization of infants for which the benefits of steroids outweigh the risks. The results will enable clinicians to make more informed decisions regarding the medical care of extremely preterm infants and more accurately counsel parents on the incidence of subsequent BPD development, as well as long-term morbidities

MET tyrosine kinase receptor expression and amplification as prognostic biomarkers of survival in gastroesophageal adenocarcinoma

MET gene amplification and Met protein overexpression may be associated with a poor prognosis. The MET/Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry-based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of MET/Met in gastroesophageal adenocarcinoma (GEC)

MET as a prognostic biomarker of survival in a large cohort of patients with gastroesophageal cancer (GEC)

Background: Estimates of the frequency of genomic/proteomic alterations in MET in solid tumors vary widely, but a growing body of evidence suggests that MET amplification and/or Met expression are biomarkers for poor prognosis. We examined both MET gene copy number and Met protein expression as potential prognostic biomarkers for survival in a large set of GEC samples with full clinical annotations (staging, HER2 status, treatment, and overall survival). Methods: Formalin-fixed, paraffin-embedded (FFPE) GEC samples (N = 394) primarily from early-stage tumors were collected in the United States and Italy. Samples were analyzed by fluorescence in situ hybridization (FISH) for MET gene amplification (Dako MET IQFISH probe mix, research use only) and by immunohistochemistry (IHC) for Met protein expression (Dako Met IHC assay, MET4 antibody, investigational use only). All assays were performed according to the manufacturer’s instructions. Samples with a MET/CEP 7 ratio ≥ 2.0 were considered amplified, whereas samples with ≥ 25% Met tumor membrane staining by IHC ( ≥ 1+ intensity) were considered Met positive. Spearman’s rank correlation coefficient was used to assess correlations between parameters. Cox proportional hazards models and Kaplan-Meier estimates were applied to explore relationships between MET, overall survival, and other clinical characteristics. Results: MET gene copy number variation ( ≥ 5 copies) was observed in 18 of 344 samples (5.2%), and MET gene amplification (MET/CEP 7≥ 2.0) was observed in 16 of 344 samples (4.7%). Of the 332 evaluable IHC samples, 117 (35.2%) were positive for Met protein expression. There was considerable overlap between MET amplification and Met expression; 12 of 15 MET-amplified samples (80.0%) were positive for Met expression.Survival analyses showed that both MET gene amplification and Met IHC positivity were prognostic of poor outcomes. Conclusions: MET amplification was observed in ~5% of this large set of GEC samples. Prevalence of MET amplification and Met expression were similar to those found in previously published studies. Our results indicate that MET gene amplification and Met protein expression are prognostic of poor outcomes in GEC

Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH

Trastuzumab has shown a survival benefit in cases of Her2-positive gastroesophageal cancer (GEC). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) currently determine eligibility for trastuzumab-based therapy. However, these low-throughput assays often produce discordant or equivocal results. We developed a targeted proteomic assay based on selected reaction monitoring mass spectrometry (SRM-MS) and quantified levels (amol/mu g) of Her2-SRM protein in cell lines (n = 27) and GEC tissues (n = 139). We compared Her2-SRM protein expression with IHC/FISH, seeking to determine optimal SRM protein expression cutoffs in order to identify HER2 gene amplification. After demonstrating assay development, precision, and stability, Her2-SRM protein measurement was observed to be highly concordant with the HER2/CEP17 ratio, particularly in a multivariate regression model adjusted for SRM expression of the covariates Met, Egfr, Her3, and HER2 heterogeneity, as well as their interactions (cell lines r (2) = 0.9842; FFPE r (2) = 0.7643). In GEC tissues, Her2-SRM protein was detected at any level in 71.2 % of cases. ROC curves demonstrated that Her2-SRM protein levels have a high specificity (100 %) at an upper-level cutoff of > 750 amol/A mu g and sensitivity of 75 % at a lower-level cutoff of < 450 amol/mu g for identifying HER2 FISH-amplified tumors. An "equivocal zone" of 450-750 amol/A mu g of Her2-SRM protein was analogous to IHC2+ but represented fewer cases (9-16 % of cases versus 36-41 %). Compared to IHC, targeted SRM-Her2 proteomics provided more objective and quantitative Her2 expression with excellent HER2/CEP17 FISH correlation and fewer equivocal cases. Along with its multiplex capability for other relevant oncoproteins, these results demonstrate a refined HER2 protein expression assay for clinical application

Author Correction: Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition

In the Supplementary Information originally published with this article, a lane was missing in the β-actin blot in Supplementary Fig. 2. The lane has been added. The error has been corrected in the Supplementary Information associated with this article