Cost-Effectiveness of Primary versus Secondary Prophylaxis with Pegfilgrastim in Women with Early-Stage Breast Cancer Receiving Chemotherapy

AbstractObjectiveProphylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. We estimated the incremental cost-effectiveness of G-CSF pegfilgrastim primary (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) versus secondary (only after an FN event) prophylaxis in women with early-stage breast cancer receiving myelosuppressive chemotherapy with a ≥20% FN risk.MethodsA decision-analytic model was constructed from a health insurer's perspective with a lifetime study horizon. The model considers direct medical costs and outcomes related to reduced FN and potential survival benefits because of reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values.ResultsThe incremental cost-effectiveness ratio (ICER) of pegfilgrastim as primary versus secondary prophylaxis was $48,000/FN episode avoided. Adding survival benefit from avoiding FN mortality yielded an ICER of$110,000/life-year gained (LYG) or $116,000/quality-adjusted life-year (QALY) gained. The most influential factors included FN case-fatality, FN relative risk reduction from primary prophylaxis, and age at diagnosis.ConclusionsCompared with secondary prophylaxis, the cost-effectiveness of pegfilgrastim as primary prophylaxis may be equivalent or superior to other commonly used supportive care interventions for women with breast cancer. Further assessment of the direct impact of G-CSF on short- and long-term survival is needed to substantiate these findings

Habits of Mind: Designing Courses for Student Success

Although content knowledge remains at the heart of college teaching and learning, forward-thinking instructors recognize that we must also provide 21st-century college students with transferable skills (sometimes called portable intellectual abilities) to prepare them for their futures (Vazquez, 2020; Ritchhart, 2015; Venezia & Jaeger, 2013; Hazard, 2012). To “grow their capacity as efficacious thinkers to navigate and thrive in the face of unprecedented change” (Costa et al., 2023), students must learn and improve important study skills and academic dispositions throughout their educational careers. If we do not focus on skills-building in college courses, students will not be prepared for the challenges that await them after they leave institutions of higher education. If students are not prepared for these postsecondary education challenges, then it is fair to say that college faculty have failed them

Holiday Concert, Home for the Holidays

Kennesaw State University School of Music presents Holiday Concert, Home for the Holidays.https://digitalcommons.kennesaw.edu/musicprograms/1433/thumbnail.jp

Supernova 2018cuf : a type iip supernova with a slow fall from plateau

We present multiband photometry and spectroscopy of SN 2018cuf, a Type IIP ("P"for plateau) supernova (SN) discovered by the Distance Less Than 40 Mpc Survey within 24 hr of explosion. SN 2018cuf appears to be a typical SN IIP, with an absolute V-band magnitude of -16.73 ± 0.32 at maximum and a decline rate of 0.21 ± 0.05 mag/50 days during the plateau phase. The distance of the object was constrained to be 41.8 ± 5.7 Mpc by using the expanding photosphere method. We used spectroscopic and photometric observations from the first year after the explosion to constrain the progenitor of SN 2018cuf using both hydrodynamic light-curve modeling and late-time spectroscopic modeling. The progenitor of SN 2018cuf was most likely a red supergiant of about 14.5 Me that produced 0.04 ± 0.01 Me 56Ni during the explosion. We also found ∼0.07 Me of circumstellar material (CSM) around the progenitor is needed to fit the early light curves, where the CSM may originate from presupernova outbursts. During the plateau phase, high-velocity features at ∼11,000 km s-1 were detected in both the optical and near-infrared spectra, supporting the possibility that the ejecta were interacting with some CSM. A very shallow slope during the postplateau phase was also observed, and it is likely due to a low degree of nickel mixing or the relatively high nickel mass in the SN.Fil: Dong, Yize. University of California at Davis; Estados UnidosFil: Valenti, S.. University of California at Davis; Estados UnidosFil: Bostroem, K. A.. University of California at Davis; Estados UnidosFil: Sand, D. J.. University of Arizona; Estados UnidosFil: Andrews, Jennifer E.. University of Arizona; Estados UnidosFil: Galbany, Lluís. Universidad de Granada; EspañaFil: Jha, Saurabh W.. State University of New Jersey; Estados UnidosFil: Eweis, Youssef. State University of New Jersey; Estados UnidosFil: Kwok, Lindsey. State University of New Jersey; Estados UnidosFil: Hsiao, Eric. Florida State University; Estados UnidosFil: Davis, Scott. Florida State University; Estados UnidosFil: Brown, Peter J.. Texas A&M University; Estados UnidosFil: Kuncarayakti, H.. University of Turku; FinlandiaFil: Maeda, Keiichi. Kyoto University; JapónFil: Rho, Jeonghee. SETI Institute; Estados UnidosFil: Amaro, R. C.. University of Arizona; Estados UnidosFil: Anderson, J. P.. European Southern Observatory Chile; ChileFil: Arcavi, Iair. Universitat Tel Aviv; IsraelFil: Burke, Jamison. University of California; Estados UnidosFil: Dastidar, Raya. Aryabhatta Research Institute of observational sciences; IndiaFil: Folatelli, Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Haislip, Joshua. University of North Carolina at Chapel Hill; Estados UnidosFil: Hiramatsu, Daichi. University of California; Estados UnidosFil: Hosseinzadeh, Griffin. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Howell, D. Andrew. University of California; Estados UnidosFil: Jencson, J.. University of Arizona; Estados UnidosFil: Kouprianov, Vladimir. University of North Carolina at Chapel Hill; Estados UnidosFil: Lundquist, M.. University of Arizona; Estados UnidosFil: Lyman, J. D.. University of Warwick; Reino UnidoFil: McCully, Curtis. University of California; Estados Unido

Determination of quantitative trait loci (QTL) for early maturation in rainbow trout (Oncorhynchus mykiss)

To identify quantitative trait loci (QTL) influencing early maturation (EM) in rainbow trout (Oncorhynchus mykiss), a genome scan was performed using 100 microsatellite loci across 29 linkage groups. Six inter-strain paternal half-sib families using three inter-strain F(1) brothers (approximately 50 progeny in each family) derived from two strains that differ in the propensity for EM were used in the study. Alleles derived from both parental sources were observed to contribute to the expression of EM in the progeny of the brothers. Four genome-wide significant QTL regions (i.e., RT-8, -17, -24, and -30) were observed. EM QTL detected on RT-8 and -24 demonstrated significant and suggestive QTL effects in both male and female progeny. Furthermore, within both male and female full-sib groupings, QTL on RT-8 and -24 were detected in two or more of the five parents used. Significant genome-wide and several strong chromosome-wide QTL for EM localized to different regions in males and females, suggesting some sex-specific control. Namely, QTL detected on RT-13, -15, -21, and -30 were associated with EM only in females, and those on RT-3, -17, and -19 were associated with EM only in males. Within the QTL regions identified, a comparison of syntenic EST markers from the rainbow trout linkage map with the zebrafish (Danio rerio) genome identified several putative candidate genes that may influence EM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10126-008-9098-5) contains supplementary material, which is available to authorized users

Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells

The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway. Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription.Here, however, we observe that in primary cultures of breast and ovarian epithelial cells, phosphorylation and activation of ERK1/2 are disassociated from nuclear translocalization and transcription of downstream targets, such as c-Fos, suggesting that nuclear translocation is limited in primary cells. Accordingly, in import assays in vitro, primary cells showed a lower import activity for ERK1/2 than cancer cells, in which activated MAPK readily translocated into the nucleus and activated c-Fos expression. Primary cells express lower levels of nuclear pore complex proteins and the nuclear transport factors, importin B1 and importin 7, which may explain the limiting ERK1/2 import found in primary cells. Additionally, reduction in expression of nucleoporin 153 by siRNA targeting reduced ERK1/2 nuclear activity in cancer cells.ERK1/2 activation is dissociated from nuclear entry, which is a rate limiting step in primary cells and in vivo, and the restriction of nuclear entry is disrupted in transformed cells by the increased expression of nuclear pores and/or nuclear transport factors

High-Content, High-Throughput Analysis of Cell Cycle Perturbations Induced by the HSP90 Inhibitor XL888

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine