Plasma thymidine kinase 1 activity and outcome of ER+ HER2- metastatic breast cancer patients treated with palbociclib and endocrine therapy.

PURPOSE: Previous cohort studies have reported plasma TK1 activity (pTKa) as a potential prognostic biomarker in estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). In this prospective study, we report here the prognostic impact of pTKa in ER+/HER2- MBC patients treated with endocrine therapy and CDK4/6 inhibitor. EXPERIMENTAL DESIGN: Patients were included into the prospective, ethics committee-approved ALCINA study (NCT02866149). Eligibility criteria were patients with ER+/HER2- MBC treated at Institut Curie with endocrine therapy and palbociclib. Plasma samples were obtained at baseline and after 4 weeks of treatment. pTKa was quantified by the DiviTum® assay (Biovica, Sweden). RESULTS: From May 2016 to August 2018, 103 patients treated with endocrine therapy and palbociclib were included. Patients had received a median of two prior systemic therapies for MBC (range 0-14). Median follow-up was 13.8 months (range 6-31), with median PFS and OS of 9.6 months (95%CI [7.0-11.3]) and 28 months (95%CI [23-not reached]), respectively. Median baseline pTKa was 292 Du/L (range 20-27,312 Du/L, IQR [89-853]). After adjusting for other prognostic factors, baseline pTKa remained an independent prognostic factor for both PFS (HR = 1.3 95%CI [1.1-1.4], p = 0.0005) and OS (HR = 1.3 95%CI [1.2-1.6], p < 0.0001), and 4-week pTKa was associated with OS (HR = 1.6 95%CI [1.3-2], p < 0.0001). That survival prediction was significantly improved by the addition of baseline pTKa to clinicopathological characteristics. Adding pTKa changes at 4 weeks to baseline pTKa did not further increase survival prediction. CONCLUSION: This study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/HER2- MBC patients treated with endocrine therapy and palbociclib.

Up on the hill: the experiences of adaptive snow sports.

INTRODUCTION: Literature supports the benefits of involvement for people with disabilities in adaptive snow sports. However, the literature is lacking in understanding the experiences of those involved in these programs or understanding what facilitates participation in adaptive snow sports. OBJECTIVES: This project aims to (1) explore the experiences of people with disabilities participating in adaptive snow sports; and (2) to explore the factors which impact participation in adaptive snow sports. MATERIALS AND METHODS: We recruited 20 former and current participants from an adaptive snow sports program using a volunteer recruitment strategy. Data were collected through individual or dyadic semi-structured interviews and on-site observations. Data were transcribed verbatim and thematic data analyses were conducted. RESULTS: Three main themes emerged from this study: (1) mountain top moments, which described the outcomes of successful participation in adaptive snow sports; (2) finding your line, which refers to the facilitators involved in adaptive snow sports participation; and (3) icy slopes and trailblazing, which includes the social, physical, and institutional environmental factors that impede quality participation. CONCLUSION: Adaptive snow sports provide people with disabilities opportunities to develop community, engage in new and meaningful experiences, and to overcome challenges. The accounts given by people with disabilities of their experiences in adaptive snow sports suggest that key factors for participation are the involvement of student-centered instructors and the provision of adaptive equipment.Implications for rehabilitationAdaptive snow sports provide opportunities for people with disabilities to learn new and meaningful skills, develop meaningful relationships, and enjoy the outdoors.Knowledgeable instructors who are able to meet people with disabilities unique needs is an essential component to adaptive snow sport programs.Additionally, the provision of adaptive equipment is an important aspect of adaptive snow sport programs.

Body residues: a key variable to analyze toxicity tests with Chironomus riparius exposed to copper-spiked sediments.

Fourth instar Chironomus riparius larvae were exposed to four sediments spiked with copper. Length and copper concentration in the tissue were monitored daily. Kinetics data analysis was performed by fitting a one-compartment model. The analysis of growth data was performed using an energy-based approach which estimates a no-effect concentration (NEC). The elimination rate of copper did not depend on the sediment characteristics, whereas the bioconcentration factor differed by a factor of 10 among the tested sediments, accounting for differences in copper bioavailability. Consequently, the NEC expressed in term of exposure concentrations differed substantially between sediments. In contrast, the NEC expressed in terms of body residues did not depend on the sediment characteristics. This work links, for the first time, a mechanistic effects model with the critical body residue approach, and could contribute to develop relevant tools for sediment risk assessment.