Who are the women who enrolled in the POSITIVE trial: a global study to support young hormone receptor positive breast cancer survivors desiring pregnancy

Background: Premenopausal women with early hormone-receptor positive (HR+) breast cancer receive 5-10 years of adjuvant endocrine therapy (ET) during which pregnancy is contraindicated and fertility may wane. The POSITIVE study investigates the impact of temporary ET interruption to allow pregnancy. Methods: POSITIVE enrolled women with stage I-III HR + early breast cancer, <42 years, who had received 18-30 months of adjuvant ET and wished to interrupt ET for pregnancy. Treatment interruption for up to 2 years was permitted to allow pregnancy, delivery and breastfeeding, followed by ET resumption to complete the planned duration. Findings: From 12/2014 to 12/2019, 518 women were enrolled at 116 institutions/20 countries/4 continents. At enrolment, the median age was 37 years and 74.9 % were nulliparous. Fertility preservation was used by 51.5 % of women. 93.2 % of patients had stage I/II disease, 66.0 % were node-negative, 54.7 % had breast conserving surgery, 61.9 % had received neo/adjuvant chemotherapy. Tamoxifen alone was the most prescribed ET (41.8 %), followed by tamoxifen + ovarian function suppression (OFS) (35.4 %). A greater proportion of North American women were <35 years at enrolment (42.7 %), had mastectomy (59.0 %) and received tamoxifen alone (59.8 %). More Asian women were nulliparous (81.0 %), had node negative disease (76.2%) and received tamoxifen + OFS (56.0 %). More European women had received chemotherapy (69.3 %). Interpretation: The characteristics of participants in the POSITIVE study provide insights to which patients and doctors considered it acceptable to interrupt ET to pursue pregnancy. Similarities and variations from a regional, sociodemographic, disease and treatment standpoint suggest specific sociocultural attitudes across the world. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The link between copper and Wilson’s disease

Wilson’s disease (hepatolenticular degeneration) is a rare inherited autosomal recessive disorder of copper metabolism leading to copper accumulation in the liver and extrahepatic organs such as the brain and cornea. Patients may present with combinations of hepatic, neurological and psychiatric symptoms. Copper is the therapeutic target for the treatment of Wilson’s disease. But how did copper come to be linked with Wilson’s disease? The answer encompasses a study of enzootic neonatal ataxia in lambs in the 1930s, the copper-chelating properties of British Anti-Lewisite, and the chemical analysis for copper of the organs of deceased Wilson’s disease patients in the mid-to-late 1940s. Wilson’s disease is one of a number of copper-related disorders where loss of copper homeostasis as a result of genetic, nutritional or environmental factors affects human health

A framework for understanding cumulative impacts, supporting environmental decisions and informing resilience based management of the Great Barrier Reef World Heritage Area: Final Report to the Great Barrier Reef Marine Park Authority and Department of the Environment

This project was commissioned by and developed with the Department of the Environment and the Great Barrier Reef Marine Park Authority (GBRMPA) to develop a qualitative framework for understanding cumulative impacts on the resilience of coral reef and seagrass ecosystems to inform decision making in the Great Barrier Reef World Heritage Area (GBRWHA). This report is the result of close collaboration between the Australian Institute of Marine Science (AIMS), GBRMPA, Department of the Environment, the Commonwealth Scientific and Industrial Research Organisation (CSIRO) and the University of Melbourne. The Great Barrier Reef is facing a range of pressures, and supporting the resilience of the Reef has become a central focus in its management. A key challenge for managers is to understand the cumulative impacts of multiple stressors and incorporating this knowledge into management decisions. The Cumulative Impact and Structured Decision-Making (CISDM) framework represented in this report is designed to assist Great Barrier Reef Marine Park managers and stakeholders in this challenge. The framework uses qualitative and probabilistic modelling to provide a systems-level understanding of how cumulative stressors affect coral reefs and seagrass ecosystems in the GBRWHA. These ecosystems underpin matters of national environmental significance (MNES), including the outstanding universal value (OUV) of the GBRWHA. This report forms one part of the department's program of work funded under the Sustainable Regional Development Program to support the Strategic Assessment of the Great Barrier Reef World Heritage Area.This record includes 2 *.NETA files as mentioned in the report on page 38. These files are specific to an application called Netica. Please see https://www.norsys.com/netica.html for more information