Impact of genomic testing and patient-reported outcomes on receipt of adjuvant chemotherapy

Practice guidelines incorporate genomic tumor profiling, using results such as the Oncotype DX Recurrence Score (RS), to refine recurrence risk estimates for the large proportion of breast cancer patients with early-stage, estrogen receptor-positive disease. We sought to understand the impact of receiving genomic recurrence risk estimates on breast cancer patients’ well-being and the impact of these patient-reported outcomes on receipt of adjuvant chemotherapy. Participants were 193 women (mean age 57) newly diagnosed with early-stage breast cancer. Women were interviewed before and 2–3 weeks after receiving the RS result between 2011 and 2015. We assessed subsequent receipt of chemotherapy from chart review. After receiving their RS, perceived pros (t = 4.27, P < .001) and cons (t = 8.54, P <.001) of chemotherapy increased from pre-test to post-test, while perceived risk of breast cancer recurrence decreased (t = 2.90, P = .004). Women with high RS tumors were more likely to receive chemotherapy than women with low RS tumors (88 vs. 5 %, OR 0.01, 0.00–0.02, P < .001). Higher distress (OR 2.19, 95 % CI 1.05–4.57, P < .05) and lower perceived cons of chemotherapy (OR 0.50, 95 % CI 0.26–0.97, P < .05) also predicted receipt of chemotherapy. Distressed patients who saw few downsides of chemotherapy received this treatment. Clinicians should consider these factors when discussing chemotherapy with breast cancer patients

Demographic, clinical, and service-use characteristics related to the clinician’s recommendation to transition from child to adult mental health services

Purpose: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS. Methods: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations. Results: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. Conclusion: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services

Cohort profile : demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe

Purpose: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. Participants: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. Findings to date: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be ‘markedly ill’, ‘severely ill’ or ‘among the most extremely ill’ by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. Future plans: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. Trial registration number: NCT03013595

Participatory projects and their impact on immigrants’ integration in France

International audienc

Phosphorylation-independent membrane relocalization of ezrin following association with Dbl in vivo

Ezrin, a widespread protein involved in cell migration, morphogenesis and cell adhesion, belongs to a large family of proteins known as ERM ( ezrin, radixin, moesin). These three closely related proteins are thought to function as linkers between plasma membrane and actin cytoskeleton and their function is regulated by the small GTP-binding protein Rho. It has been previously shown that the active form of radixin can bind in vitro to Dbl, a Rho-specific guanine nucleotide exchange factor, although an in vivo interaction has not yet been demonstrated. In this paper, we attempted to investigate whether ezrin can also associate with Dbl. We show here that Dbl protein can effectively bind both in vitro and in vivo to the N-terminal region ( amino acids 1 - 531) of a constitutively active mutant of ezrin and with the full-length molecule. We found that this binding is mediated by the Dbl pleckstrin homology domain, responsible for the proper subcellular localization of the Dbl protein. Moreover, we show that Dbl induces localization to the plasma membrane of both the active deletion mutant and the full-length ezrin proteins. Finally, we show that the relocalization of ezrin is independent of Dbl GEF activity. These results indicate that Dbl could induce translocation of ezrin to the plasma membrane through a mechanism that does not require ezrin C-terminus phosphorylation by Rho-associated kinases

Growth arrest-inducing genes are activated in Dbl-transformed mouse fibroblasts

The Dbl oncogene is a guanine nucleotide exchange factor for Rho GTPases and its activity has been linked to the regulation of gene transcription. Dbl oncogene expression in NIH3T3 cells leads to changes in morphological and proliferative properties of these cells, inducing a highly transformed phenotype. To gain insights into Dbl oncogene-induced transformation we compared gene expression profiles between Dbl oncogene-transformed and parental NIH3T3 cells by cDNA microarray. We found that Dbl oncogene expression is associated with gene expression modulation involving upregulation of 51 genes and downregulation of 49 genes. Five of the overexpressed genes identified are known to exert antiproliferative functions. Our observations suggest that the expression of Dbl oncogene in NIH3T3 may lead to the induction of genes associated with cell cycle arrest, possibly through the activation of stress-induced kinases

French Policies on Refugees' access to housing

This country research report focuses on housing solutions for refugees and beneficiaries of international protection status in France. It is delivered under the H2020 project MERGING—Integration for Migrants. The main aims of this report are:• Provide a synthesis of the main legal structures existing in France delineated by targets (all arrivals, newly arrivals, refugees, vulnerable groups),• Classify policies depending on their scope,• Present the main debates in public policies about access to housing and access to the rest of social rights,• Identify tools developed in public policies to fight discrimination,• Describe the main tendencies in public policies devoted to social inclusion for immigrants during the last 10 years approximately,• Summarize the main ideological changes experienced in the last 10 years.The basic time frame of the analysis covers the years 2015-2021, however, where necessary we refer to previous years (e.g., important articles that shaped the field, political decisions and policy changes).The approaches and definitions applied in this report are broad. Indeed, one of the objectives of WP2 is to gather enough knowledge to develop a good understanding about the realities of housing for migrants in Europe. This step will allow us to identify a specific target population for the project. Consequently, the focus is on people who were forced to leave their domestic country, having or not an official status, or an international protection. This includes asylum seekers, refugees, temporary protection, etc.The structure of this country report includes several key parts, the first of which is this introduction outlining a framework for further consideration and embedding it in the context of the MERGING project and its WP2. It is followed by a presentation of the main legal structures existing in France (legal texts, organizations and responsible actors), 2) a classification of policies based on their scope and 3) a presentation of the main debates related to access to housing and social rights. Particular attention will be paid to identify tools created to fight discrimination, as well as the main trends in public policies devoted to social inclusion for immigrants since 2011. The report will conclude on a synthesis on the most important ideological changes experienced in the last 10 years.The next sessions provide a brief overview of our methodology, followed by a presentation of the characteristics and specificities of the French context regarding migrants’ access to housing

Importers, Exporters and the Division of the Gains from Trade *

Abstract This paper examines the microstructure of import markets and the division of the gains from trade among consumers, importers and exporters. When exporters and importers transact through anonymous markets, double marginalization and business stealing among competing importers lead to lower profits. Trading parties can overcome these inefficiencies by investing in richer arrangements to ensure bilateral profit maximization that eliminates double marginalization and joint profit maximization that also internalizes business stealing. The introduction of endogenous microstructure of import markets in a trade model means that trade liberalization can increase the incentive to engage in joint profit maximization, thus raising the profits of exporters and importers at the expense of consumer welfare. Following the US-Colombia free trade agreement, US exporters that received tariff reductions were more likely to increase their average price, decrease their quantity exported and reduce the number of import partners. As predicted by the theory, this import market consolidation occurs for medium-sized US exporters, who increase their average tariff-inclusive price by as much as 6 per cent, leading to a shift in surplus from the liberalizing country to the exporting country