Neural correlates and neural computations in posterior parietal cortex during perceptual decision-making

A recent line of work has found remarkable success in relating perceptual decision-making and the spiking activity in the macaque lateral intraparietal area (LIP). In this review, we focus on questions about the neural computations in LIP that are not answered by demonstrations of neural correlates of psychological processes. We highlight three areas of limitations in our current understanding of the precise neural computations that might underlie neural correlates of decisions: (1) empirical questions not yet answered by existing data; (2) implementation issues related to how neural circuits could actually implement the mechanisms suggested by both extracellular neurophysiology and psychophysics; and (3) ecological constraints related to the use of well-controlled laboratory tasks and whether they provide an accurate window on sensorimotor computation. These issues motivate the adoption of a more general “encoding-decoding framework” that will be fruitful for more detailed contemplation of how neural computations in LIP relate to the formation of perceptual decisions

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival

Perfis visíveis na gestão social do desenvolvimento Visible profiles in the social management of development

Este artigo estuda a relação existente entre a gestão social do desenvolvimento, a performance de organizações da sociedade civil e o perfil de seus líderes. Para tanto, foram realizadas duas entrevistas, por meio da técnica da história oral, com dois gestores fundadores das respectivas organizações onde trabalham, situadas em Salvador e consideradas de reputação. Algumas questões nortearam o estudo qualitativo. Como a história de vida do seu principal gestor contribuiu para a organização ser o que é hoje? Como a sua história de vida se confunde com a história da organização? O que o levou a ser um gestor social e, mais especificamente, a fundar a organização? O que se vislumbra para o futuro da organização? Conclui-se que as organizações e seus gestores estão estreitamente imbricados e o sucesso das organizações reflete a trajetória bem-sucedida de seus líderes.<br>This article studies the relations between the social management of development, the performance of civil society organizations and their leaders' profile. For that purpose two interviews using oral history technique were carried out with two CEOs who founded their respective well-reputed organizations in the Brazilian city of Salvador. The following issues guided the qualitative study: To what extent did CEO's life history contribute to the present status of the organization? In what sense is his life history tied with the history of the organization? What turned him into a social manager, and, more particularly, what led him to found the organization? What are the expectations concerning the future of the organization? Conclusions point out that organizations and their managers are intimately imbricated, and that the success of organizations reflects the successful life history of their leaders