Documento final : políticas regionales de innovación en el MERCOSUR; obstáculos y oportunidades

El MERCOSUR puede ser visto como una institución estratégica en términos de desarrollo, principalmente dada su potencialidad para la generación de sinergias y complementariedades en el plano productivo, científico y tecnológico. En este sentido, el presente documento busca contribuir con un análisis del estado de situación en la región, la identificación de especificidades y complementariedades y el desarrollo, presentación y discusión de una propuesta de política regional de innovación. Se evidencia una fuerte necesidad de coordinar las acciones nacionales en un plano regional e internacional y la existencia de sectores estratégicos, con fuertes potencialidades, que demandan de acciones concretas en el corto y mediano plazo si se pretende maximizar su impacto en el bienestar social

Active study: undetected prevalence and clinical inertia in the treatment of breakthrough cancer pain (BTcP)

Aims To prove if there is clinical inertia in the identification and treatment of episodes of breakthrough cancer pain (BTcP), comparing actual results from clinical practice with clinical oncologists’ prior perception. Design Observational and descriptive study, using information collected by practising medical oncologists, at three moments: (a) questionnaire regarding their professional judgement of the handling of patients with BTcP in their practice, (b) cross-sectional clinical screening, to detect possible existing cases of BTcP in a representative sample of their patients, (c) retrospective self-audit of clinical case histories of patients diagnosed with BTcP to find out about how it has been handled. Participants and study period A random sample on a state level of 108 specialists in medical oncology. 540 patients who suffer some type of cancer pain on the designated study date for each specialist (July–December 2016). Results The global prevalence of BTcP in the study sample covered 91.3% of the patients who were suffering some type of cancer pain. Barely 2% of the doctors surveyed suspected figures around this mark. 40.9% of the cases had not been previously detected as BTcP by their doctors. Although 90% of the patients who had previously been diagnosed with BTcP received a specific analgesic treatment for the symptoms, 42% of those patients with known BTcP were not able to control their episodes of pain. Conclusions Clinical inertia is a serious problem in the handling of BTcP in medical oncology services, where it is the subject of a significantly low level of detection and treatment, despite the contrasting perception of specialists.pre-print339 K

ATENDIMENTO AO ADOLESCENTE USUÁRIO DE SUBSTÂNCIAS PSICOATIVAS: PAPEL DO CENTRO DE ATENÇÃO PSICOSSOCIAL

The present study aimed to gain insight into the role of a Psychosocial Care Center for Users of Alcohol and other Drugs (CAPS AD) that assists adolescents who usepsychoactive substances, from the views of the professionals of Guardianship Councils and the Judiciary. Qualitative researchconductedfrom June to August 2015, in units of a Psychosocial Care Network (RAPS) for adolescents, in a city of the state of Rio Grande do Sul, based on semi-structured interviews with 13 professionals from Social Work and the Judiciary. Two categories emerged from data analysis: The role of the Psychosocial Care Center Alcohol and other Drugsand Challengesfaced bythe CAPS professionals regarding the delivery of care who use alcohol and other drugs.O estudo teve como objetivo conhecer o papel de um Centro de Atenção Psicossocial Álcool e Outras Drogas no atendimento ao adolescente usuário de substâncias psicoativas, na perspectiva dos profissionais que atuam no conselho tutelar e no judiciário. Pesquisa qualitativa, realizada entre junho e agosto de 2015, em serviços da Rede de Atenção Psicossocial ao adolescente, em um município do estado do Rio Grande do Sul, a partir de entrevistas semiestruturadas com 13 profissionais da Assistência Social e do Judiciário. Após análise dos dados, emergiram duas categorias: O papel do Centro de Atenção Psicossocial Álcool e outras drogas; e, Desafios no atendimento prestado aos adolescentes pelo Centro de Atenção Psicossocial Álcool e outras drogas. Conclui-se que há necessidade das intervenções realizadas com adolescentes usuários estarem pautadas na perspectiva interdisciplinar, intersetorial e com profissionais qualificados, a fim de potencializar as ações de atenção à saúde para atender essa demanda.Estudio cuyo objetivo fue conocer el papel de un Centro de Atención Psicosocial de Álcohol y Otras Drogas en el atendimiento al adolescente usuario de sustancias psicoactivas, bajo la perspectiva de los profesionales que actuan en el consejo tutelar y en el judiciario. Investigación cualitativa, realizada entre junio y agosto de 2015, en servicios de la Red de Atención Psicosocial al adolescente, en un município del estado de Rio Grande do Sul, con base en entrevistas semiestructuradas a 13 profesionales de la Asistencia Social y del Judiciario. Resultaron dos categorias del análisis de los datos: el papel de la Atención Psicosocial de Álcohol y Otras Drogas; y, Desafíos en el atendimiento prestado a los adolescentes por la Atención Psicosocial de Álcohol y Otras Drogas. Se concluye que hay necesidad de que las intervenciones realizadas con adolescentes usuarios estén pautadas en la perspectiva interdisciplinar, intersectorial, además de la priorización por profesionales calificados, con fines de potencializar las acciones de atención a la salud para atender a esa demanda

Identification and neuromodulation of brain states to promote recovery of consciousness

Experimental and clinical studies of consciousness identify brain states (i.e., transient, relevant features of the brain associated with the state of consciousness) in a non-systematic manner and largely independent from the research into the induction of state changes. In this narrative review with a focus on patients with a disorder of consciousness (DoC), we synthesize advances on the identification of brain states associated with consciousness in animal models and physiological (sleep), pharmacological (anesthesia) and pathological (DoC) states of altered consciousness in human. We show that in reduced consciousness the frequencies in which the brain operates are slowed down and that the pattern of functional communication in the brain is sparser, less efficient, and less complex. The results also highlight damaged resting state networks, in particular the default mode network, decreased connectivity in long-range connections and in the thalamocortical loops. Next, we show that therapeutic approaches to treat DoC, through pharmacology (e.g., amantadine, zolpidem), and (non-)invasive brain stimulation (e.g., transcranial current stimulation, deep brain stimulation) have shown some effectiveness to promote consciousness recovery. It seems that these deteriorated features of conscious brain states may improve in response to these neuromodulation approaches, yet, targeting often remains non-specific and does not always lead to (behavioral) improvements. Furthermore, in silico model-based approaches allow the development of personalized assessment of the effect of treatment on brain-wide dynamics. Although still in infancy, the fields of brain state identification and neuromodulation of brain states in relation to consciousness are showing fascinating developments that, when united, might propel the development of new and better targeted techniques for DoC. For example, brain states could be identified in a predictive setting, and the theoretical and empirical testing (i.e., in animals, under anesthesia and patients with a DoC) of neuromodulation techniques to promote consciousness could be investigated. This review further helps to identify where challenges and opportunities lay for the maturation of brain state research in the context of states of consciousness. Finally, it aids in recognizing possibilities and obstacles for the clinical translation of these diagnostic techniques and neuromodulation treatment options across both the multi-modal and multi-species approaches outlined throughout the review. This paper presents interactive figures, supported by the Live Paper initiative of the Human Brain Project, enabling the interaction with data and figures illustrating the concepts in the paper through EBRAINS (go to https://wiki.ebrains.eu/bin/view/Collabs/live-paper-states-altered-consciousness and get started with an EBRAINS account).NA is research fellow, OG is Research Associate, and SL is research director at FRS-FNRS. JA is postdoctoral fellow at the FWO. The study was further supported by the University and University Hospital of Liège, the BIAL Foundation, the Belgian National Funds for Scientific Research (FRS-FNRS), the European Union's Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), the FNRS PDR project (T.0134.21), the ERA-Net FLAG-ERA JTC2021 project ModelDXConsciousness (Human Brain Project Partnering Project), the fund Generet, the King Baudouin Foundation, the Télévie Foundation, the European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) in the framework of the PRODEX Programme, the Public Utility Foundation 'Université Européenne du Travail', "Fondazione Europea di Ricerca Biomedica", the BIAL Foundation, the Mind Science Foundation, the European Commission, the Fondation Leon Fredericq, the Mind-Care foundation, the DOCMA project (EU-H2020-MSCA–RISE–778234), the National Natural Science Foundation of China (Joint Research Project 81471100) and the European Foundation of Biomedical Research FERB Onlus

combined pik3ca and fgfr inhibition with alpelisib and infigratinib in patients with pik3ca mutant solid tumors with or without fgfr alterations

PURPOSE Concurrent PIK3CA mutations and fibroblast growth factor receptor (FGFR) alterations occur in multiple cancer types, including estrogen receptor–positive breast cancer, bladder cancer, and endometrial cancer. In this first-in-human combination trial, we explored safety and preliminary efficacy of combining the PI3Kα selective inhibitor alpelisib with the FGFR1-4 selective inhibitor infigratinib. PATIENTS AND METHODS Patients with PIK3CA-mutant advanced solid tumors, with or without FGFR1-3 alterations, were enrolled in the dose escalation or one of three molecular-defined dose-expansion cohorts. The primary end point was the maximum tolerated dose. Secondary end points included safety, pharmacokinetics, and response. Archival tumor samples were sequenced to explore genomic correlates of response. RESULTS In combination, both agents were escalated to full, single-agent recommended doses (alpelisib, 300 mg per day continuously; infigratinib, 125 mg per day 3 weeks on followed by 1 week off). The toxicity profile of the combination was consistent with the established safety profile of each agent, although 71% of all patients required at least one treatment interruption or dose reduction. Molecularly selected dose expansions in breast cancer and other solid tumors harboring PIK3CA mutations, alone or in combination with FGFR alterations, identified sporadic responses, predominately in tumor types and genotypes previously defined to have sensitivity to these agents. CONCLUSION The combination of alpelisib and infigratinib can be administered at full single-agent doses, although the high rate of dose interruption or reduction suggests long-term tolerability may be challenging. In exploratory signal-seeking cohorts of patients harboring dual PIK3CA and FGFR1-3 alterations, no clear evidence of synergistic activity was observed

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Correcting Mortality for Loss to Follow-Up: A Nomogram Applied to Antiretroviral Treatment Programmes in Sub-Saharan Africa

Matthias Egger and colleagues present a nomogram and a web-based calculator to correct estimates of program-level mortality for loss to follow-up, for use in antiretroviral treatment programs