No all’anoressia sì alla ricerca : il taboo anoressia analisi di uno spot per raccontare una magrezza relazionale

En las últimas décadas, los trastornos alimentarios (DCA), en abundancia y severidad de condiciones patológicas, se impusieron para los medios de comunicación, no sólo para la atención del ámbito de los profesionales de la salud, sino también para la persona ordinaria. Este proyecto de investigación es parte de una tendencia más amplia, cuyo objetivo es investigar los componentes etiológicos, educativos y sociales relativos a los trastornos alimentarios. Indicadores epistemológicos que guían el enfoque de la investigación de los siguientes: aspectos de prevención y tratamiento de trastornos de la alimentación y la construcción del significado de los trastornos alimentarios en los nuevos medios, el papel de la publicidad en la comunicación de las enfermedades y las actitudes y comportamientos adolescentes. El trabajo pretende analizar, a través de grupos focales e insumos proporcionados por el análisis de una campaña de publicidad, opiniones y actitudes de los niños hacia la publicidad vinculada a la DCA. Los resultados muestran que el tabú de las enfermedades y el mantenimiento puede ser desplegado y comunicado a través de la investigación, lo que le permite adquirir la perspectiva en supuestos de la juventud.In recent decades, eating disorders (DCA), in abundance and severity of pathological conditions, were imposed for the media, not only for the attention of the scope of health professionals, but also the ordinary person. This research project is part of a broader trend, which aims to investigate the etiological components, educational and social relating to eating disorders. Epistemological indicators that guide the research focus of the following: aspects of prevention and treatment of eating disorders and the construction of the meaning of eating disorders on the new media, the role of advertising in the communication of the disease and attitudes and behaviors adolescents. The work aims to analyze, through focus groups and inputs provided by the analysis of a publicity campaign, opinions and attitudes of children towards advertising tied to the DCA. The results show that the taboo of the diseases and maintenance can be deployed and communicated through research, allowing it to acquire the perspective view on assumptions of youth.Negli ultimi decenni i Disturbi del Comportamento Alimentare (DCA), per numerosità e gravità dei quadri clinici, si sono imposti, per opera dei media, non solo all’attenzione dei professionisti dell’ambito sanitario, ma anche della persona comune. Il presente progetto di ricerca si inserisce all’interno di un filone più ampio, volto ad indagare le componenti eziologiche, educative e sociali concernenti i disturbi del comportamento alimentare. Gli indicatori epistemologici che orientano la ricerca mettono a fuoco i seguenti elementi: gli aspetti della prevenzione e della terapia dei disturbi alimentari; la costruzione del significato dei disturbi alimentari attraverso i nuovi media; il ruolo della pubblicità nella comunicazione della malattia e negli atteggiamenti e comportamenti degli adolescenti. Il lavoro vuole analizzare, attraverso focus group e stimoli forniti dall’analisi di una campagna pubblicitaria, le opinioni e gli atteggiamenti dei ragazzi nei confronti della pubblicità legata ai DCA. I risultati evidenziano che il taboo delle malattie alimentari può e deve essere dispiegato e comunicato attraverso la ricerca, permettendo così di acquisire la visione prospettata dagli assunti del mondo giovanile.peerReviewe

Reduced platelet glycoprotein Ibα shedding accelerates thrombopoiesis and COX-1 recovery: implications for aspirin dosing regimen

Cardiovascular (CV) disease prevention with low-dose aspirin can be less effective in patients with a faster recovery of platelet (PLT) cyclooxygenase (COX)-1 activity during the 24-hour dosing interval. We previously showed that incomplete suppression of TXA2 over 24 hours can be rescued by a twice daily aspirin regimen. Here we show that reduced PLT glycoprotein (GP)Ibα shedding characterizes patients with accelerated COX-1 recovery and may contribute to higher thrombopoietin (TPO) production and higher rates of newly formed PLT, escaping aspirin inhibition over 24 hours. Two hundred aspirin-treated patients with high CV risk (100 with type 2 diabetes mellitus) were stratified according to the kinetics of PLT COX-1 activity recovery during the 10- to 24-hour dosing interval. Whole proteome analysis showed that PLT from patients with accelerated COX-1 recovery were enriched in proteins involved in cell survival, inhibition of apoptosis and cellular protrusion formation. In agreement, we documented increased plasma TPO, megakaryocyte maturation and proplatelet formation, and conversely increased PLT galactose and reduced caspase 3, phosphatidylserine exposure and ADAM17 activation, translating into diminished GPIbα cleavage and glycocalicin (GC) release. Treatment of HepG2 cells with recombinant GC led to a dose-dependent reduction of TPO mRNA in the liver, suggesting that reduced GPIbα ectodomain shedding may unleash thrombopoiesis. A cluster of clinical markers, including younger age, non-alcoholic fatty liver disease, visceral obesity and higher TPO/GC ratio, predicted with significant accuracy the likelihood of faster COX-1 recovery and suboptimal aspirin response. Circulating TPO/GC ratio, reflecting a dysregulation of PLT lifespan and production, may provide a simple tool to identify patients amenable to more frequent aspirin daily dosing

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

No all’anoressia sì alla ricerca : il taboo anoressia analisi di uno spot per raccontare una magrezza relazionale

En las últimas décadas, los trastornos alimentarios (DCA), en abundancia y severidad de condiciones patológicas, se impusieron para los medios de comunicación, no sólo para la atención del ámbito de los profesionales de la salud, sino también para la persona ordinaria. Este proyecto de investigación es parte de una tendencia más amplia, cuyo objetivo es investigar los componentes etiológicos, educativos y sociales relativos a los trastornos alimentarios. Indicadores epistemológicos que guían el enfoque de la investigación de los siguientes: aspectos de prevención y tratamiento de trastornos de la alimentación y la construcción del significado de los trastornos alimentarios en los nuevos medios, el papel de la publicidad en la comunicación de las enfermedades y las actitudes y comportamientos adolescentes. El trabajo pretende analizar, a través de grupos focales e insumos proporcionados por el análisis de una campaña de publicidad, opiniones y actitudes de los niños hacia la publicidad vinculada a la DCA. Los resultados muestran que el tabú de las enfermedades y el mantenimiento puede ser desplegado y comunicado a través de la investigación, lo que le permite adquirir la perspectiva en supuestos de la juventud.In recent decades, eating disorders (DCA), in abundance and severity of pathological conditions, were imposed for the media, not only for the attention of the scope of health professionals, but also the ordinary person. This research project is part of a broader trend, which aims to investigate the etiological components, educational and social relating to eating disorders. Epistemological indicators that guide the research focus of the following: aspects of prevention and treatment of eating disorders and the construction of the meaning of eating disorders on the new media, the role of advertising in the communication of the disease and attitudes and behaviors adolescents. The work aims to analyze, through focus groups and inputs provided by the analysis of a publicity campaign, opinions and attitudes of children towards advertising tied to the DCA. The results show that the taboo of the diseases and maintenance can be deployed and communicated through research, allowing it to acquire the perspective view on assumptions of youth.Negli ultimi decenni i Disturbi del Comportamento Alimentare (DCA), per numerosità e gravità dei quadri clinici, si sono imposti, per opera dei media, non solo all’attenzione dei professionisti dell’ambito sanitario, ma anche della persona comune. Il presente progetto di ricerca si inserisce all’interno di un filone più ampio, volto ad indagare le componenti eziologiche, educative e sociali concernenti i disturbi del comportamento alimentare. Gli indicatori epistemologici che orientano la ricerca mettono a fuoco i seguenti elementi: gli aspetti della prevenzione e della terapia dei disturbi alimentari; la costruzione del significato dei disturbi alimentari attraverso i nuovi media; il ruolo della pubblicità nella comunicazione della malattia e negli atteggiamenti e comportamenti degli adolescenti. Il lavoro vuole analizzare, attraverso focus group e stimoli forniti dall’analisi di una campagna pubblicitaria, le opinioni e gli atteggiamenti dei ragazzi nei confronti della pubblicità legata ai DCA. I risultati evidenziano che il taboo delle malattie alimentari può e deve essere dispiegato e comunicato attraverso la ricerca, permettendo così di acquisire la visione prospettata dagli assunti del mondo giovanile.peerReviewe

Lentiviral gene therapy for X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells(1,2). We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34(+) hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4-1.8 copies per neutrophil) and the persistence of 16-46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients

Lentiviral gene therapy for X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells1,2. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4-1.8 copies per neutrophil) and the persistence of 16-46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients

Evaluating risk, safety and efficacy of novel reproductive techniques and therapies through the EuroGTP II risk assessment tool

STUDY QUESTION Can risks associated with novelties in assisted reproduction technologies (ARTs) be assessed in a systematic and structured way? SUMMARY ANSWER An ART-specific risk assessment tool has been developed to assess the risks associated with the development of novelties in ART (EuroGTP II-ART). WHAT IS KNOWN ALREADY How to implement new technologies in ART is well-described in the literature. The successive steps should include testing in animal models, executing pre-clinical studies using supernumerary gametes or embryos, prospective clinical trials and finally, short- and long-term follow-up studies on the health of the offspring. A framework categorizing treatments from experimental through innovative to established according to the extent of the studies conducted has been devised. However, a systematic and standardized methodology to facilitate risk evaluation before innovations are performed in a clinical setting is lacking. STUDY DESIGN, SIZE, DURATION The EuroGTP II-ART risk assessment tool was developed on the basis of a generic risk assessment algorithm developed for tissue and cell therapies and products (TCTPs) in the context of the project 'Good Practices for demonstrating safety and quality through recipient follow-up European Good Tissue and cells Practices II (EuroGTP II)'. For this purpose, a series of four meetings was held in which eight ART experts participated. In addition, several tests and simulations were undertaken to fine-tune the final tool. PARTICIPANTS/MATERIALS, SETTING, METHODS The three steps comprising the EuroGTP II methodology were evaluated against its usefulness and applicability in ART. Ways to improve and adapt the methodology into ART risk assessment were agreed and implemented. MAIN RESULTS AND THE ROLE OF CHANCE Assessment of the novelty (Step 1), consisting of seven questions, is the same as for other TCTPs. Practical examples were included for better understanding. Identification of potential risks and consequences (Step 2), consisting of a series of risks and risk consequences to consider during risk assessment, was adapted from the generic methodology, adding more potential risks for processes involving gonadic tissues. The algorithm to score risks was also adapted, giving a specific range of highest possible risk scores. A list of strategies for risk reduction and definition of extended studies required to ensure effectiveness and safety (Step 3) was also produced by the ART experts, based on generic EuroGTP II methodology. Several explanations and examples were provided for each of the steps for better understanding within this field. LIMITATIONS, REASONS FOR CAUTION A multidisciplinary team is needed to perform risk assessment, to interpret results and to determine risk mitigation strategies and/or next steps required to ensure the safety in the clinical use of novelties. WIDER IMPLICATIONS OF THE FINDINGS This is a dynamic tool whose value goes beyond assessment of risk before implementing a novel ART in clinical practice, to re-evaluate risks based on information collected during the process

. Evaluating risk, safety and efficacy of novel reproductive techniques and therapies through the EuroGTP II risk assessment tool.

Study question: Can risks associated with novelties in assisted reproduction technologies (ARTs) be assessed in a systematic and structured way? Summary answer: An ART-specific risk assessment tool has been developed to assess the risks associated with the development of novelties in ART (EuroGTP II-ART). What is known already: How to implement new technologies in ART is well-described in the literature. The successive steps should include testing in animal models, executing pre-clinical studies using supernumerary gametes or embryos, prospective clinical trials and finally, short- and long-term follow-up studies on the health of the offspring. A framework categorizing treatments from experimental through innovative to established according to the extent of the studies conducted has been devised. However, a systematic and standardized methodology to facilitate risk evaluation before innovations are performed in a clinical setting is lacking. Study design, size, duration: The EuroGTP II-ART risk assessment tool was developed on the basis of a generic risk assessment algorithm developed for tissue and cell therapies and products (TCTPs) in the context of the project 'Good Practices for demonstrating safety and quality through recipient follow-up European Good Tissue and cells Practices II (EuroGTP II)'. For this purpose, a series of four meetings was held in which eight ART experts participated. In addition, several tests and simulations were undertaken to fine-tune the final tool. Participants/materials, setting, methods: The three steps comprising the EuroGTP II methodology were evaluated against its usefulness and applicability in ART. Ways to improve and adapt the methodology into ART risk assessment were agreed and implemented. Main results and the role of chance: Assessment of the novelty (Step 1), consisting of seven questions, is the same as for other TCTPs. Practical examples were included for better understanding. Identification of potential risks and consequences (Step 2), consisting of a series of risks and risk consequences to consider during risk assessment, was adapted from the generic methodology, adding more potential risks for processes involving gonadic tissues. The algorithm to score risks was also adapted, giving a specific range of highest possible risk scores. A list of strategies for risk reduction and definition of extended studies required to ensure effectiveness and safety (Step 3) was also produced by the ART experts, based on generic EuroGTP II methodology. Several explanations and examples were provided for each of the steps for better understanding within this field. Limitations, reasons for caution: A multidisciplinary team is needed to perform risk assessment, to interpret results and to determine risk mitigation strategies and/or next steps required to ensure the safety in the clinical use of novelties. Wider implications of the findings: This is a dynamic tool whose value goes beyond assessment of risk before implementing a novel ART in clinical practice, to re-evaluate risks based on information collected during the process. Study funding / competing interest(s): This study was called EUROGTP II and was funded by the European Commission (Grant agreement number 709567). The authors declare no competing interests concerning the results of this study