Analysis of efficacy and safety of CAR T-cell therapy in relapsed/refractory lymphomas: current indications and future perspectives

In the last few years, the introduction of chimeric antigen receptor (CAR) T-cell therapy into clinical practice has revolutionized the approach to patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), whose outcome used to be dismal with median overall survival (OS) of approximately 6 months with standard salvage therapy. At our Institute, we started treating diffuse large B-cell lymphoma (DLBCL) patients with CAR T-cell products in August 2019 and they received either axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) as per regulatory indications. This research project presents the 2-year follow-up of the first 53 treated patients. Our first aim is to investigate the feasibility of this treatment strategy in a real-world setting, although the reimbursement criteria set by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) are very similar to the inclusion criteria of clinical trials and stricter than those established by the regulatory authorities of many foreign countries. One month after infusion, the ORR was 66% with 19 patients already in CR (38%). Restaging at 3, 6 and 12 months post-infusion shows that early CRs tend to be maintained over time and, moreover, that a considerable number of PRs and a few SDs can improve into a CR. The safety data were consistent with what is reported in the literature; toxicity was generally manageable, largely due to the increasing expertise in handling the specific adverse events related to CAR T-cell therapy. Our results confirms that CAR T-cell therapy is both safe and effective in a real-life setting and that it represents a crucial weapon in a subset of patients who were previously doomed to an inevitably severe prognosis.

GUI design for in-car message diagnosis

Electronics needs communication to serve the vehicular world, to let all ECUs to com- municate with each other are needed buses, each bus serves different stuffs and is able to communicate. In the evolution of automotive architecture, integration of multiple func- tionalities in a single ECU will be one of the key aspects. The analysis of in-vehicle data, both for diagnosis and study-case of a particular behaviour, is the basis for future’s technologies and applications. Starting from these ideas, the need of creating a correlation between the Vehicle state and the anomaly. In order to create a link among them, has been created an interface able to simplify the in-car diagnosis and creating a link among vehicle stateand anomaly, looking also to the study-case of the driver's behaviour.

VRSDE: implementazione di tecnologie AR e VR all'interno dei processi di Car Design. Caso Studio: Maserati Gran Turismo

Con il seguente elaborato ci si è posti come oggetto di ricerca il valutare e mostrare come l’implementazione delle nuove tecnologie di realtà virtuale e aumentata possano portare un miglioramento al metodo di studio e lavoro dello Stylistic Design Engineering nello sviluppo di un concept design di un nuovo veicolo. Si illustreranno i cambiamenti apportati dall’utilizzo di un software di modellazione in realtà virtuale lungo tutto il processo di sviluppo, mettendo in evidenza la grande potenzialità di poter essere un forte strumento di condivisione e integrazione in ogni fase del progetto di tutte le figure professionali coinvolte nello sviluppo del prodotto.

A new concept for a Sport-Coupè car developed with the Industrial Design Structure method (IDeS)

The aim of this study, conducted in collaboration with Lawrence Technological University in Detroit, is to create, through the method of the Industrial Design Structure (IDeS), a new concept for a sport-coupe car, based on a restyling of a retro model (Ford Mustang 1967). To date, vintage models of cars always arouse great interest both for the history behind them and for the classic and elegant style. Designing a model of a vehicle that can combine the charm of retro style with the innovation and comfort of modern cars would allow to meet the needs and desires of a large segment of the market that today is forced to choose between past and future. Thanks to a well-conceived concept car an automaker company is able to express its future policy, to make a statement of intent as, such a prototype, ticks all the boxes, from glamour and visual wow-factor to technical intrigue and design fascination. IDeS is an approach that makes use of many engineering tools to realize a study developed on several steps that must be meticulously organized and timed. With a deep analysis of the trends dominating the automotive industry it is possible to identify a series of product requirements using quality function deployment (QFD). The considerations from this first evaluation led to the definition of the technical specifications via benchmarking (BM) and top-flop analysis (TFA). Then, the structured methodology of stylistic design engineering (SDE) is applied through six phases: (1) stylistic trends analysis; (2) sketches; (3) 2D CAD drawings; (4) 3D CAD models; (5) virtual prototyping; (6) solid stylistic model. Finally, Developing the IDeS method up to the final stages of Prototypes and Testing you get a product as close as possible to the ideal vehicle conceptualized in the initial analysis.

Comparison Of Techniques For The Isolation Of Volatiles From Cashew Apple Juice.

The aim of this study was to compare the performance of the following techniques on the isolation of volatiles of importance for the aroma/flavor of fresh cashew apple juice: dynamic headspace analysis using PorapakQ(®) as trap, solvent extraction with and without further concentration of the isolate, and solid-phase microextraction (fiber DVB/CAR/PDMS). A total of 181 compounds were identified, from which 44 were esters, 20 terpenes, 19 alcohols, 17 hydrocarbons, 15 ketones, 14 aldehydes, among others. Sensory evaluation of the gas chromatography effluents revealed esters (n = 24) and terpenes (n = 10) as the most important aroma compounds. The four techniques were efficient in isolating esters, a chemical class of high impact in the cashew aroma/flavor. However, the dynamic headspace methodology produced an isolate in which the analytes were in greater concentration, which facilitates their identification (gas chromatography-mass spectrometry) and sensory evaluation in the chromatographic effluents. Solvent extraction (dichloromethane) without further concentration of the isolate was the most efficient methodology for the isolation of terpenes. Because these two techniques also isolated in greater concentration the volatiles from other chemical classes important to the cashew aroma, such as aldehydes and alcohols, they were considered the most advantageous for the study of cashew aroma/flavor.

Machado de assis's epilepsy

Machado de Assis (1839-1908) is considered the most important Brazilian writer and a great universal literary figure. Little is know about his medical, personal and family history. He hid his «disease» as much as possible. Machado referred to «strange things» having happened to him in his childhood. He described seizures as «nervous phenomena», «absenses», «my illness». Laet observed a seizure and described it as: «... when Machado approached us and spoke to me in disconnected words. I looked at him in surprise and found his features altered. Knowing that from time to time he had nervous problems,... and only permitted Machado take the Laranjeiras Street car, when I saw that he was completely well». A photographically documented seizure is shown. Alencar wrote, «The preoccupation with health was frequent: either he was having the consequences of a fit or was foreboding one». It is clear that Machado presented localized symptomatic epilepsy with complex partial seizures secondarily generalized of unknown etiology. The seizures which began in infancy or childhood had remission in adolescence and then recurred in his thirties and became more frequent in his later years. His depression got markedly worse with age. In our opinion, the greatest consequence of Machado's epilepsy, was his psychological suffering due to the prejudice of the times. Despite this Machado showed all his genius, which is still actual and universal.

Stress no trabalho em professores de educação fisica do sistema municipal de educação, na comunidade de Concepcion, oitava região, Chile

Universidade Estadual de Campinas. Faculdade de Educação Física

Juventude, lazer e uso abusivo de alcool

Universidade Estadual de Campinas . Faculdade de Educação Física

O risco espacial e fatores associados ao edentulismo em idosos em município do Sudeste do Brasil

Objetivou-se identificar fatores associados ao edentulismo e o seu risco espacial em idosos. Foi realizado um estudo transversal em uma amostra de 372 indivíduos de 60 anos e mais, no Município de Botucatu, São Paulo, Brasil, em 2005. Razões de prevalência brutas e ajustadas foram estimadas por meio de regressão de Poisson, com estimativa robusta da variância e procedimentos de modelagem hierárquica. A análise espacial foi realizada por estimativas de densidade de Kernel. A prevalência de edentulismo foi de 63,17%. Os fatores sociodemográficos associados ao edentulismo foram a baixa escolaridade, o aumento do número de pessoas por cômodo, não possuir automóvel e idade mais avançada, presença de comorbidades, ausência de um cirurgião-dentista regular e ter realizado a última consulta há três anos ou mais. A análise espacial mostrou maior risco nas áreas periféricas. Obteve-se uma melhor compreensão da perda dentária entre os idosos, subsidiando o planejamento de ações em saúde coletiva.

Association of dental enamel lead levels with risk factors for environmental exposure

OBJECTIVE: To analyze household risk factors associated with high lead levels in surface dental enamel. METHODS: A cross-sectional study was conducted with 160 Brazilian adolescents aged 14-18 years living in poor neighborhoods in the city of Bauru, southeastern Brazil, from August to December 2008. Body lead concentrations were assessed in surface dental enamel acid-etch microbiopsies. Dental enamel lead levels were measured by graphite furnace atomic absorption spectrometry and phosphorus levels were measured by inductively coupled plasma optical emission spectrometry. The parents answered a questionnaire about their children's potential early (05 years old) exposure to well-known lead sources. Logistic regression was used to identify associations between dental enamel lead levels and each environmental risk factor studied. Social and familial covariables were included in the models. RESULTS: The results suggest that the adolescents studied were exposed to lead sources during their first years of life. Risk factors associated with high dental enamel lead levels were living in or close to a contaminated area (OR = 4.49; 95% CI: 1.69;11.97); and member of the household worked in the manufacturing of paints, paint pigments, ceramics or batteries (OR = 3.43; 95% CI: 1.31;9.00). Home-based use of lead-glazed ceramics, low-quality pirated toys, anticorrosive paint on gates and/or sale of used car batteries (OR = 1.31; 95% CI: 0.56;3.03) and smoking (OR = 1.66; 95% CI: 0.52;5.28) were not found to be associated with high dental enamel lead levels. CONCLUSIONS: Surface dental enamel can be used as a marker of past environmental exposure to lead and lead concentrations detected are associated to well-known sources of lead contamination.

Acessibilidade aos serviços de saúde por pessoas com deficiência

OBJETIVO: Analisar as dificuldades de acessibilidade aos serviços de saúde vividas por pessoas com deficiência. PROCEDIMENTOS METODOLÓGICOS: Estudo qualitativo realizado com pessoas que relataram ter algum tipo de deficiência (paralisia ou amputação de membros; baixa visão, cegueira unilateral ou total; baixa audição, surdez unilateral ou total). Foram entrevistados 25 indivíduos (14 mulheres) na cidade de São Paulo, SP, de junho a agosto de 2007, que responderam perguntas referentes a deslocamento e acessibilidade aos serviços de saúde. A metodologia utilizada para análise foi o discurso do sujeito coletivo e as análises foram conduzidas com recurso do programa Qualiquantisoft. ANÁLISE DOS RESULTADOS: A análise dos discursos sobre o deslocamento ao serviço de saúde mostrou diversidade quanto ao usuário ir ao serviço sozinho ou acompanhado, utilizar carro particular, transporte coletivo, ir a pé ou de ambulância e demandar tempo variado para chegar ao serviço. Com relação às dificuldades oferecidas de acessibilidade pelos serviços de saúde, houve relatos de demora no atendimento, problemas com estacionamento, falta de rampas, elevadores, cadeiras de rodas, sanitários adaptados e de médicos. CONCLUSÕES: As pessoas com algum tipo de deficiência fizeram uso de meios de transporte diversificados, necessitando de companhia em alguns casos. Problemas na acessibilidade dos serviços de saúde foram relatados pelos sujeitos com deficiências, contrariando o princípio da eqüidade, preceito do Sistema Único de Saúde.

Inatividade física e fatores associados em adultos, São Paulo, Brasil

OBJETIVO: Analisar prevalências de inatividade física e fatores associados, e exercícios e esportes praticados segundo escolaridade em 2.050 adultos de 18 a 59 anos de idade - Estado de São Paulo, Brasil. MÉTODOS: Estudo transversal de base populacional com amostra estratificada e em múltiplos estágios. A inatividade física global foi aferida pelo International Physical Activity questionary - IPAQ short version, e por questão sobre prática regular de atividade física no lazer. A análise dos dados levou em conta o desenho amostral. RESULTADOS: A prevalência de inatividade física no lazer foi maior entre as mulheres. Já a inatividade física pelo IPAQ foi maior entre os homens. Modelos de regressão múltipla de Poisson indicaram, nos homens, menor inatividade física pelo IPAQ nos solteiros e separados, estudantes e aqueles que não possuíam carro. A inatividade física no lazer foi maior nos homens acima de 40 anos e com menor escolaridade ou apenas estudantes. A inatividade física pelo IPAQ, nas mulheres, foi mais prevalente entre as com maior escolaridade, ocupações menos qualificadas e viúvas; a inatividade física no lazer diminuiu com o aumento da idade e da escolaridade. Entre as modalidades praticadas no lazer, a caminhada foi a mais prevalente nas mulheres e o futebol nos homens. A maioria das modalidades foi diretamente associada à escolaridade; aproximadamente 25% dos indivíduos com mais de 12 anos de estudo praticava caminhada. CONCLUSÕES: Estes resultados sugerem que intervenções e políticas públicas de promoção da atividade física devem considerar diferenças socioeconômicas, de gênero, bem como as modalidades e o contexto em que a atividade física é praticadA

A questão social na França contemporânea: uma experiência de pesquisa

A França passou por conflitos urbanos em seus bairros populares. Incidentes com a polícia marcados pela morte de um morador, geralmente jovem ou adolescente, são seguidos por manifestações violentas: quebra-quebras, incêndios de carros e/ou estabelecimentos públicos e privados, enfrentamentos com a polícia. Nos conflitos da "banlieue" francesa podem ser percebidos elementos comuns a eventos ingleses e/ou americanos de outras décadas.OBJETIVO: consiste em identificar a percepção e as representações de moradores sobre suas condições de vida e saúde na França.MÉTODO: pesquisa qualitativa realizada em Les Aubiers, bairro popular de Bordeaux, nos anos de 2002 e 2005. A população de moradores desse bairro e é composta principalmente por imigrantes ou fanceses de origem estrangeira, provenientes de diferentes locais: África do Norte, África Sub-Sahariana, Turquia, Portugal , Ilha de Reunião. Os indicadores sociais e econômicos apresentam níveis significativamente mais baixos do que os de outros bairros de Bordeaux, acompanhando as tendências encontradas nas outras "banlieues". Entre esses indicadores, a taxa de desemprego, principalmente entre jovens, é alarmante (40 por cento).RESULTADOS E DISCUSSÃO: as políticas sociais deveriam ser mais voltadas para os indivíduos do que para o território, pois este só poderá ser transformado pelos primeiros e não o contrário. Um bairro e uma população estigmatizados, estão contemplados por uma ampla política social. Ainda que passível de crítica, não se pode ignorar a existência de esforços sistematicos de integração, nem a existência de políticas sociais. Se elas são inadequadas, trata-se de ampliar o espaço de discusão para sua reforma. Trata-se de saber qual a disposição das sociedades contemporâneas, como um todo, para lutar contra as inequidades e segregações

Adherence to cervical and breast cancer programs is crucial to improving screening performance

Introduction: Cervical and breast cancer are the most common malignancies among women worldwide. Effective screening can facilitate early detection and dramatically reduce mortality rates. The interface between those screening patients and patients most needing screening is complex, and women in remote areas of rural counties face additional barriers that limit the effectiveness of cancer prevention programs. This study compared various methods to improve compliance with mass screening for breast and cervical cancer among women in a remote, rural region of Brazil. Methods: In 2003, a mobile unit was used to perform 10 156 mammograms and Papanicolaou smear tests for women living in the Barretos County region of Sao Paulo state, Brazil (consisting of 19 neighbouring cities). To reach the women, the following community outreach strategies were used: distribution of flyers and pamphlets; media broadcasts (via radio and car loudspeakers); and community healthcare agents (CHCAs) making home visits. Results: The most useful intervention appeared to be the home visits by healthcare agents or CHCAs. These agents of the Family Health Programme of the Brazilian Ministry of Health reached an average of 45.6% of those screened, with radio advertisements reaching a further 11.9%. The great majority of the screened women were illiterate or had elementary level schooling (80.9%) and were of 'poor' or 'very poor' socioeconomic class (67.2%). Conclusions: Use of a mobile screening unit is a useful strategy in developing countries where local health systems have inadequate facilities for cancer screening in underserved populations. A multimodal approach to community outreach strategies, especially using CHCAs and radio advertisements, can improve the uptake of mass screening in low-income, low-educational background female populations.

H alpha spectropolarimetry of the B[e] supergiant GG Carinae

Aims. We study the geometry of the circumstellar environment of the B[e] supergiant star GG Car. Methods. We present observations acquired using the IAGPOL imaging polarimeter in combination with the Eucalyptus-IFU spectrograph to obtain spectropolarimetric measurements of GG Car across Ha at two epochs. Polarization effects along the emission line are analysed using the Q-U diagram. In particular, the polarization position angle (PA) obtained using the line effect is able to constrain the symmetry axis of the disk/envelope. Results. By analysing the fluxes, GG Car shows an increase in its double-peaked Ha line emission relative to the continuum within the interval of our measurements (similar to 43 days). The depolarization line effect around Ha is evident in the Q-U diagram for both epochs, confirming that light from the system is intrinsically polarized. A rotation of the PA along Ha is also observed, indicating a counter-clockwise rotating disk. The intrinsic PA calculated using the line effect (similar to 85 degrees.) is consistent between our two epochs, suggesting a clearly defined symmetry axis of the disk.