Front-line chemo-immunotherapy is not inferior to ibrutinib in CLL

International audienc

Time from diagnosis to institutionalization and death in people with dementia.

Introduction Reliable estimates of time from diagnosis until institutionalization and death in people with dementia from routine nationally representative databases are lacking. Methods We selected 9230 people with dementia and 24,624 matched controls from family physicians’ electronic records linked with national administrative databases to analyze time until institutionalization and death and associated factors. Results Median time from recorded diagnosis until institutionalization and until death for people with dementia was 3.9 and 5.0 years, respectively, which was considerably shorter than for controls. Once institutionalized, median time to death was longer for persons with dementia (2.5 years) than for controls (1.2 years). Older age and receiving home care were the strongest predictors of shorter time until institutionalization and death in people with dementia. Gender, cohabitation, migration status, frailty, polypharmacy, and dementia medication were other significant factors. Discussion The estimates could help to inform patients, their families, and policymakers about probable trajectories

Effects of intermittent presentation of cultural consequences on interlocking behavioral contingencies and their aggregate products

The social behavior of an individual can be interlocked with the others and give rise to interlocking behavioral contingencies (IBCs), whose coordination can generate aggregate products (APs) with the function of cultural consequences (CCs). Such elements may take part in a metacontingency, thus configuring the selection process at the cultural level. In complex cultural practices, a receiving system (RS) can perform the function of releasing CCs. Experiments have shown that CCs can select and keep the IBCs and their APs. Other studies have suggested the possibility of maintain and even install the IBCs and their APs through intermittent CCs on VR2, and extinguish them. The present study investigated the possibility of maintain the IBCs and their APs by applying intermittent CCs on a CRF, FR2, VR3, FR3 and VR3 schedule and the effect of the subsequent suspension of CCs. The study included 93 participants from higher education, appointed to one of five experiments. Each group had one to three participants at the same moment, and each participant chose a line in a 10x10 matrix with numbered rows of five different colors and alphabetically named columns. After each participant chooses a row, the experimenter chose a column whose intersection cell could contain a black circle that gives a token worth 10 cents for the participant. The same procedure was then applied to the other participants. In some phases, when the color of the line chosen by each participant differed from the others it was applied a CC on the group, in the form of stickers exchangeable for donation school supplies. The groups that composed the experiment were exposed to different metacontingencies: CRF, FR2, VR2, VR3 and FR3, and all were exposed to a final extinction. All groups began with one participant on the selection phase and gradually the complexity was increased adding participants and changing metacontingencies. At the end of the study, participants answered a brief questionnaire. The results corroborated the data found in literature, suggesting the selection of IBCs and their PAs and their maintenance through the application of intermittent CCs in schedules of FR2, VR2, VR3 and FR3. The study was unable to determine whether there were differences in resistance to extinction of IBCs comparing the various tested schedules, because this was not clearly obtained. However, an analysis of cultural variability suggests the beginning of an extinction process due to increased variability of the IBCs along extinction. It also suggests IBCs should conform to analogous principles to those observed in operant variability. The verbal descriptions of the contingencies of reinforcement were very common among participants, but the descriptions of metacontingencies occurred with lower frequency, especially those exposed to Extinction and VR3.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoO comportamento social de um indivíduo pode se entrelaçar com o de outros e dar origem a contingências comportamentais entrelaçadas (CCEs), cuja coordenação pode gerar produtos agregados (PAs) com função de consequências culturais (CCs). Tais elementos podem tomar parte uma metacontingência, configurando assim o processo seletivo no nível cultural. Em praticas culturais complexas, um sistema receptor (SR) pode exercer a função de liberador de CCs. Experimentos demonstraram que CCs podem selecionar e manter as CCEs e seus PAs. Outros estudos sugeriram a possibilidade de manter, e até instalar, as CCEs e seus PAs por meio de CCs intermitentes em VR2, bem como extingui-las. O presente trabalho buscou investigar a possibilidade de manutenção das CCEs e seus PAs por meio de aplicação de intermitente de CCs em um esquema de CRF, FR2, VR3, FR3 e VR3 assim como o efeito da suspensão posterior de CCs. Participaram do estudo 93 participantes de cursos superiores, designados a um de cinco experimentos. Cada grupo teve de um a três participantes num mesmo momento, e cada participante escolheu a cada ciclo uma linha numa matriz de 10x10 com linhas de cinco diferentes cores numeradas e colunas alfabeticamente nomeadas. Após cada participante escolher uma linha, o experimentador escolhia uma coluna, cuja célula de interseção podia conter um círculo que equivalia a uma ficha no valor de 10 centavos para o participante. O mesmo procedimento era então aplicado aos demais participantes. Em algumas fases, quando a cor da linha escolhida por cada participante diferisse dos demais aplicava-se uma consequência cultural sobre o grupo, na forma de adesivos trocáveis por materiais escolares para doação. Os grupos que compuseram os experimentos foram expostos a diferentes metacontingências: CRF, FR2, VR2, FR3 e VR3 e todos foram expostos a uma fase final de Extinção. Todos os grupos começavam com um participante numa fase de seleção operante e gradualmente a complexidade foi sendo ampliada com aumento de participantes e mudança de metacontingências. Ao final da pesquisa, os participantes responderam um breve questionário. Os resultados corroboraram os dados encontrados na literatura, sugerindo a seleção de CCEs e seus PAs e sua manutenção por meio da aplicação de CCs em esquemas intermitentes de FR2, VR2, FR3 e VR3. Não foi possível verificar se existiam diferenças na resistência à extinção das CCEs entre os diferentes esquemas testados, pois esta não foi claramente obtida. Entretanto, uma análise da variabilidade cultural sugere o início de um processo de extinção devido ao aumento da variabilidade das CCEs na fase de extinção. Aponta também que as CCEs podem obedecer a princípios análogos aos observados na variabilidade operante. As descrições verbais das contingências de reforço foram muito frequentes entre os participantes, porém as descrições das metacontingências aconteceram com frequência mais baixa, especialmente nos participantes exposto à Extinção e VR3

Microarray analysis reveals pivotal divergent mRNA expression profiles early in the development of either compensated ventricular hypertrophy or heart failure

Myocardial right ventricular (RV) hypertrophy due to pulmonary hypertension is aimed at normalizing ventricular wall stress. Depending on the degree of pressure overload, RV hypertrophy may progress to a state of impaired contractile function and heart failure, but this cannot be discerned during the early stages of ventricular remodeling. We tested whether critical differences in gene expression profiles exist between ventricles before the ultimate development of either a compensated or decompensated hypertrophie phenotype. Both phenotypes were selectively induced in Wistar rats by a single subcutaneous injection of either a low or a high dose of the pyrrolizidine alkaloid monocrotaline (MCT). Spotted oligonucleotide microarrays were used to investigate pressure-dependent cardiac gene expression profiles at 2 wk after the MCT injections, between control rats and rats that would ultimately develop either compensated or decompensated hypertrophy. Clustering of significantly regulated genes revealed specific expression profiles for each group, although the degree of hypertrophy was still similar in both. The ventricles destined to progress to failure showed activation of pro-apoptotic pathways, particularly related to mitochondria, whereas the group developing compensated hypertrophy showed blocked pro-death effector signaling via p38-MAPK, through upregulation of MAPK phosphatase-1. In summary, we show that, already at an early time point, pivotal differences in gene expression exist between ventricles that will ultimately develop either a compensated or a decompensated phenotype, depending on the degree of pressure overload. These data reveal genes that may provide markers for the early prediction of clinical outcome as well as potential targets for early intervention