On the ergodic theory of impulsive semiflows

We consider impulsive semiflows and establish sufficient conditions to the existence of invariant measures. Namely, the impulsive set and its image are both submanifolds of codimension one that are transversal to the flow direction. Moreover, we show that under the same conditions a Variational Principle holds

Chapeuzinho Amarelo: um novo sentido para uma velha história

Little Yellow Riding Hood is one of the rewritings of Little Red Riding Hood in which the difference breaks out in the discourse, producing new meanings - polysemy. The traditional subject-positions of the Wolf and Little Riding Hood are totally reversed due to the change in meaning of fear. These subjectpositions are analysed as well as the images that accompany them and that are maintained in the interdiscourse by paraphrastic rewritings. The Wolf, occupying the position of the dominator, with his characteristics of evil and aggressiveness; Little Riding Hood, occupying the position of the dominated, with her characteristics of ingenuousness and impotence, being fear the determiner of these positions. With the parody by Chico Buarque, these images are deconstructed and the meanings are dislocated through linguistic hints that become evident on the linguistic base; these bring forth the new image of Little Yellow Riding Hood, now strong and domineering and of the Wolf, now weak and dominated.Chapeuzinho Amarelo é uma das reescrituras de Chapeuzinho Vermelho em que o diferente irrompe no discurso, produzindo sentidos novos - a polissemia. As tradicionais posições-sujeito do Lobo e de Chapeuzinho sofrem uma reversão total em função da mudança de sentido do medo. São analisadas as posições-sujeito bem como as imagens que as acompanham e que se mantêm no interdiscurso através das reescrituras parafrásticas. O Lobo, ocupando a posição de dominador, com suas características de maldade e agressividade; Chapeuzinho, ocupando a posição de dominada, com suas características de ingenuidade e impotência, sendo o lugar do medo determinante dessas posições. A partir da paródia de Chico Buarque, mostrase a desconstrução dessas imagens, o deslocamento dos sentidos através das pistas que se evidenciam na base lingüística e que fazem surgir a imagem de Chapeuzinho Amarelo, forte e dominadora e do Lobo, fraco e dominado

La differenciation plastidale chez l'acetabulaire etudiee par l'emission de fluorescence a 77° K

Plastidal differentiation in Acetabularia studied by fluorescence emission at 77° K. Examination of the 77° K fluorescence emission spectra provides a good criterion for distinguishing chloroplasts of the apical from those of the basal region of the stalk of Acetabularia cells at stage 4. Extraction increases the differences between the emission spectra of apical and basal chloroplasts. By using the 77° K fluorescence emission spectra technique, it is possible to show the differentiation of the plastids and to follow it during the regeneration of anucleate and nucleate fragments. © 1975

Projeto pró-língua : um novo olhar sobre o ensinar e o aprender à luz de novas teorias

04

Drug holidays and overall survival of patients with metastatic colorectal cancer

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni-and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni-and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22\u20132.32; p = 0.002 and HR,4.89; 95% CI, 3.33\u20137.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer

Plasma-Based Longitudinal Evaluation of ESR1 Epigenetic Status in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer

Background: Endocrine therapy (ET) is the mainstay of treatment for hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer; however, adaptive mechanisms emerge in about 25\u201330% of cases through alterations in the estrogen receptor ligand-binding domain, with a consequent ligand-independent estrogen receptor activity. Epigenetic-mediated events are less known and potentially involved in alternative mechanisms of resistance. The aim of this study was to test the feasibility of estrogen receptor 1 (ESR1) epigenetic characterization through liquid biopsy and to show its potential longitudinal application for an early ET sensitivity assessment. Methods: A cohort of 49 women with hormone receptor-positive HER2-negative MBC was prospectively enrolled and characterized through circulating tumor DNA using methylation-specific droplet digital PCR (MS-ddPCR) before treatment start (BL) and after 3 months concomitantly with computed tomography (CT) scan restaging (EV1). ESR1 epigenetic status was defined by assessing the methylation of its main promoters (promA and promB). The most established cell-free tumor DNA (ctDNA) factors associated with ET resistance [ESR1 and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations] were assessed through next-generation sequencing. Associations were tested through Mann\u2013Whitney U test, matched pairs variations through Wilcoxon signed rank test, and survival was analyzed by log-rank test. Results: The ET backbone was mainly based on aromatase inhibitors (AIs) (70.83%) in association with CDK4/6 inhibitors (93.75%). Significantly lower promA levels at baseline were observed in patients with liver metastases (P = 0.0212) and in patients with ESR1 mutations (P = 0.0091). No significant impact on PFS was observed for promA (P = 0.3777) and promB (P = 0.7455) dichotomized at the median while a 652-fold increase in promB or in either promA or promB at EV1 resulted in a significantly worse prognosis (respectively P = 0.0189, P = 0.0294). A significant increase at EV1 was observed for promB among patients with PIK3CA mutation (P = 0.0173). A trend was observed for promB in ESR1 wild-type patients and for promA in the ESR1 mutant subgroup. Conclusion: The study proofed the concept of an epigenetic characterization strategy based on ctDNA and is capable of being integrated in the current clinical workflow to give useful insights on treatment sensitivity

First- and second-line treatment strategies for hormone-receptor (HR)-positive HER2-negative metastatic breast cancer: A real-world study

Background: Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L. Materials and methods: 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated. Results: At 1stL, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2ndL, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1stL ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2ndL ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1stL ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1stL ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1stL ET-CDK4/6i followed by CT had worse OS compared to 1stL ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2ndL influenced 2ndL treatment choice (ET vs. CT) after ET-CDKi. Conclusion: Our real-world data demonstrated that ET-CDKi represents the best option for 1stL luminal-MBC compared to ET and CT. Also, the present study pointed out that 2ndL ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines