On the SO(2,1) symmetry in General Relativity

The role of the SO(2,1) symmetry in General Relativity is analyzed. Cosmological solutions of Einstein field equations invariant with respect to a space-like Lie algebra G_r, with r between 3 and 6 and containing so(2,1) as a subalgebra, are also classified.Comment: 10 pages, latex, no figure

O papel do leitor em Felpo Filva, de Eva Furnari

In order to analyze the relationship between writer-reader and mediation of the text, it is necessary to identify the positions they occupy. Before the Internet, it was not common for the reader to approach the writer directly, except though letters. This virtual (but not digital) contact is modelling to understand the reader’s relationship with the author because, in the written lines, he ends up indicating how he understands himself and the other – in a game of faces, understood in this work as Kerbrat-Orecchioni (2006) it characterizes in conversation. In this hyper-gender, without socio-historical restrictions or of categorization (MAINGUENEAU, 2010), there is a mandatory provision that constrains the sender to identify his position from the moment he chooses how to address the recipient. In these forms of treatment, the relationships of preservation or threat to the in the light of what is extended or made explicit in the treatment given to the theme of the letter to be outlined. This article aims to identify the concepts of the reader in the correspondence exchanged by the main characters, Charlô and Felpo, core of the development of the narrative (FURNARI, 2006). These concepts allow us to comprehend, in a discursive and dialogical perspective, which boundaries remain for the reader towards the text and which are outdated.Para se analisar a relação entre escritor-leitor além da mediação do texto, é preciso identificar as posições que ocupam. Antes da internet, não era comum o leitor se aproximar diretamente do escritor, salvo por cartas. Esse contato virtual (mas não digital) é modelar para compreendermos a relação do leitor com o autor pois, nas linhas escritas, aquele acaba por indicar como compreende a si e ao outro – em um jogo das faces, entendida nesse trabalho como Kerbrat-Orecchioni (2006) a caracteriza na conversação. Nesse hipergênero, sem restrições sócio-históricas e de categorização (MAINGUENEAU, 2010), há uma disposição obrigatória que constrange o remetente a identificar sua posição a partir do momento em que escolhe como se dirigir ao destinatário. Nessas formas de tratamento, começam a ser delineadas as relações de preservação ou de ameaça à face que se estendem ou se explicitam no tratamento dado ao tema da carta. Nesse artigo, tem-se como objetivo identificar, nas cartas trocadas pelos personagens centrais para o desenvolvimento da narrativa do livro Felpo Filva (FURNARI, 2006), Charlô e Felpo, respectivamente leitora e escritor, as concepções desses papeis nos nossos dias na perspectiva discursivo-dialógica em que os limites do texto para o leitor são ultrapassados

Chimeric Antigen Receptor T-cell Therapy in Hematologic Malignancies and Patient-reported Outcomes: A Scoping Review

The inclusion of patient-reported outcome (PRO) measures in chimeric antigen receptor (CAR) T-cell therapy research is critical for understanding the impact of this novel approach from a unique patient standpoint. We performed a scoping review to map the available literature on the use of PRO measures in CAR T-cell therapy studies of patients with hematologic malignancies published between January 2015 and July 2022. Fourteen studies were identified, of which 7 (50%) were investigational early-phase trials, 6 (42.9%) were observational studies, and 1 (7.1%) was a pilot study. The EQ-5D and the PROMIS-29 were the 2 most frequently used PRO measures, being included in 6 (42.9%) and 5 (35.7%) studies, respectively. Despite differences in study designs, there seems to be evidence of improvements over time since CAR T-cell infusion in important domains such as physical functioning and fatigue, at least in patients who respond to therapy. Overall, the studies identified in our review have shown the added value of PRO assessment in CAR T-cell therapy research by providing novel information that complements the knowledge on safety and efficacy. However, there are several questions which remain to be answered in future research. For example, limited evidence exists regarding patient experience during important phases of the disease trajectory as only 4 (28.6%) and 5 (35.7%) studies provided information on PROs during the first 2 weeks from CAR T-cell infusion and after the first year, respectively. Time is ripe for a more systematic implementation of high-quality PRO assessment in future clinical trials and in real-life settings of patients treated with CAR T-cell therapy

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal–basal ganglia–thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmann's area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal–basal ganglia–thalamic network

Dietary calcium intake and adiposity in children and adolescents: Cross-sectional and longitudinal results from IDEFICS/I.Family cohort

Background and aims: Studies in children and adolescents suggest that higher dairy consumption may exert a protective effect on adiposity. However, only few studies examined the association between dietary calcium intake and body mass measures with conflicting results. We evaluated the association between total dietary calcium, calcium from dairy and non-dairy sources and anthropometric indices in a large European cohort of children and adolescents. Methods and Results: As many as 6, 696 children belonging to the IDEFICS study were eligible for the cross-sectional analysis (Boys = 51%; age 6.0 ± 1.8 years; mean ± SD). Of these, 2, 744 were re-examined six years later (Boys = 49.6%; age = 11.7 ± 1.8 years) in the framework of the I.Family study. The exposures were the baseline energy-adjusted total, dairy and non-dairy calcium intakes measured by a validated 24-h dietary recall. Multivariable linear regression was used to determine the association between calcium intake and z-scores of anthropometric indices (body mass index, BMI; waist circumference, WC; sum of skinfolds, SS; fat mass index, FMI) at baseline, and their variation over the 6 years follow-up. The association of dietary calcium with the incidence of overweight/obesity was also assessed. At baseline, an inverse association between total calcium intake and all the adiposity indices was consistently observed in boys, while only SS and FMI were significant in girls. The prevalence of overweight/obesity decreased significantly (P < 0.0001) across tertiles of calcium intake, in both sexes. Over the follow-up, boys with higher baseline calcium intake value showed significantly lower increase in BMI, WC and FMI z-scores, while in girls only a lower increase in WC z-score was observed. Only in boys, the risk to become overweight/obese decreased significantly across tertiles of calcium intake. Similar results were observed by analyzing only dietary calcium from dairy, while no association was observed between non-dairy calcium and adiposity indices. Conclusions: We showed in a large cohort of European children and adolescents that dietary calcium intake may play a role in the modulation of body fat in developmental age. The association between dietary calcium and adiposity indices was driven by dairy calcium, while no effect was observed for non-dairy calcium intake. The existence of a sex-related difference in the association deserves further investigations

Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies

Purpose Better tools are needed to estimate local recurrence (LR) risk after breast-conserving surgery (BCS) for DCIS. The DCIS score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS cohort (ODC) after BCS. We combined data from E5194 and ODC adjusting for clinicopathological factors to provide refined estimates of the 10-year risk of LR after treatment by BCS alone. Methods Data from E5194 and ODC were combined. Patients with positive margins or multifocality were excluded. Identical Cox regression models were fit for each study. Patient-specific meta-analysis was used to calculate precision-weighted estimates of 10-year LR risk by DS, age, tumor size and year of diagnosis. Results The combined cohort includes 773 patients. The DS and age at diagnosis, tumor size and year of diagnosis provided independent prognostic information on the 10-year LR risk (p ≤ 0.009). Hazard ratios from E5194 and ODC cohorts were similar for the DS (2.48, 1.95 per 50 units), tumor size ≤ 1 versus > 1–2.5 cm (1.45, 1.47), age ≥ 50 versus 15%) 10-year LR risk after BCS alone compared to utilization of DS alone or clinicopathological factors alone. Conclusions The combined analysis provides refined estimates of 10-year LR risk after BCS for DCIS. Adding information on tumor size and age at diagnosis to the DS adjusting for year of diagnosis provides improved LR risk estimates to guide treatment decision making

Randomized comparison of power Doppler ultrasound-directed excisional biopsy with standard excisional biopsy for the characterization of lymphadenopathies in patients with suspected lymphoma.

PURPOSE: The sensitivity of lymph node excisional biopsy requires validation. Power Doppler ultrasound (US) helps predict the malignant status of lymphadenopathies. We used power Doppler US to select for biopsy the lymph node most suspected of malignancy. PATIENTS AND METHODS: One hundred fifty-two patients having lymphadenopathies with clinical suspicion of lymphoma were divided into two well-matched groups and randomly assigned to undergo either standard or power Doppler US-directed lymph node excisional biopsy. RESULTS: Histology showed a malignancy in 64% of patients in the standard group (lymphoma, 49 patients; carcinoma, two patients) and in 87% of patients in the US-assisted group (lymphoma, 62 patients; carcinoma, one patient). There were significantly fewer biopsy-related complications in the assisted group than in the standard group. During the follow-up of the patients with lymph nodes reported as being reactive, 14 of 29 patients in the standard group were rebiopsied and were found to have lymphoma (13 patients) or carcinoma at the subsequent lymph node histology, whereas none of the patients in the assisted group (nine patients) required a second biopsy. Thus, biopsy provided false-negative results for malignancy in 21% of patients affected by lymphoma in the standard group and ever in the assisted group (P <.01). CONCLUSION: Power Doppler US is an accurate tool for screening lymphadenopathies to be removed by excisional biopsy in patients with suspected lymphoma

Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study

Purpose To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. Patients and Methods A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. Results There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). Conclusion For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians

Potential clinical implications of CD4+CD26high T cells for nivolumab treated melanoma patients

Background Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients’ outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe of-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will beneft from anti-PD-1 treatment avoiding unwanted side efects. However, the strength of CD26 expression on CD4+ T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies. Methods The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multiparametric fow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4+CD26high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4+CD26high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients. Results Circulating CD4+CD26high T cells were signifcantly reduced in melanoma patients compared to healthy subjects (p=0.001). In addition, a signifcant association was observed between a low baseline percentage of CD4+CD26high T cells (<7.3%) and clinical outcomes, measured as overall survival (p=0.010) and progression-free survival (p=0.014). Moreover, patients with clinical beneft from nivolumab therapy had signifcantly higher frequencies of circulating CD4+CD26high T cells than patients with non-clinical beneft (p=0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4+CD26high T cells was correlated with Disease Control Rate (p=0.014) and best Overall Response Rate (p=0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4+CD26high T cells were signifcantly higher in comparison with the frequencies measured at W0 (p<0.0001), aligning the cell counts with the ranges seen in the blood of healthy subjects