A convergence on Boolean algebras generalizing the convergence on the Aleksandrov cube

We compare the forcing related properties of a complete Boolean algebra B with the properties of the convergences $\lambda_s$ (the algebraic convergence) and $\lambda_{ls}$ on B generalizing the convergence on the Cantor and Aleksandrov cube respectively. In particular we show that $\lambda_{ls}$ is a topological convergence iff forcing by B does not produce new reals and that $\lambda_{ls}$ is weakly topological if B satisfies condition $(\hbar)$ (implied by the ${\mathfrak t}$-cc). On the other hand, if $\lambda_{ls}$ is a weakly topological convergence, then B is a $2^{\mathfrak h}$-cc algebra or in some generic extension the distributivity number of the ground model is greater than or equal to the tower number of the extension. So, the statement "The convergence $\lambda_{ls}$ on the collapsing algebra B=\ro ((\omega_2)^{<\omega}) is weakly topological" is independent of ZFC

La relación entre Curso de articulación o propedéutico y rendimiento de los alumnos en la Cátedra de Introducción a la Teoría Contable de la Facultad de Ciencias Económicas de la Universidad Nacional de Entre Ríos

El Proyecto de Investigación denominado “La relación entre Curso de articulación o propedéutico y rendimiento de los alumnos en la Cátedra de Introducción a la Teoría Contable de la Facultad de Ciencias Económicas de la Universidad Nacional de Entre Ríos”, basado en las Cohortes 2010-2011, 2011-2012 y 2012-2013, tiene como objetivo realizar el seguimiento de los resultados en exámenes parciales y finales realizados por los alumnos de la Cátedra de Introducción a la Teoría Contable, luego de haber cursado y aprobado el Curso de Articulación o Propedéutico, respectivamente en forma obligatoria para poder acceder al cursado de la cátedra mencionada. La inquietud de relacionar el curso de articulación o propedéutico con el rendimiento en la cátedra, se origina en tratar de establecer si existen diferencias en los resultados de las evaluaciones, según se haya participado o no de los cursos mencionados, considerando una instancia propicia para realizar el estudio el inicio del ciclo lectivo 2011, en que se establece la obligatoriedad de esas instancias.El proyecto de articulación está destinado a los alumnos aspirantes a ingresar a la Facultad de Ciencias Económicas, con el propósito de desarrollar contenidos teóricos y prácticos acordes con los criterios adoptado por la cátedra de “Introducción a la Teoría Contable”. Con él se pretende lograr dos objetivos: por un lado, nivelar el conocimiento de los alumnos formados en la materia contable y, por otro lado, servir de curso introductorio para aquellos alumnos no formados en dicha materia.El presente informe expone el análisis descriptivo de los datos de los ingresantes 2010, 2011, 2012 y 2013 como así también estudia posibles relaciones entre la obligatoriedad implementada en el curso de articulación o propedéutico a partir del año 2011 y el rendimiento observado en la asignatura Introducción a la Teoría Contabl

Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma

BACKGROUND & AIMS: We investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line. METHODS: In this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events. RESULTS: Of 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively. CONCLUSIONS: ICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials. IMPACT AND IMPLICATIONS: Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma

Background and Aims Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC. Methods 191 consecutive patients from eight centres receiving atezolizumab and bevacizumab were included. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in older (age ≥ 65 years) and younger (age < 65 years) age patients. Treatment-related adverse events (trAEs) were evaluated. Results The elderly (n = 116) had higher rates of non-alcoholic fatty liver disease (19.8% vs. 2.7%; p < .001), presenting with smaller tumours (6.2 cm vs 7.9 cm, p = .02) with less portal vein thrombosis (31.9 vs. 54.7%, p = .002), with fewer patients presenting with BCLC-C stage disease (50.9 vs. 74.3%, p = .002). There was no significant difference in OS (median 14.9 vs. 15.1 months; HR 1.15, 95% CI 0.65–2.02 p = .63) and PFS (median 7.1 vs. 5.5 months; HR 1.11, 95% CI 0.54–1.92; p = .72) between older age and younger age. Older patients had similar ORR (27.6% vs. 20.0%; p = .27) and DCR (77.5% vs. 66.1%; p = .11) compared to younger patients. Atezolizumab-related (40.5% vs. 48.0%; p = .31) and bevacizumab-related (44.8% vs. 41.3%; p = .63) trAEs were comparable between groups. Rates of grade ≥3 trAEs and toxicity-related treatment discontinuation were similar between older and younger age patients. Patients 75 years and older had similar survival and safety outcomes compared to younger patients. Conclusions Atezolizumab and bevacizumab therapy is associated with comparable efficacy and tolerability in older age patients with unresectable HCC

A Role for Glutamate Transporters in the Regulation of Insulin Secretion

In the brain, glutamate is an extracellular transmitter that mediates cell-to-cell communication. Prior to synaptic release it is pumped into vesicles by vesicular glutamate transporters (VGLUTs). To inactivate glutamate receptor responses after release, glutamate is taken up into glial cells or neurons by excitatory amino acid transporters (EAATs). In the pancreatic islets of Langerhans, glutamate is proposed to act as an intracellular messenger, regulating insulin secretion from beta-cells, but the mechanisms involved are unknown. By immunogold cytochemistry we show that insulin containing secretory granules express VGLUT3. Despite the fact that they have a VGLUT, the levels of glutamate in these granules are low, indicating the presence of a protein that can transport glutamate out of the granules. Surprisingly, in beta-cells the glutamate transporter EAAT2 is located, not in the plasma membrane as it is in brain cells, but exclusively in insulin-containing secretory granules, together with VGLUT3. In EAAT2 knock out mice, the content of glutamate in secretory granules is higher than in wild type mice. These data imply a glutamate cycle in which glutamate is carried into the granules by VGLUT3 and carried out by EAAT2. Perturbing this cycle by knocking down EAAT2 expression with a small interfering RNA, or by over-expressing EAAT2 or a VGLUT in insulin granules, significantly reduced the rate of granule exocytosis. Simulations of granule energetics suggest that VGLUT3 and EAAT2 may regulate the pH and membrane potential of the granules and thereby regulate insulin secretion. These data suggest that insulin secretion from beta-cells is modulated by the flux of glutamate through the secretory granules