153 research outputs found
Building intersubjectivity in blended problem-solving tasks
This paper aims to shed light on the process of building intersubjectivity between student-student dyads in a blended educational context. Three girls and five boys, 17 to 18 years old, participated in two types of problem-solving tasks. They formed four dyads and were required to negotiate aloud what to post in a web-forum. Dyads were video recorded, with eight sessions in total. The same pairs participated in both tasks. We are interested in understanding how the intersubjective processes were affected by the tasks and by the dyads. The two tasks differ concerning the structure of the problems. The first task was based on two short papers – one pro and other con – referring to a problem close to students' real life: the use of digital devices in class. The second problem was based on perspective-taking: dyads were required to imagine “How would the school of the future look in 20 years.” Data were analysed through a purpose-built codebook, comprising five macro-categories and 21 subcategories. Altogether, our results indicate an effect of both the type of task and of dyads' specific style of interaction. Nevertheless, a five-step process featuring intersubjectivity was found. Practical implications for teachers and educators are highlighted
Blending academic and professional learning in a university course for future e-learning specialists: The perspective of company tutors
Blended learning usually refers to the combination of online/offline instructional methods. In this paper, we describe a university course in “E-learning Psychology” designed to blend not only modes of teaching, tools, and media, but also learning contexts; specifically, academic and professional contexts. To achieve an effective blend of learning contexts, students were monitored by academic and company tutors through an instant messaging app (WhatsApp). The unique contribution of the company tutor to the blending of academic and professional contexts is explored. By qualitatively analyzing (i) process data (four WhatsApp log chats) and (ii) self-report data (interviews with six company tutors), we found that the company tutor contributed to both the traditional blended dimension (mixing online and offline) and to the blend of the academic and professional contexts. When company tutors participated in the chat, students moved from an organizational dynamic, featuring chats monitored by only the academic tutor, toward a more collaborative and reflective dynamic. The company tutors considered the opportunity to blend academic and professional contexts as the best aspect of the course for both themselves as educators/company representatives, and for the students. This paper offers insights into the ongoing discussion about what blended is—or should be—and the role of company tutors in blending educational contexts
Understanding I/We positions in a blended university course: Polyphony and chronotopes as dialogical features.
This paper uses Dialogical Self Theory to explore university students’ I/We positions before and after participating in a blended course with both individual and collaborative learning activities. Two focus group discussions were held; one at the beginning and the other one at the end (18 students in total; 3 M, 15F; average age 24 years old). The focus groups were analyzed through discursive analysis by referring to the Bakhtinian concepts of chronotope and polyphony, as dialogical features of positioning. Results show that at the end of the course the polyphony became richer, including also technology. This was initially “suppressed” and became later a voice supporting both We-position and collaborative learning. A shift from initial I-positions rooted in a broad chronotope (including past, present and future) toward We-positions placed in the specific and situated chronotope of the course occurred. This result poses the question of sustainability and transferability of innovation
Four-dimensional imaging and quantification of viscous flow sintering within a 3D printed bioactive glass scaffold using synchrotron X-ray tomography
Bioglass® was the first material to form a stable chemical bond with human tissue. Since its discovery, a key goal was to produce three-dimensional (3D) porous scaffolds which can host and guide tissue repair, in particular, regeneration of long bone defects resulting from trauma or disease. Producing 3D scaffolds from bioactive glasses is challenging because of crystallization events that occur while the glass particles densify at high temperatures. Bioactive glasses such as the 13–93 composition can be sintered by viscous flow sintering at temperatures above the glass transition onset (T_{g}) and below the crystallization temperature (T_{c}). There is, however, very little literature on viscous flow sintering of bioactive glasses, and none of which focuses on the viscous flow sintering of glass scaffolds in four dimensions (4D) (3D + time). Here, high-resolution synchrotron-sourced X-ray computed tomography (sCT) was used to capture and quantify viscous flow sintering of an additively manufactured bioactive glass scaffold in 4D. In situ sCT allowed the simultaneous quantification of individual particle (local) structural changes and the scaffold's (global) dimensional changes during the sintering cycle. Densification, calculated as change in surface area, occurred in three distinct stages, confirming classical sintering theory. Importantly, our observations show for the first time that the local and global contributions to densification are significantly different at each of these stages: local sintering dominates stages 1 and 2, while global sintering is more prevalent in stage 3. During stage 1, small particles coalesced to larger particles because of their higher driving force for viscous flow at lower temperatures, while large angular particles became less faceted (angular regions had a local small radius of curvature). A transition in the rate of sintering was then observed in which significant viscous flow occurred, resulting in large reduction of surface area, total strut volume, and interparticle porosity because the majority of the printed particles coalesced to become continuous struts (stage 2). Transition from stage 2 to stage 3 was distinctly obvious when interparticle pores became isolated and closed, while the sintering rate significantly reduced. During stage 3, at the local scale, isolated pores either became more spherical or reduced in size and disappeared depending on their initial morphology. During stage 3, sintering of the scaffolds continued at the strut level, with interstrut porosity reducing, while globally the strut diameter increased in size, suggesting overall shrinkage of the scaffold with the flow of material via the strut contacts. This study provides novel insights into viscous flow in a complex non-idealized construct, where, locally, particles are not spherical and are of a range of sizes, leading to a random distribution of interparticle porosity, while globally, predesigned porosity between the struts exists to allow the construct to support tissue growth. This is the first time that the three stages of densification have been captured at the local and global scales simultaneously. The insights provided here should accelerate the development of 3D bioactive glass scaffolds
A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating and painful cancers. Pancreatic cancer is often highly resistant to therapy owing to inherent chemoresistance and the desmoplastic response that creates a barrier of fibrous tissue preventing transport of chemotherapeutics into the tumor. The growth of the tumor in pancreatic cancer often leads to invasion of other organs and partial or complete biliary obstruction, inducing intense pain for patients and necessitating tumor resection or repeated stenting. Here, we have developed a delivery device to provide enhanced palliative therapy for pancreatic cancer patients by providing high concentrations of chemotherapeutic compounds locally at the tumor site. This treatment could reduce the need for repeated procedures in advanced PDAC patients to debulk the tumor mass or stent the obstructed bile duct. To facilitate clinical translation, we created the device out of currently approved materials and drugs. We engineered an implantable poly(lactic-co-glycolic)-based biodegradable device that is able to linearly release high doses of chemotherapeutic drugs for up to 60 days. We created five patient-derived PDAC cell lines and tested their sensitivity to approved chemotherapeutic compounds. These in vitro experiments showed that paclitaxel was the most effective single agent across all cell lines. We compared the efficacy of systemic and local paclitaxel therapy on the patient-derived cell lines in an orthotopic xenograft model in mice (PDX). In this model, we found up to a 12-fold increase in suppression of tumor growth by local therapy in comparison to systemic administration and reduce retention into off-target organs. Herein, we highlight the efficacy of a local therapeutic approach to overcome PDAC chemoresistance and reduce the need for repeated interventions and biliary obstruction by preventing local tumor growth. Our results underscore the urgent need for an implantable drug-eluting platform to deliver cytotoxic agents directly within the tumor mass as a novel therapeutic strategy for patients with pancreatic cancer
Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: a retrospective, multicenter, real-world study
Background: Despite its proven activity as third-line treatment in gastrointestinal stromal tumors (GIST), regorafenib can present a poor tolerability profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract regorafenib-related adverse events and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of regorafenib in patients with metastatic GIST, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off). Patients and methods: Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify patients with GIST who had received regorafenib from February 2013 to January 2021. The Kaplan–Meier method was used to estimate survival and the log-rank test to make comparisons. Results: Of a total of 152 patients with GIST, 49 were treated with standard dose, while 103 received personalized schedules. At a median follow-up of 36.5 months, median progression-free survival was 5.6 months [95% confidence interval (CI) 3.73-11.0 months] versus 9.7 months (95% CI 7.9-14.5 months) in the standard-dose and the personalized schedule groups, respectively [hazard ratio (HR) 0.51; 95% CI 0.34-0.75; P = 0.00052]. Median overall survival was 16.6 months (95% CI 14.1-21.8 months) versus 20.5 months (95% CI 15.0-25.4 months), respectively (HR 0.75; 95% CI 0.49-1.22; P = 0.16). Conclusions: Regorafenib-personalized schedules are commonly adopted in daily clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Therefore, regorafenib treatment optimization in patients with GIST may represent the best strategy to maximize long-term therapy
A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating and painful cancers. It is often highly resistant to therapy owing to inherent chemoresistance and the desmoplastic response that creates a barrier of fibrous tissue preventing transport of chemotherapeutics into the tumor. The growth of the tumor in pancreatic cancer often leads to invasion of other organs and partial or complete biliary obstruction, inducing intense pain for patients and necessitating tumor resection or repeated stenting. Here, we have developed a delivery device to provide enhanced palliative therapy for pancreatic cancer patients by providing high concentrations of chemotherapeutic compounds locally at the tumor site. This treatment could reduce the need for repeated procedures in advanced PDAC patients to debulk the tumor mass or stent the obstructed bile duct. To facilitate clinical translation, we created the device out of currently approved materials and drugs. We engineered an implantable poly(lactic-co-glycolic)-based biodegradable device that is able to linearly release high doses of chemotherapeutic drugs for up to 60 days. We created five patient-derived PDAC cell lines and tested their sensitivity to approved chemotherapeutic compounds. These in vitro experiments showed that paclitaxel was the most effective single agent across all cell lines. We compared the efficacy of systemic and local paclitaxel therapy on the patient-derived cell lines in an orthotopic xenograft model in mice (PDX). In this model, we found up to a 12-fold increase in suppression of tumor growth by local therapy in comparison to systemic administration and reduce retention into off-target organs. Herein, we highlight the efficacy of a local therapeutic approach to overcome PDAC chemoresistance and reduce the need for repeated interventions and biliary obstruction by preventing local tumor growth. Our results underscore the urgent need for an implantable drug-eluting platform to deliver cytotoxic agents directly within the tumor mass as a novel therapeutic strategy for patients with pancreatic cancer. Keywords: Pancreatic cancer; Chemoresistance; Local delivery; Patient-derived xenograft; Paclitaxel; Poly(lactic-co-glycolic acid)National Institutes of Health (U.S.) (Grant P30-CA14051
Recommended from our members
Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway
Cancer cells exhibit metabolic dependencies that distinguish them from their normal counterparts1. Among these addictions is an increased utilization of the amino acid glutamine (Gln) to fuel anabolic processes2. Indeed, the spectrum of Gln-dependent tumors and the mechanisms whereby Gln supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of Gln utilization in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumor growth. While most cells utilize glutamate dehydrogenase (GLUD1) to convert Gln-derived glutamate (Glu) into α-ketoglutarate in the mitochondria to fuel the tricarboxylic acid (TCA) cycle, PDAC relies on a distinct pathway to fuel the TCA cycle such that Gln-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate (OAA) by aspartate transaminase (GOT1). Subsequently, this OAA is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP+ ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as Gln deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of Gln metabolism is mediated by oncogenic Kras, the signature genetic alteration in PDAC, via the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumors
- …