Ex-vivo recruitment and x-ray assessment of donor lungs in a challenging retrieval from a donor supported by lvad using the portable normothermic perfusion system: A case report

Lung transplantation (LTx) is limited by the shortage of suitable donors. To overcome this problem, many programs have begun to use donors with extended criteria (marginal donors). However, brain-dead patients with implanted mechanical circulatory support system have rarely been considered as potential lung donors. This case demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system despite the possible difficulties of lung retrieval. CASE PRESENTATION: Our case presents a successful procurement and bilateral lung transplantation from a donor supported by a left ventricular assist device (LVAD) who experienced an intraoperatively haemodynamic complication. The use of portable normothermic perfusion device let us to reduce ischemic injury and assess these marginal donor lungs helping us to determine the clinical suitability for transplantation. Given our extensive experience with the device instrumentation and management, the EVLP process was uneventful with excellent post-transplant course. CONCLUSIONS: This case report demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system using the portable normothermic perfusion platform to assess and preserve these donor lungs

A constitutive active MAPK/ERK pathway due to BRAFV600E positively regulates AHR pathway in PTC

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor mediating the toxicity and tumor-promoting properties of dioxin. AHR has been reported to be overexpressed and constitutively active in a variety of solid tumors, but few data are currently available concerning its role in thyroid cancer. In this study we quantitatively explored a series of 51 paired-normal and papillary thyroid carcinoma (PTC) tissues for AHR-related genes. We identified an increased AHR expression/activity in PTC, independently from its nuclear dimerization partner and repressor but strictly related to a constitutive active MAPK/ERK pathway. The AHR up-regulation followed by an increased expression of AHR target genes was confirmed by a meta-analysis of published microarray data, suggesting a ligand-independent active AHR pathway in PTC. In-vitro studies using a PTC-derived cell line (BCPAP) and HEK293 cells showed that BRAF(V600E) may directly modulate AHR localization, induce AHR expression and activity in an exogenous ligand-independent manner. The AHR pathway might represent a potential novel therapeutic target for PTC in the clinical practice

Depuration Capacity of Mussels (Mytilus galloprovincialis) in Presence of Marteilia Spp. Parasites

Bivalve molluscs are filter-feeding organisms present in the water column: during their activity, they could retain micro-organisms that are potentially dangerous to human health. For this reason, EU Regulations may require that a purification treatment be performed prior to bivalve trade. The length of the purification process could be affected by stress factors, such as parasitic infections. The purpose of this study was to determine if the presence of Marteilia spp. parasite in shellfish could modify time and efficacy of their microbiological purification treatment, in order to set up specific protocols. Lysosomal membrane stability, phagocytosis capacity, granulocyte/hyalinocyte rate and neutral lipid accumulation are biomarkers used to evaluate shellfish physiological state. These biomarkers were used to exclude any differences caused by stressor factors that could affect the purification results. Mussels were sampled from two different production areas. The presence or absence of parasites was confirmed by cytological test. Both groups of parasitized and non-parasitized mussels were contaminated with E.coli: they were then sampled for microbiological analyses and tested for biomarkers for up to 70 hours of purification. Parasitized and non-parasitized molluscs did not show any differences in levels of E. coli after 12, 24, 36, 48 and 70 hours of depuration. In relation to biomarkers, mussels seem to react to Lysosomal membrane stability in presence of Marteilia. The present study shows that the presence of Marteilia spp. does not affect the purification rate of mussels

Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma

BACKGROUND: Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results. METHODS: Phase II, open-label study of the combination of chemotherapy (pemetrexed 500 mg/m(2)+cisplatin 75 mg/m(2) IV every 21 days × 3 cycles), followed by surgery (en-bloc extrapleural pneumonectomy, 3–8 weeks after chemotherapy) and hemithoracic radiation (total radiation beam 54 Gy, received 4–8 weeks post-surgery). The primary endpoint was event-free survival, defined as the time from enrollment to time of first observation of disease progression, death due to any cause, or early treatment discontinuation. RESULTS: Fifty-four treatment-naïve patients with T1-3 N0-2 malignant pleural mesothelioma were enrolled, 52 (96.3%) completed chemotherapy, 45 (83.3%) underwent surgery, 22 (40.7%) completed the whole treatment including 90-day post-radiation follow-up. The median event-free survival was 6.9 months (95%CI: 5.0-10.5), median overall survival was 15.5 months (95%CI 11.0-NA) while median time-to-tumor response was 4.8 months (95%CI: 2.5-8.0). Eighteen (33.3%) and 13 (24.1%) patients were still event-free after 1 and 2 years, respectively. The most common treatment-emergent adverse events were nausea (63.0%), anemia (51.9%) and hypertension (42.6%). Following two cardiopulmonary radiation-related deaths the protocol was amended (21 [38.9%] patients were already enrolled in the study): the total radiation beam was reduced from 54 Gy to 50.4 Gy and a more accurate selection of patients was recommended. CONCLUSIONS: The combination of pemetrexed plus cisplatin followed by surgery and hemithoracic radiation is feasible and has a manageable toxicity profile in carefully selected patients. It may be worthy of further investigation. TRIAL REGISTRATION: Clinicaltrial.com registrationID #NCT00087698

"iCub, We Forgive You!" Investigating Trust in a Game Scenario with Kids

This study presents novel strategies to investigate the mutual influence of trust and group dynamics in children-robot interaction. We implemented a game-like experimental activity with the humanoid robot iCub and designed a questionnaire to assess how the children perceived the interaction. We also aim to verify if the sensors, setups, and tasks are suitable for studying such aspects. The questionnaires' results demonstrate that youths perceive iCub as a friend and, typically, in a positive way. Other preliminary results suggest that, generally, children trusted iCub during the activity and, after its mistakes, they tried to reassure it with sentences such as: "Don't worry iCub, we forgive you". Furthermore, trust towards the robot in group cognitive activity appears to change according to gender: after two consecutive mistakes by the robot, girls tended to trust iCub more than boys. Finally, no significant difference has been evidenced between different age groups across points computed from the game and the self-reported scales. The tool we proposed is suitable for studying trust in human-robot interaction (HRI) across different ages and seems appropriate to understand the mechanism of trust in group interactions

Modeling Visual Features to Recognize Biological Motion: A Developmental Approach

In this work we deal with the problem of designing and developing computational vision models – comparable to the early stages of the human development – using coarse low-level information. More specifically, we consider a binary classification setting to characterize biological movements with respect to non-biological dynamic events. To this purpose, our model builds on top of the optical flow estimation, and abstract the representation to simulate the limited amount of visual information available at birth. We take inspiration from known biological motion regularities explained by the Two-Thirds Power Law, and design a motion representation that includes different low-level features, which can be interpreted as the computational counterpart of the elements involved in the law. Our reference application is human-machine interaction, thus the experimental analysis is conducted on a set of videos depicting two different subjects performing a repertoire of dynamic gestures typical of such a setting (e.g. lifting an object, pointing, ...). Two slightly different viewpoints are considered. The contribution of our work is twofold. First, we show that the effects of the Two-Thirds Power Law can be appreciates on a video analysis setting. Second, we prove that, although the coarse motion representation, our model allows us to reach biological motion classification performances (around 89%) which are reminiscent of the abilities of very young babies. Moreover, our model shows tolerance to view-point changes

Detecting Biological Motion for Human-Robot Interaction: A Link between Perception and Action

One of the fundamental skills supporting safe and comfortable interaction between humans is their capability to understand intuitively each other's actions and intentions. At the basis of this ability is a special-purpose visual processing that human brain has developed to comprehend human motion. Among the first "building blocks" enabling the bootstrapping of such visual processing is the ability to detect movements performed by biological agents in the scene, a skill mastered by human babies in the first days of their life. In this paper, we present a computational model based on the assumption that such visual ability must be based on local low-level visual motion features, which are independent of shape, such as the configuration of the body and perspective. Moreover, we implement it on the humanoid robot iCub, embedding it into a software architecture that leverages the regularities of biological motion also to control robot attention and oculomotor behaviors. In essence, we put forth a model in which the regularities of biological motion link perception and action enabling a robotic agent to follow a human-inspired sensory-motor behavior. We posit that this choice facilitates mutual understanding and goal prediction during collaboration, increasing the pleasantness and safety of the interactio

Human- or object-like? Cognitive anthropomorphism of humanoid robots

Across three experiments (N = 302), we explored whether people cognitively elaborate humanoid robots as human- or object-like. In doing so, we relied on the inversion paradigm, which is an experimental procedure extensively used by cognitive research to investigate the elaboration of social (vs. non-social) stimuli. Overall, mixed-model analyses revealed that full-bodies of humanoid robots were subjected to the inversion effect (body-inversion effect) and, thus, followed a configural processing similar to that activated for human beings. Such a pattern of finding emerged regardless of the similarity of the considered humanoid robots to human beings. That is, it occurred when considering bodies of humanoid robots with medium (Experiment 1), high and low (Experiment 2) levels of human likeness. Instead, Experiment 3 revealed that only faces of humanoid robots with high (vs. low) levels of human likeness were subjected to the inversion effects and, thus, cognitively anthropomorphized. Theoretical and practical implications of these findings for robotic and psychological research are discussed

Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications

Background The PI3K/AKT/mTORC1 axis is implicated in hormone receptor-positive HER2-negative metastatic breast cancer (HR+ HER2- mBC) resistance to anti-estrogen treatments. Based on results of the BOLERO-2 trial, the mTORC1 inhibitor everolimus in combination with the steroidal aromatase inhibitor (AI) exemestane has become a standard treatment for patients with HR+ HER2- mBC resistant to prior non-steroidal AI therapy. In the recent SOLAR-1 trial, the inhibitor of the PI3K alpha subunit (p110 alpha) alpelisib in combination with fulvestrant prolonged progression-free survival (PFS) when compared to fulvestrant alone in patients with PIK3CA-mutated HR+ HER2- mBC that progressed after/on previous AI treatment. Therefore, two different molecules targeting the PI3K/AKT/mTORC1 axis, namely everolimus and alpelisib, are available for patients progressing on/after previous AI treatment, but it is unclear how to optimize their use in the clinical practice. Main body of the abstract Here, we reviewed the available clinical evidence deriving from the BOLERO-2 and SOLAR-1 trials to compare efficacy and safety profiles of everolimus and alpelisib in advanced HR+ HER2- BC treatment. Adding either compound to standard endocrine therapy provided similar absolute and relative PFS advantage. In the SOLAR-1 trial, a 76% incidence of grade (G) 3 or 4 (G3/G4) adverse events was reported, while G3/G4 toxicities occurred in 42% of patients in the BOLERO-2 trial. While alpelisib was only effective in patients with PIK3CA-mutated neoplasms, retrospective analyses indicate that everolimus improves exemestane efficacy independently of PIK3CA mutational status. Conclusions Based on the available efficacy and safety data, the "new" alpelisib may be burdened by higher incidence of severe adverse events, higher costs, and anticancer efficacy that is limited to PIK3CA-mutated tumors when compared to the "old" everolimus. Therefore, the everolimus-exemestane combination remains an effective and reasonably well-tolerated therapeutic option for HR+ HER2- mBC patients progressing after/on previous AI treatment, independently of PIK3CA mutational status

Flexible Approaches Based on Multistate Models and Microsimulation to Perform Real-World Cost-Effectiveness Analyses: An Application to Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors

Objectives: This study aims to show the application of flexible statistical methods in real-world cost-effectiveness analyses applied in the cardiovascular field, focusing specifically on the use of proprotein convertase subtilisin-kexin type 9 inhibitors for hyperlipidemia. Methods: The proposed method allowed us to use an electronic health database to emulate a target trial for cost-effectiveness analysis using multistate modeling and microsimulation. We formally established the study design and provided precise definitions of the causal measures of interest while also outlining the assumptions necessary for accurately estimating these measures using the available data. Additionally, we thoroughly considered goodness-of-fit assessments and sensitivity analyses of the decision model, which are crucial to capture the complexity of individuals' healthcare pathway and to enhance the validity of this type of health economic models. Results: In the disease model, the Markov assumption was found to be inadequate, and a "time-reset" timescale was implemented together with the use of a time-dependent variable to incorporate past hospitalization history. Furthermore, the microsimulation decision model demonstrated a satisfying goodness of fit, as evidenced by the consistent results obtained in the short-term horizon compared with a nonmodel-based approach. Notably, proprotein convertase subtilisin-kexin type 9 inhibitors revealed their favorable cost-effectiveness only in the long-term follow-up, with a minimum willingness to pay of 39 000 Euro/life years gained. Conclusions: The approach demonstrated its significant utility in several ways. Unlike nonmodel-based or alternative model-based methods, it enabled to (1) investigate long-term cost-effectiveness comprehensively, (2) use an appropriate disease model that aligns with the specific problem under study, and (3) conduct subgroup-specific cost-effectiveness analyses to gain more targeted insights