Clinical benefit of adding oxaliplatin to standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a meta-analysis : Oxaliplatin in neoadjuvant treatment for rectal cancer

Abstract. Background: To evaluate the treatment tolerance and clinical outcomes in patients aged 70 years and older with locally advanced oropharyngeal cancer treated by definitive intensity-modulated radiation therapy (IMRT). Patients and Methods: We retrospectively analyzed 15 consecutive elderly patients, with histologically-proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without involved lymph nodes at diagnosis, who received definitive sequential IMRT (70 Gy; 2 Gy/fraction). Adult Comorbidity Evaluation-27 (ACE-27) score was calculated and its influence on treatment tolerance and clinical outcomes was analyzed. Results: A total of 15 patients were included with a median age of 77 years (range=70-88 years). At baseline, 8 patients (53.3%) had an ACE-27 score of 1, and the remainder (n=7, 46.7%) had a comorbidity index of 0. All patients completed programmed IMRT treatment, without any reduction of total dose. Oral pain and mucositis were the most common acute side-effects, classified as grade 3 in 6 patients (40%) only. Xerostomia was reported in 13 patients (86.7%), without severe manifestation. There was no hematological toxicity. ACE-27 score was not related to higher severe acute toxicity. No patients experienced grade 3 or more late toxicity. Five-year overall survival and disease-free survival rates were 63.6% (95% confidence interval=32.7-83.3%) and 55% (95% confidence interval=24.4-77.6%), respectively. Comorbidity score did not influence survival outcomes, both overall survival (p=0.46) and disease-free survival (p=0.55). Conclusion: Treatment tolerance, as well as survival outcomes were good in elderly oropharyngeal cancer patients treated with definitive sequential IMRT. Due to age and comorbidity, no dose or volume reduction for IMRT should be considered in this setting of patients. A prospective randomized trial with a large sample size should be conducted to confirm our result

The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells

Inhibitors of kinesin spindle protein Eg5 are characterized by pronounced antitumor activity. Our group has recently synthesized and screened a library of 1,3,4-thiadiazoline analogues with the pharmacophoric structure of K858, an Eg5 inhibitor. We herein report the effects of K858 on four different breast cancer cell lines: MCF7 (luminal A), BT474 (luminal B), SKBR3 (HER2 like) and MDA-MB231 (basal like). We demonstrated that K858 displayed anti-proliferative activity on every analyzed breast cancer cell line by inducing apoptosis. However, at the same time, we showed that K858 up-regulated survivin, an anti-apoptotic molecule. We then performed a negative regulation of survivin expression, with the utilization of wortmannin, an AKT inhibitor, and obtained a significant increase of K858-dependent apoptosis. These data demonstrate that K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis

FACTORS INFLUENCING LOGISTICS SERVICE PROVIDERS' EFFICIENCY IN URBAN DISTRIBUTION SYSTEMS

The increased urbanization and the awareness of freight transportation impacts have stressed the importance of City Logistics (CL) as a comprehensive approach aimed at mitigating the negative effects of distribution activities without penalizing social, cultural, and economic issues. CL faces a relevant degree of complexity due to the characteristics of modern urban areas, such as traffic congestion, lack of parking spaces, high levels of pollution, and restrictions imposed by local regulations. This environment causes uncertainty about planning and managing delivery activities so that, if not properly organized, urban logistics might not meet its goals. In recent years, many models have been developed to optimize the CL process considering the perspectives of the different stakeholders involved. Studies mainly focus on the location and role of distribution warehouses, freight flows, the routing task, vehicle loading, the size and type of vehicles that can enter urban areas, and possible charges for accessing city centers. However, a successful implementation of such models requires internal efficiency by each actor. In this context, a crucial role is played by logistics service providers (LSPs) because they are expected to offer high quality services in congested urban areas and the effectiveness of their activities depends on the interactions among all the CL stakeholders. The paper proposes an empirical analysis on the operational factors determining the level of efficiency of a LSP. Based on the analysis of literature, the efficiency is here assessed through productivity, which in turn is measured as the number of stops that a driver daily makes during his service. Data about a LSP involved in urban freight distribution in Italy are analyzed and a regression analysis is completed. Results highlight that two managerial levers affect the level of productivity. The first one is related to the organization of the distribution network: a more efficient location of warehouses, an extension of the area covered by each driver and a more efficient routing structure can significantly increase the productivity of a LSP. At the same time, the vehicle loading strategy appears to be crucial: as a matter of fact, vehicles should not be excessively loaded, especially with big parcels, so that the business can be performed more efficiently. This study represents an attempt to develop a comprehensive panel of operational variables that support the efficiency of the urban distribution system of LSPs. The potential benefits associated with the enhancement of efficiency are both economic and environmenta

Investigating Fine Temporal Dynamics of Prosodic and Lexical Accommodation

Conversational interaction is a dynamic activity in which participants engage in the construction of meaning and in establishing and maintaining social relationships. Lexical and prosodic accommodation have been observed in many studies as contributing importantly to these dimensions of social interaction. However, while previous works have considered accommodation mechanisms at global levels (for whole conversations, halves and thirds of conversations), this work investigates their evolution through repeated analysis at time intervals of increasing granularity to analyze the dynamics of alignment in a spoken language corpus. Results show that the levels of both prosodic and lexical accommodation fluctuate several times over the course of a conversation

The BIM towards the Cadastre of the Future enhanced through the Use of Technology / Il BIM verso il Catasto del Futuropotenziato tramite l’utilizzo della tecnologia

Knowing, digitalizing, sharing represent the key concepts of this millennium. The construction and Real Estate sectors have the opportunity to take up this challenge by becoming promoters of intelligent data management that characterize buildings. The Buil-ding Information Modelling (BIM) methodology, strengthened by the unstoppable technological progress, lays the groundwork for re-designing a structured knowledge system of the building heritage. This triggers a new concept of Cadastre of the Future, dynamic and updated, which interrogates the Big Data of the buildings according to a multidisciplinary and interoperable approach. The perspective is ambitious, but it is essential to define the correct methodological approach to govern the digitization of built herita-ge. The setting up of the first experimentations is carried out on the City of Turin. Pursuing the vision of augmented digital city, an interactive map has been created, exploiting new technologies, such as Augmented and Virtual Reality, to enable the dissemination of information to different types of users. / Conoscere, digitalizzare, condividere rappresentano i concetti chiave di questo millennio. Il settore delle costruzioni e del Real Esta-te hanno l’opportunità di cogliere questa sfida, diventando promotori di una gestione intelligente dei dati che caratterizzano gli edifici. La metodologia del Building Information Modeling (BIM), rafforzata dall’inarrestabile progresso tecnologico, pone le basi per riprogettare un sistema conoscitivo strutturato del patrimonio edilizio, innescando una nuova concezione di Catasto del Futuro, dinamico e aggiornato, che interroga i Big Data degli edifici secondo un approccio multidisciplinare e interoperabile. La prospettiva è ambiziosa, ma è essenziale definire il corretto approccio metodologico per governare la digitalizzazione del costruito. La messa a sistema delle prime sperimentazioni è condotta sulla città di Torino, dove, perseguendo la visione di città digitale aumentata, è stata realizzata una mappa interattiva che sfrutta le nuove tecnologie, quali la Realtà Aumentata e la Realtà Virtuale, per consentire la diffusione delle informazioni a differenti tipologie di utenti

Emergence of collective self-oscillations in minimal lattice models with feedback

The emergence of collective oscillations and synchronization is a widespread phenomenon in complex systems. While widely studied in dynamical systems theory, this phenomenon is not well understood in the context of out-of-equilibrium phase transitions. Here we consider classical lattice models, namely the Ising, the Blume-Capel and the Potts models, with a feedback among the order and control parameters. With linear response theory we derive low-dimensional dynamical systems for mean field cases that quantitatively reproduce many-body stochastic simulations. In general, we find that the usual equilibrium phase transitions are taken over by complex bifurcations where self-oscillations emerge, a behavior that we illustrate by the feedback Landau theory. For the case of the Ising model, we obtain that the bifurcation that takes over the critical point is non-trivial in finite dimensions. We provide numerical evidence that in 2D the most probable value of the amplitude follows the Onsager law. We illustrate multi-stability for the case of discontinuously emerging oscillations in the Blume-Capel model, whose tricritical point is substituted by the Bautin bifurcation. For the Potts model with q = 3 colors we highlight the appearance of two mirror stable limit cycles at a bifurcation line and characterize the onset of chaotic oscillations that emerge at low temperature through either the Feigenbaum cascade of period doubling or the Aifraimovich-Shilnikov scenario of a torus destruction. We show that entropy production singularities as a function of the temperature correspond to change in the spectrum of Lyapunov exponents. Our results show that mean-field behaviour can be described by the bifurcation theory of low-dimensional dynamical systems, which paves the way for the definition of universality classes of collective oscillations.Comment: 25 pages 10 figure

Influence of arbuscular mycorrhizae on plant growth, essential oil production and phosphorus uptake of Salvia officinalis L

Arbuscular mycorrhiza fungi (AMF) contribute to the secondary metabolism and production of active ingredients in aromatic and medicinal plants. This symbiotic association is particularly affected by the availability of phosphorus (P) in the soil. This study was conducted on Salvia officinalis L. using two inocula, commercial Symbivit and Septoglomus viscosum (syn. Glomus viscosum), alone or supplemented with two doses of actual P (0.03, 0.06 g kg−1). The effects of these fungi and their combinations with P were determined in relation to the growth of sage plants (Regula variety), to the concentration of P in leaf tissues, and to the quantity and quality of essential oils (EOs). S. viscosum treated plants showed better growth with or without P-supply compared to non-mycorrhizal plants. The plants inoculated with S. viscosum presented the highest dry weight regardless of addition of P. Both AM fungi increased the leaf P content as more P was applied to the soil, whereas the EO content did not change with any of the treatments. Although the EO yield slightly increased with the Symbivit treatment, the chemical composition of the oil was drastically altered by S. viscosum in which the manool was the main component (28.13%), while -thujone decreased (13.09%). These results suggest that AM symbiosis is a good candidate for promoting plant growth and essential oil composition and for improving P uptake in low fertility soils. Thus, mycorrhiza can be considered as a sustainable strategy based on natural resources in order to influence the manool and -thujone content in sage EO composition. These compositions are very important to develop new classes of biocides and contribute to reducing risks to both human health and the environment

Factor influencing Logistics Service Providers Efficiency’ in Urban Distribution Systems

The increased urbanization and the awareness of freight transportation impacts have stressed the importance of City Logistics (CL) as a comprehensive approach aimed at mitigating the negati ve effects of distribution activities without penalizing social, cultural, and economic issues. In this context, a crucial role is played by logistics service providers (LSPs) . This paper propo ses an empirical analysis on the operational factors determining the level of efficiency of a LSP. This study represents an attempt to develop a panel of operational variables supporting the efficiency of the urban distribution system of LSPs. The potential benefits are both economic and environmental

Asymmetric Contributions of the Fronto-Parietal Network to Emotional Conflict in the Word–Face Interference Task

The fronto-parietal network is involved in top-down and bottom-up processes necessary to achieve cognitive control. We investigated the role of asymmetric enhancement of the left dorsolateral prefrontal cortex (lDLPFC) and right posterior parietal cortex (rPPC) in cognitive control under conditions of emotional conflict arising from emotional distractors. The effects of anodal tDCS over the lDLPFC/cathodal over the rPPC and the effects of anodal tDCS over the rPPC/cathodal over the lDLPFC were compared to sham tDCS in a double-blind design. The findings showed that anodal stimulation over the lDLPFC reduced interference from emotional distractors, but only when participants had already gained experience with the task. In contrast, having already performed the task only eliminated facilitation effects for positive stimuli. Importantly, anodal stimulation of the rPPC did not affect distractors’ interference. Therefore, the present findings indicate that the lDLPFC plays a crucial role in implementing top-down control to resolve emotional conflict, but that experience with the task is necessary to reveal this role