Long term survival of HER2-positive early breast cancer treated with trastuzumab-based adjuvant regimen: A large cohort study from clinical practice

Abstract Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006–2009). DFS and OS were estimated using the Kaplan–Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were ag

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

The DUNE far detector vertical drift technology. Technical design report

DUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

Consensus problem in nonlinear spaces

The thesis studies the problem of consensus, considering a set of N agents locally exchanging information about their state in order to asymptotically reach a common value of agreement: a global consensus. Chapter 2 is devoted to recalling some mathematical preliminaries, such as concepts of stability, Lyapunov theory, graph theory; this chapter also gives some (intuitive) notions of critical concepts concerning nonlinear spaces (e.g. the concept of manifold, geodesic and geodesic distance, Lie group). Chapter 3 deals with the goal of the thesis: the consensus; firstly we introduce the problem in linear space and then in nonlinear spaces, focusing our attention on the circle. A natural adaptation of linear consensus on the circle is, in fact, the celebrated Kuramoto model. In Chapter 4 we give some critical examples of application of consensus both in biological (e.g. flashing fireflies) and engineering problems (e.g. AOSN, vehicle formations

Online multimodal autonomous learning of robots internal models

Robots can learn new skills by autonomously acquiring internal models that can be used for action planning and control. The ability of learning internal models with no prior information allows robots to be fully autonomous not only in the acquisition of such models and motor skills, but also in adapting to new environments and working set-ups. This is particularly important for robots interacting with humans in unconstrained environments. Autonomous learning eases the engineering work of pre-programming each robotic system for each particular task, while endowing robots with flexibility, adaptability and versatility. This thesis investigates how the use of multiple sources of information can influence such autonomous learning process. In particular, multiple prediction hypotheses provided by different prediction models, as well as information available to a robot from multiple sensory modalities (such as vision, touch, proprioception) are leveraged to enhance the learning process. Through autonomous exploration a robot can bootstrap internal models of its own sensorimotor system that enable it to predict the consequences of its actions (forward models) or to generate new actions to reach target states (inverse models). This thesis studies how multiple information can enhance the bootstrapping process of these models or their use in environments and tasks that involve integration of different types of data. It is shown that the use of multiple sources of information benefits the learning process. The combination of multiple predictors allows to enhance forward models' accuracy. The use of multiple sensory modalities is fundamental to perform tasks that are inherently multimodal, such as playing a piano keyboard. Also, multimodal integration allows a versatile applicability of the model learned. Furthermore, the learned multimodal model can be deployed in learning and control frameworks to predict the robot and other agents' motion, and to plan the robot's actions.Open Acces