A tribute to Juan Rosai

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Diagnostica cito-istologica dei noduli tiroidei:uno studio multicentrico

La citologia agoaspirativa con ago sottile (FNA) rappresenta uno strumento diagnostico fondamentale nella gestione clinica dei pazienti con noduli tiroidei. Tuttavia, come dimostrato dai dati della letteratura, quest’ultima mostra una performance diagnostica molto variabile ed è gravata da una percentuale di falsi negativi pari al 7%. Altro limite ben noto di questa metodica è l’elevata percentuale (24%) di FNAs con risultato indeterminato, il 70%-80% dei quali, risulta essere benigno all’esame istologico post-operatorio. Abbiamo quindi intrapreso uno studio con lo scopo di sviluppare un test molecolare per migliorare la gestione clinica di questi pazienti. Nel collezionare tale materiale agoaspirativo e nell’analizzare i dati clinici associati abbiamo perseguito un triplice scopo: - Correlare i risultati citologici ed istologici per valutare la performance diagnostica della citologia agoaspirativa dei noduli tiroidei (senisibilita’, specificità, valore predittivo positivo e valore predittivo negativo) in uno studio di tipo prospettico. - Condurre una meta-analisi aggiornata della letteratura e comparare i dati così ottenuti con i nostri. - Confrontare le diagnosi istologiche effettuate da un panel di anatomopatologi di riferimento con quelle formulate dai patologi locali. Materiali e metodi Performance diagnostica. Il materiale agoaspirativo selezionato da vari centri è stato diviso in due gruppi: - Gruppo A : materiale prospettico. FNAs provenienti da 21 cliniche (16 statunitensi-non accademiche, 3 statunitensi-accademiche, 2 accademiche non-statunitensi), in un periodo compreso tra agosto 2008-gennaio 2010. - Gruppo B: materiale retrospettivo. FNAs proveniente dagli archivi di 2 cliniche accademiche. Le diagnosi citologiche (gruppo A) sono quindi state comparate con le diagnosi istologiche formulate dai patologi locali al fine di valutarne la perfomance diagnostica (sensibilita’ specificità, valore predittivo positivo valore predittivo negativo e percentuale di falsi negativi) Concordanza diagnostica. Una parte dei preparati istologici e’ stata revisionata da due anatomopatologi di riferimento, il prof. Juan Rosai e la prof.ssa Virginia LiVolsi. I un primo momento, ogni esperto ha revisionato i casi indipendentemente, ovvero all’oscuro della diagnosi formulate dal patologo locale e dell’opinione dell’altro esperto. Successivamente i due patologi esperti hanno avuto la possibilità di discutere i casi nei quali vi era disaccordo, al fine di raggiungere una diagnosi di consenso. E’ stato quindi possibile valutare la concordanza diagnostica tra esperti e tra esperti vs patologi locali. Metanalisi della lettera Sono stati selezionati dalla letteratura studi incentrati sul confronto cito-istologico nella diagnostica tiroidea e che rispondessero ai seguenti criteri: • Lo studio doveva essere condotto sulla popolazione statunitense. • I prelievi dei noduli non palpabili dovevano essere eseguiti sotto guida ecografica. • Lo studio doveva includere più di 150 controlli chirurgici. I vari studi sono stati divisi in accademici e non-accademici in base all’istituto di provenienza. Risultati Sono stati selezionati 1501 campioni citologici (gruppo A + gruppo B) ottenuti da 1285 pazienti con età compresa tra i 18-94 anni (età media = 52 anni), l’85% dei quali di sesso femminile. 606 esami citologici (gruppo A + gruppo B) avevano un controllo istologico e di questi , 221 sono stati rivalutati dai 2 anatomopatologi esperti. Dei 1501 campioni citologici, 753 (613 pazienti ) appartiene al gruppo A (studio prospettico). Circa il 99% delle FNAs sono state eseguite sotto guida ecografica. La performance diagnostica della citologia agoaspirativa tiroidea ottenuta sul nostro materiale è risultata comparabile con quando osservato nella meta-analisi della letteratura. In particolare le percentuali di noduli maligni all’esame istologico tra i citologici “indeterminati” e “maligni” è risultata essere rispettivamente del 34% e 98% quindi sovrapponibile a quanto osservato nella meta-analisi della letteratura (rispettivamente 34% e 98%). Per quanto riguarda il tasso di malignità tra i citologici benigni abbiamo osservato una percentuale di falsi negativi maggiore tra i nostri agoaspirati rispetto alla meta-analisi della letteratura (11% vs 6%). Nell’ambito dell’analisi falsi negativi riscontrati in letteratura, abbiamo inoltre osservato una percentuale differente tra gli studi effettuati presso centri accademici rispetto ai centri non-accademici (2% vs 10%). Anche le percentuali di agoaspirati per ogni categoria diagnostica citologica, osservate nello studio prospettico (gruppo A), sono risultate simili a quanto osservato nella meta-analisi. La percentuale di discordanza diagnostica istologica (benigno vs maligno) è risultata maggiore nel confronto tra patologi locali vs diagnosi di consenso degli esperti (11%) rispetto a quanto osservato tra esperti sia pre- (8%) che post-confronto (3%). Conclusioni La percentuale post-operatoria di malignità osservata nel nostro studio è paragonabile a quanto osservato nella meta-analisi della letteratura. Quindi, sebbene le recenti linee guida abbiano cercato di standardizzare ed ottimizzare la tecnica di esecuzione e di interpretazione degli FNA tiroidei i risultati falsamente positivi e falsamente negativi rimangono un problema irrisolto. Inoltre, l’elevato numero di citologici indeterminati con diagnosi istologica di patologia benigna (66%), pone un interrogativo sulla corretta gestione clinica di questi pazienti. Data la variabilità osservata nel formulare le diagnosi istologiche, nuovi test molecolari sviluppati con l’intento di migliorare la gestione clinica dei pazienti con patologia tiroidea, dovranno comprendere nella loro elaborazione la revisione istologica da parte di esperti in patologia tiroidea

The Stellar decomposition: A compact representation for simplicial complexes and beyond

We introduce the Stellar decomposition, a model for efficient topological data structures over a broad range of simplicial and cell complexes. A Stellar decomposition of a complex is a collection of regions indexing the complex’s vertices and cells such that each region has sufficient information to locally reconstruct the star of its vertices, i.e., the cells incident in the region’s vertices. Stellar decompositions are general in that they can compactly represent and efficiently traverse arbitrary complexes with a manifold or non-manifold domain. They are scalable to complexes in high dimension and of large size, and they enable users to easily construct tailored application-dependent data structures using a fraction of the memory required by a corresponding global topological data structure on the complex. As a concrete realization of this model for spatially embedded complexes, we introduce the Stellar tree, which combines a nested spatial tree with a simple tuning parameter to control the number of vertices in a region. Stellar trees exploit the complex’s spatial locality by reordering vertex and cell indices according to the spatial decomposition and by compressing sequential ranges of indices. Stellar trees are competitive with state-of-the-art topological data structures for manifold simplicial complexes and offer significant improvements for cell complexes and non-manifold simplicial complexes. We conclude with a high-level description of several mesh processing and analysis applications that utilize Stellar trees to process large datasets

Robotic Heller-Dor myotomy: 10-year monocentric experience compared with POEM

Achalasia is a rare motility disorder caused by an incomplete relaxation of the lower esophageal sphincter and loss of esophageal peristalsis. As a consequence, the bolus swallowing is hindered and the patients complain dysphagia, regurgitation, chest pain, respiratory symptoms and weight loss. Achalasia’s treatment has been varied over time, from therapies aiming to relax the lower sphincter of the esophagus, including drugs andBotox injection or mechanical dilatations, to surgical myotomy. Robotic or laparoscopic Heller-Dor procedure is considered the gold standard surgical treatment for symptomatic achalasia as it is proved to be effective and safe. As an alternative, Per-Oral Endoscopic Myotomy (POEM) was applied over the past decade, aiming to combine the same results of mini-invasive procedure to the advantages of endoscopic approach. In this study, we are going to compare the medium-long term results of mini-invasive Heller-Dor procedure, routinely performed in our Department, with those of POEM reported in literature

TopoCluster: A Localized Data Structure for Topology-based Visualization

Unstructured data are collections of points with irregular topology, often represented through simplicial meshes, such as triangle and tetrahedral meshes. Whenever possible such representations are avoided in visualization since they are computationally demanding if compared with regular grids. In this work, we aim at simplifying the encoding and processing of simplicial meshes. The paper proposes TopoCluster, a new localized data structure for tetrahedral meshes. TopoCluster provides efficient computation of the connectivity of the mesh elements with a low memory footprint. The key idea of TopoCluster is to subdivide the simplicial mesh into clusters. Then, the connectivity information is computed locally for each cluster and discarded when it is no longer needed. We define two instances of TopoCluster. The first instance prioritizes time efficiency and provides only a modest savings in memory, while the second instance drastically reduces memory consumption up to an order of magnitude with respect to comparable data structures. Thanks to the simple interface provided by TopoCluster, we have been able to integrate both data structures into the existing Topological Toolkit (TTK) framework. As a result, users can run any plugin of TTK using TopoCluster without changing a single line of code

Interactive visualization and topology-based analysis of large-scale time-varying remote-sensing data: challenges and opportunities

Over the last few years, the amount of large and complex data in the public domain has increased enormously and new challenges arose in the representation, analysis and visualization of such data. Considering the number of space missions that provided and will provide remote sensing data, there is still the need of a system that can be dispatched in several remote repositories and being accessible from a single client of commodity hardware. To tackle this challenge, at the DLR Institute for Software Technology we have defined a dual backend frontend system, enabling the interactive analysis and visualization of large-scale remote sensing data. The basis for all visualization and interaction approaches is CosmoScout VR, a visualization tool developed internally at DLR, and publicly available on Github, that allows the visualization of complex planetary data and large simulation data in real-time. The dual component of this system is based on an MPI framework, called Viracocha, that enables the analysis of large data remotely, and allows the efficient network usage about sending compact and partial results for interactive visualization in CosmoScout as soon as they are computed. A node-based interface is defined within the visualization tool, and this lets a domain expert to easily define customized pipelines for processing and visualizing the remote data. Each “node” of this interface is either linked with a feature extraction module, defined in Viracocha, or to a rendering module defined directly in CosmoScout. Being this interface completely customizable by a user, multiple pipelines can be defined over the same dataset to enhance even more the visualization feedback for analysis purposes. Being an ongoing project, on top of these tools, as a novel strategy in EO data processing and visualization, we plan to define and implement strategies based on Topological Data Analysis (TDA). TDA is an emerging set of technique for processing the data considering its topological features. These include both the geometric information associated to a point, as well all the non-geometric scalar values, like temperature and pressure, to name a few, that can be captured during a monitoring mission. One of the major theories behind TDA is Discrete Morse Theory, that, given a scalar value, is used to define a gradient on such function, extract the critical points, identify the region-of-influence of each critical point, and so on. This strategy is parameter free and enables a domain scientist to process large datasets without a prior knowledge of it. An interesting research question, that it will be investigated during this project is the correlation of changes of critical points at different time steps, and the identification of deformation (or changes) across time in the original dataset

Efficient topology-aware simplification of large triangulated terrains

A common first step in the terrain processing pipeline of large Triangulated Irregular Networks (TINs) is simplifying the TIN to make it manageable for further processing. The major problem with TIN simplification algorithms is that they create or remove critical points in an uncontrolled way. Topology-aware operators have been defined to solve this issue by coarsening a TIN without affecting the topology of its underlying terrain, i.e., without modifying critical simplices describing pits, saddles, peaks, and their connectivity. While effective, existing algorithms are sequential in nature and are not scalable enough to perform well with large terrains on multicore systems. Here, we consider the problem of topology-aware simplification of very large meshes. We define a topology-aware simplification algorithm on a compact and distributed data structure for triangle meshes, namely the Terrain trees. Terrain trees reduce both the memory and time requirements of the simplification procedure by adopting a batched processing strategy of the mesh elements. Furthermore, we define a new parallel topology-aware simplification algorithm that takes advantage of the spatial domain decomposition at the basis of Terrain trees. Scalability and efficiency are experimentally demonstrated on real-world TINs originated from topographic and bathymetric LiDAR data. Our experiments show that topology-aware simplification on Terrain trees uses 40% less memory and half the time than the same approach implemented on the most compact and efficient connectivity-based data structure for TINs. Beyond that, our parallel algorithm on the Terrain trees reaches a 12x speedup when using 20 threads

Optoacoustic solitons in Bragg gratings

Optical gap solitons, which exist due to a balance of nonlinearity and dispersion due to a Bragg grating, can couple to acoustic waves through electrostriction. This gives rise to a new species of ``gap-acoustic'' solitons (GASs), for which we find exact analytic solutions. The GAS consists of an optical pulse similar to the optical gap soliton, dressed by an accompanying phonon pulse. Close to the speed of sound, the phonon component is large. In subsonic (supersonic) solitons, the phonon pulse is a positive (negative) density variation. Coupling to the acoustic field damps the solitons' oscillatory instability, and gives rise to a distinct instability for supersonic solitons, which may make the GAS decelerate and change direction, ultimately making the soliton subsonic.Comment: 5 pages, 3 figure

Firm Survival: An Empirical Study Concerning Insurance Agencies

This paper analyzes the relevance of firm size, region, sales network, organizational structure, and auditing on the survival likelihood of a specific firm typology, the insurance agency. By applying a configurational comparative method, namely fuzzy-set qualitative analysis (fsQCA), to a unique dataset of 52 insurance agents, representing 52 active Italian insurance agencies, this study demonstrates that, when combined with other variables, organizational structure provides sufficient conditions for insurance agency survival. The different relevance of some specific management areas according to the insurance agency location is highlighted