Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223

Objective: Androgen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223. Patients and methods: Low-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded. Results: SM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis. Conclusion: The present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223. Graphical abstract: [Figure not available: see fulltext.

Stereotactic radiotherapy for ultra-central lung oligometastases in non-small-cell lung cancer

Background: Stereotactic body radiotherapy (SBRT) in ultra-central (UC) lung tumors, defined in the presence of planning target volume (PTV) overlap or direct tumor abutment to the central bronchial tree or esophagus, may be correlated to a higher incidence of severe adverse events. Outcome and toxicity in oligometastatic (≤3 metastases) non-small-cell lung cancer (NSCLC) patients receiving SBRT for UC tumors were evaluated. Methods: Oligometastatic NSCLC patients treated with SBRT for UC were retrospectively reviewed. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were calculated. Incidence and grade of toxicity were evaluated. Statistical analysis was performed to assess the impact of clinical and treatment-related variables on outcome and toxicity occurrence. Results: Seventy-two patients were treated to a median biologically effective dose (BED) of 105 (75–132) Gy10 . Two-year LC, DMFS, PFS, and OS were 83%, 46%, 43%, and 49%. BED>75 Gy10 was correlated to superior LC (p = 0.02), PFS (p = 0.036), and OS (p < 0.001). Grade ≥3 toxicity rate was 7%, including one fatal esophagitis. No variables were correlated to DMFS or to occurrence of overall and grade ≥3 toxicity. Conclusions: SBRT using dose-intensive schedules improves outcome in NSCLC patients. Overall toxicity is acceptable, although rare but potentially fatal toxicities may occur

Parallel symbolic state-space exploration is difficult, but what is the alternative?

State-space exploration is an essential step in many modeling and analysis problems. Its goal is to find the states reachable from the initial state of a discrete-state model described. The state space can used to answer important questions, e.g., "Is there a dead state?" and "Can N become negative?", or as a starting point for sophisticated investigations expressed in temporal logic. Unfortunately, the state space is often so large that ordinary explicit data structures and sequential algorithms cannot cope, prompting the exploration of (1) parallel approaches using multiple processors, from simple workstation networks to shared-memory supercomputers, to satisfy large memory and runtime requirements and (2) symbolic approaches using decision diagrams to encode the large structured sets and relations manipulated during state-space generation. Both approaches have merits and limitations. Parallel explicit state-space generation is challenging, but almost linear speedup can be achieved; however, the analysis is ultimately limited by the memory and processors available. Symbolic methods are a heuristic that can efficiently encode many, but not all, functions over a structured and exponentially large domain; here the pitfalls are subtler: their performance varies widely depending on the class of decision diagram chosen, the state variable order, and obscure algorithmic parameters. As symbolic approaches are often much more efficient than explicit ones for many practical models, we argue for the need to parallelize symbolic state-space generation algorithms, so that we can realize the advantage of both approaches. This is a challenging endeavor, as the most efficient symbolic algorithm, Saturation, is inherently sequential. We conclude by discussing challenges, efforts, and promising directions toward this goal

Elasticity and Petri nets

Digital electronic systems typically use synchronous clocks and primarily assume fixed duration of their operations to simplify the design process. Time elastic systems can be constructed either by replacing the clock with communication handshakes (asynchronous version) or by augmenting the clock with a synchronous version of a handshake (synchronous version). Time elastic systems can tolerate static and dynamic changes in delays (asynchronous case) or latencies (synchronous case) of operations that can be used for modularity, ease of reuse and better power-delay trade-off. This paper describes methods for the modeling, performance analysis and optimization of elastic systems using Marked Graphs and their extensions capable of describing behavior with early evaluation. The paper uses synchronous elastic systems (aka latency-tolerant systems) for illustrating the use of Petri nets, however, most of the methods can be applied without changes (except changing the delay model associated with events of the system) to asynchronous elastic systems.Peer ReviewedPostprint (author's final draft

PEPA Nets

In this chapter we describe a formalism which uses the stochastic process algebra PEPA as the inscription language for labelled stochastic Petri nets. Viewed in another way, the net is used to provide a structure for linking related PEPA systems. The combined modelling language naturally represents such applications as mobile code systems where the PEPA terms are used to model the program code which moves between network hosts (the places in the net). We demonstrate the modelling capabilities of the formalism on a number of examples, including a mobile server running MobileIP

A preliminary dictionary of Maori gainwords compiled on historical principles

This thesis is a preliminary dictionary of Maori gainwords compiled on historical principles. It will serve as the starting point for a fully fledged historical dictionary of Maori gainwords. The sources are a selection of all those Maori language publications printed between the dates 1815 and 1899. A large number of source items were photocopied from other institutions, and the binding and subsequent availability of these was not always in the order wished for. The research therefore has its limitations (clearly indicated by the use of the word 'preliminary' in the thesis title). Full coverage of all printed Maori publications between 1815 and 1899 has not been possible. Despite this, this preliminary dictionary offers a good indication of the extent of new gainword vocabulary introduced within the time frame. This thesis suggests that the terms loanword and borrowing should be replaced by the new term gainword or gain, and that the process by which new items of vocabulary enter a language should be known as gaining .. 'Gaining' is a positive process, and the word 'gainword' is normally devoid of any negative connotations or implications of cultural imperialism. This thesis is the first extended scholarly research into Maori gainword lexicography. Although 'preliminary', the dictionary is the first devoted solely to Maori gainwords - previous dictionaries of Maori have had gainwords as appendices, or have listed small numbers of gainwords in their general corpus. This dictionary builds on those earlier dictionaries by giving gainwords their own dictionary. This thesis will indicate that nearly all new items of vocabulary introduced into Maori language during the period researched were introduced by English-speaking Pakeha. English-speaking (and some few French-speaking) Pakeha controlled the printed word for some considerable time - up until the first Maori-controlled publication, Te Hokioi in 1861, in fact most gainwords were therefore imposed. The frequency count for Maori-driven gains done for this thesis will give only some slight indication of Maori use and acceptance of gains between 1815 and 1899