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Automated planning technology now plays a significant role in a variety of demanding applications, ranging from controlling space vehicles and robots to playing the game of bridge. These real-world applications create new opportunities for synergy between theory and practice: observing what works well in practice leads to better theories of planning, and better theories lead to better performance of practical applications. Automated Planning mirrors this dialogue by offering a comprehensive, up-to-date resource on both the theory and practice of automated planning. The book goes well beyond classical planning, to include temporal planning, resource scheduling, planning under uncertainty, and modern techniques for plan generation, such as task decomposition, propositional satisfiability, constraint satisfaction, and model checking. The authors combine over 30 years experience in planning research and development to offer an invaluable text to researchers, professionals, and graduate students. *Comprehensively explains paradigms for automated planning. *Provides a thorough understanding of theory and planning practice, and how they relate to each other. *Presents case studies of applications in space, robotics, CAD/CAM, process control, emergency operations, and games. *Provides a thorough understanding of AI planning theory and practice, and how they relate to each other. *Covers all the contemporary topics of planning, as well as important practical applications of planning, such as model checking and game playing. *Presents case studies and applications in planning engineering, space, robotics, CAD/CAM, process control, emergency operations, and games.*Provides lecture notes, examples of programming assignments, pointers to downloadable planning systems and related information online.

3D models have been introduced as tools to improve surgeon's precision during Robotic-Assisted Partial Nephrectomy (RAPN). They showed to provide accurate anatomical details, improve operative time and patient safety by reducing complications. Over the last years, several useful models have been developed and proposed. However, literature is still scant regarding if and how the experience of the operator, and the learning curve, may impact the accuracy and precision of the model. In this light, the aim of the study is to evaluate the accuracy, the interpersonal variability of the precision and the learning curve for the segmentation of RAPN 3D preoperative models starting from CT images. This study will identify the influence of operator experience and learning curves on the accuracy of 3D preoperative models in RAPN, optimizing workflows for broader clinical adoption.

The contact surface area (CSA) quantifies the interface between a tumor and an organ and is a key predictor of perioperative outcomes in kidney cancer. However, existing CSA computation methods rely on shape assumptions and manual annotation. We propose a novel approach using 3D reconstructions from computed tomography (CT) scans to provide an accurate CSA estimate. Our method includes a segmentation protocol and an algorithm that processes reconstructed meshes. We also provide an open-source implementation with a graphical user interface. Tested on synthetic data, the algorithm showed minimal error and was evaluated on data from 82 patients. We computed the CSA using both our approach and Hsieh’s method, which relies on subjective CT scan measurements, in a double-blind study with two radiologists of different experience levels. We assessed the correlation between our approach and the expert radiologist’s measurements, as well as the deviation of both our method and the less experienced radiologist from the expert’s values. While the mean and variance of the differences between the less experienced radiologist and the expert were lower, our method exhibited a slight deviation from the expert’s, demonstrating its reliability and consistency. These findings are further supported by the results obtained from synthetic data testing.

The World Health Organization’s strategic plan for 2012-2020 for schistosomiasis is aimed at controlling morbidity by 2020, eliminating SH infection as a public health problem, and interrupting transmission in select areas by 2025.

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13–38.00 vs. 40.93 months, 95% CI: 40.93–40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the “tip of the iceberg”, by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT.

Automated planning technology now plays a significant role in a variety of demanding applications, ranging from controlling space vehicles and robots to playing the game of bridge. These real-world applications create new opportunities for synergy between theory and practice: observing what works well in practice leads to better theories of planning, and better theories lead to better performance of practical applications.

Background Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod. Objective The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints. Experimental design GX301 was administered by intradermally injecting 500 μg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization. Results No grade 3–4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses. Conclusion GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.

CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25 hi Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25 hi Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+ Treg (both from peripheral blood and tumor microenvironment) suggesting that CD39-mediated inhibition constitutes a prevalent hallmark of their function. Collectively, these findings, unveiling a new mechanism of action for CD8+ Treg, provide new knowledge on intratumoral molecular pathways related to tumor immune escape, which could be exploited in the future for designing new biological tools for anticancer immune intervention.

Testosterone promotes apoptotic damage in human renal tubular cells. Apoptosis is a mode of cell death that participates in the kidney physiologic remodeling processes and is thought to contribute to cell loss and kidney structural damage in chronic renal diseases. Gender is one factor which contributes to accelerated nephron loss, with progression more rapid in men than in women in diabetic and nondiabetic chronic renal diseases. Mechanisms by which androgens may cause higher rate of progression of chronic renal diseases in men are poorly explored. In this study, to investigate the role of androgens on apoptotic damage and its associated mechanisms, we examined the effects of testosterone (T) (0.1nmol/L to 1 μmol/L) on apoptosis, and apoptosis-related proteins in a proximal human tubule cell line (HK-2 cells). Additional experiments were performed in primary cultures of proximal tubular epithelial cells (PTECs). Cells were grown to subconfluence in normal growth medium, and apoptotic damage was induced by serum deprivation for 24 to 48hours. Cycloheximide, flutamide (a T-receptor antagonist), 17-β estradiol, or caspase inhibitors were added to cultures that were successively processed for terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end-labeling (TUNEL) analysis, annexin V/propidium iodide staining, immunofluorescence, or immunoblots to identify effects and apoptotic pathways that could be modulating cell survival. Both morphologic analysis by annexin V/propidium iodide staining and TUNEL showed that physiologic T levels (1 to 10nmol/L) induced a significant increase in apoptosis both in HK-2 cells and PTECs. In both types of cell lines pretreatment with the androgen receptor antagonist flutamide prevented the T-induced apoptosis. T-induced apoptosis was enhanced by treatment with cycloheximide and prevented by 17β-estradiol. Fas, Fas ligand (FasL), and Fas-associating death domain containing protein (FADD) were clearly up-regulated within 48hours of T treatment in HK-2 cells. Also, T significantly increased the expression of Bax protein (P < 0.01 vs. control) (an effect which was blocked by flutamide), and decreased the expression of Bcl-2. Western blot analysis showed that caspase-3 was activated. Moreover, cleavage into an 85-kD poly(ADP-ribose) polymerase-1 (PARP-1) terminal breakdown product was detectable. The changes in cellular morphology induced by T at 48hours were no longer observed after the addition of caspase-8, caspase-9, and caspase-3 inhibitors to the culture medium. These results indicate that T increases the permissiveness of proximal tubule kidney cells to apoptotic effects by triggering an apoptotic pathway involving caspase activation, Fas up-regulation, and FasL expression, thus potentially interacting with mechanisms of cell loss which have been already shown to be activated in chronic renal diseases. This is consistent with a role for T in promoting renal injury in men.

We present a framework that supports the formal verification of early requirements specifications. The framework is based on< Formal Tropos<, a specification language that adopts primitive concepts for modeling early requirements (such as actor, goal, and strategic dependency), along with a rich temporal specification language. We show how existing formal analysis techniques, and in particular< model checking<, can be adapted for the automatic verification of Formal Tropos specifications. These techniques have been implemented in a tool, called the T-Tool, that maps Formal Tropos specifications into a language that can be handled by the NuSMV model checker. Finally, we evaluate our methodology on a course-exam management case study. Our experiments show that formal analysis reveals gaps and inconsistencies in early requirements specifications that are by no means trivial to discover without the help of formal analysis tools.