Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. � 2016 Michal Lotem et al

Graphemic puns, and software making them up: The case of Hebrew vs Chinese and Japanese

Yaakov HaCohen-Kerner, Daniel Nisim Cohen, Ephraim Nissan and Ghil'ad Zuckerman

Classification of lymphoproliferative disorders by spectral imaging of the nucleus

Spectral nuclear morphometry was used for the classification of lymphocytes in lymphoproliferative disorders. May-Grunwald-Giemsa-stained blood specimens were taken from thirty patients with infectious mononucleosis, non-Hodgkin lymphoma or chronic lymphocytic leukemia, and from ten healthy individuals. Blood specimens were analyzed by spectral imaging. Seventeen distinct spectra were collected into a spectral library and a distinct pseudo color was assigned to each one of them. The library was used to scan all the cells in the database and to create a spectrally classified image of each cell. The spectral map, per cell, reveals distinct spectral-response regions in each cellular compartment, via the distinct region colors. Computational analysis of the spectral maps allows for the objective quantification of a set of parameters, or features, representing the cell. The features used in this work include the area and perimeter of the nucleus, circularity, edginess and the spectral pattern. The analysis pursued showed that each class of cells is associated with a set of unique parameters. We conclude that spectral analysis combined with feature analysis provides significant information in the analysis of lymphoproliferative disorders and may serve as an additional tool for the histopathological evaluation of disease

A Quarter of Century in Artificial Intelligence and Law: Projects, Personal Trajectories, a Subjective PerspectiveLanguage, Culture, Computation. Computing of the Humanities, Law, and Narratives

This article describes projects in the domain of artificial intelligence and law, which resulted from the research of the five authors listed, when they formed teams (of the first author named and each one of the other authors). Therefore, the present paper offers a subjective perspective, from the viewpoint of personal trajectories within AI & Law. Several, though not all, of the projects concerned dealt with facets of legal evidence. These projects include: ALIBI (an AI planner generating exonerating accounts); a representation of Italy’s regional constitutions in a nested-relation representation (a precursor of XML); the application of kappa calculus and a probabilistic interpretation to a Scandinavian approach to evidential strength; the application of Petri Nets for representing temporal relations in mutual wills; Daedalus (Judge Asaro’s software assisting Italy’s examining magistrates with inquiries, and then when they turn prosecutors); a study in occurrences in court of allegations echoing the pretext archetype “The dog ate my homework” (even when the claim was not pretextuous); an application of Wigmore Charts to an analysis of both the argumentation and the rhetoric of an Italian arringa (final submissions to the court) from a real court case; editorial projects which promoted the emergence of evidence as a conspicuous field within AI & Law (thus overturning previous neglect); and a magnum opus (Nissan 2012a) which presents the state of the art of computational applications to legal evidence, police inquiries, or argumentation