Autofluorescence lifetime augmented reality as a means for real-time robotic surgery guidance in human patients.

Due to loss of tactile feedback the assessment of tumor margins during robotic surgery is based only on visual inspection, which is neither significantly sensitive nor specific. Here we demonstrate time-resolved fluorescence spectroscopy (TRFS) as a novel technique to complement the visual inspection of oral cancers during transoral robotic surgery (TORS) in real-time and without the need for exogenous contrast agents. TRFS enables identification of cancerous tissue by its distinct autofluorescence signature that is associated with the alteration of tissue structure and biochemical profile. A prototype TRFS instrument was integrated synergistically with the da Vinci Surgical robot and the combined system was validated in swine and human patients. Label-free and real-time assessment and visualization of tissue biochemical features during robotic surgery procedure, as demonstrated here, not only has the potential to improve the intraoperative decision making during TORS but also other robotic procedures without modification of conventional clinical protocols

Определение координат пользователя в спутниковых навигационных системах

Запропоновано систему лінійних алгебраїчних рівнянь за допомогою якої можна визначати координати користувача та поправку різниці часів годинників супутника та користувача в супутникових навігаційних системах.In satellite navigation systems (SNS) the user’s and satellites’ coordinates and the difference between the satellite and the user clocks are connected by the system of nonlinear equations of pseudo-distances between satellites and the user. The usage of these equations in calculations is not convenient. Therefore, for calculation of the user’s coordinates and the difference between clocks in SNS the linearized by Taylor series expansion and rejection of members of the second order of smallness equations are used. Thus the calculation of these variables is carried out by iterations. By algebraic manipulations it is possible to transform the system of nonlinear equations of pseudo-distances between satellites and the user into a system of linear equations about the coordinates of the user and the difference between the satellites’ and the user’s clocks. Application of the method of iteration is not required. Therefore, the application of such a system of linear equations will reduce the number and the count of these variables.Предложена система линейных алгебраических уравнений с помощью которой можна определять координаты пользователя и поправку разности времен часов спутника и пользователя в спутниковых навигационных системах

Neurology

Contains research objectives and reports on five research projects.U.S. Public Health Service (MH-06175-02)U.S. Navy (Office of Naval Research (Nonr-1841(70))U. S. Air Force (AF 49(638)-1313)U.S. Public Health Service (B-3055-4)U.S. Public Health Service (B-3090-4

Neurology

Contains reports on six research projects.U. S. Public Health Service (B-3055-4, B-3090-4, MH-06175-02)U. S. Air Force (AF49(638)-1313)U.S. Navy. Office of Naval Research (Nonr-1841(70)

Soft balancing in the Americas : Latin American opposition to U.S. intervention, 1898–1936

In the aftermath of the 2003 U.S.-led invasion of Iraq, scholars of international relations debated how to best characterize the rising tide of global opposition. The concept of “soft balancing” emerged as an influential, though contested, explanation of a new phenomenon in a unipolar world: states seeking to constrain the ability of the United States to deploy military force by using multinational organizations, international law, and coalition building. Soft balancing can also be observed in regional unipolar systems. Multinational archival research reveals how Argentina, Mexico, and other Latin American countries responded to expanding U.S. power and military assertiveness in the early twentieth century through coordinated diplomatic maneuvering that provides a strong example of soft balancing. Examination of this earlier case makes an empirical contribution to the emerging soft-balancing literature and suggests that soft balancing need not lead to hard balancing or open conflict

Neurology

Contains reports on eight research projects.U.S. Navy (Office of Naval Research (Nonr-1841(70))U. S. Public Health Service (MH-06175-02)U. S. Air Force (AF49(638)-1313)U. S. Public Health Service (B-3055-4)U. S. Public Health Service (B-3090-4

Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies

Abstract Background Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2. Methods ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines. Results EGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50—80% cytotoxicity against four primary glioblastoma lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133– and CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets. Conclusion High-grade gliomas are suitable for specific targeting by armed ATC. These data, together with additional animal studies, may provide the preclinical support for the use of armed ATC as a valuable addition to current treatment regimens

Sex differences in renal mitochondrial function: A hormone-gous opportunity for research

Sex differences (biological distinctions between males and females) present a complex interplay of genetic, developmental, biological, and environmental factors. More and more studies are shedding light on the importance of sex differences in normal physiology and susceptibility to cancer, cardiovascular and renal conditions, and neurodegenerative diseases. This mini-review is devoted to the role of sex dimorphisms in renal function, with a focus on the distinctions between male and female mitochondria. Here, we cover the aspects of renal mitochondrial bioenergetics where sex differences have been reported to date, for instance, biogenesis, reactive oxygen species production, and oxidative stress. Special attention is devoted to the effects of sex hormones, such as estrogen and testosterone, on mitochondrial bioenergetics in the kidney in physiology and pathophysiology

MATILDA: Inclusive Data Science Pipelines Design through Computational Creativity

We argue for the need for a new generation of data science solutions that can democratize recent advances in data engineering and artificial intelligence for non-technical users from various disciplines, enabling them to unlock the full potential of these solutions. To do so, we adopt an approach whereby computational creativity and conversational computing are combined to guide non-specialists intuitively to explore and extract knowledge from data collections. The paper introduces MATILDA, a creativity-based data science design platform, showing how it can support the design process of data science pipelines guided by human and computational creativity

Oncolytic DNX-2401 Virotherapy Plus Pembrolizumab in Recurrent Glioblastoma: A Phase 1/2 Trial

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2-20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1-69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7-13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05-0.87). A total of 56.2% (95% CI 41.1-70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients