An online learning approach to in-vivo tracking using synergistic features

In this paper we present an online algorithm for robustly tracking surgical tools in dynamic environments that can assist a surgeon during in-vivo robotic surgery procedures. The next generation of in-vivo robotic surgical devices includes integrated imaging and effector platforms that need to be controlled through real-time visual feedback. Our tracking algorithm learns the appearance of the tool online to account for appearance and perspective changes. In addition, the tracker uses multiple features working together to model the object and discover new areas of the tool as it moves quickly, exits and re-enters the scene, or becomes occluded and requires recovery. The algorithm can persist through changes in lighting and pose by using a memory database, which is built online, using a series of features working together to exploit different aspects of the object being tracked. We present results using real in-vivo imaging data from a human partial nephrectomy

A learning algorithm for visual pose estimation of continuum robots

Continuum robots offer significant advantages for surgical intervention due to their down-scalability, dexterity, and structural flexibility. While structural compliance offers a passive way to guard against trauma, it necessitates robust methods for online estimation of the robot configuration in order to enable precise position and manipulation control. In this paper, we address the pose estimation problem by applying a novel mapping of the robot configuration to a feature descriptor space using stereo vision. We generate a mapping of known features through a supervised learning algorithm that relates the feature descriptor to known ground truth. Features are represented in a reduced sub-space, which we call eigen-features. The descriptor provides some robustness to occlusions, which are inherent to surgical environments, and the methodology that we describe can be applied to multi-segment continuum robots for closed-loop control. Experimental validation on a single-segment continuum robot demonstrates the robustness and efficacy of the algorithm for configuration estimation. Results show that the errors are in the range of 1°

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

How does finasteride affect time-dependent modulatory effect of morphine-induced analgesia

Finasterid, testosteronu dihidrotestosterona dönüştüren 5&#945;-redüktaz enziminin inhibitörüdür. Bu çalışmanın amacı, finasteridin morfinin analjezik etkisini zaman bağımlı olarak nasıl etkilediğini araştırmaktır. Deneylerde 12 saat aydınlık/12 saat karanlık döngüsü ile senkronize edilmiş 25-40 gram ağırlığında albino erkek fareler ve 55 ± 0.5ºC&#8217;de sıcak plaka testi kullanılmıştır. Tüm gruplarda deneyler, ışıklar yandıktan sonra 1., 5., 9., 13.,17. ve 21. saatlerde yapılmıştır. Bazal ağrı duyarlılığı ve morfinin analjezik etkisi, onar farelik gruplarda sıcak plaka testinden 30 dakika önce s.c. 10 mg/kg serum fizyolojik ve 10 mg/kg morfin uygulanarak saptanmıştır. Sıcak plaka testinden 50 dakika önce s.c. 15 mg/kg finasterid uygulanarak tek başına analjezik etkisi olup olmadığı araştırılmıştır. Finasterid ve morfin etkileşimini incelemek için aynı saatlerde, sıcak plaka testinden 50 dakika önce 15 mg/kg finasterid ve 30 dakika önce 10 mg/kg morfin cilt altı uygulanmıştır. Deney sonuçlarının standardizasyonu açısından 3 saniyeden daha kısa süreli yanıtlar &#8220;spontan yanıt&#8221; olarak değerlendirilmiş ve hesaplamalara dahil edilmemişlerdir. Farelerde yanık hasarı oluşturmamak için maksimum yanıt süresi 45 saniye olarak kabul edilmiştir. Mevsim değişiklerinden etkilenmemek için tüm deneyler Haziran ve Temmuz aylarında yapılmıştır. Güniçinde 6 değişik zamanda elde edilen data ortalama ± standart hata şeklinde ifade edilmiştir. Elde edilen data gereken yerlerde student t-test, varyans analizi (ANOVA) veya Kruskal Wallis varyans analizi ile değerlendirilmiştir. Finasteridin morfin yanıtlarına etkisinin aktivite periyodunda istirahat periyoduna nazaran, özellikle ışıklar yandıktan sonra 13. ve 21. saatlerde, çok daha belirgin olduğu görülmüştür. Bulgularımız, finasteridin morfinin antinosiseptif etkisini potansiye ettiğini ve aynı zamanda bu potansiyasyonun güniçi zaman bağımlılığı gösterdiğini işaret etmektedir.Finasteride inhibits 5&#945;-reductase which converts testosterone to dihydrotestosterone. The aim of this study is to evaluate how finasteride affects the analgesic effect of morphine time-dependently. Local bred albino male mice (25-40 gram) synchronized with a standard light-dark regimen (12hours:12hours Light:Dark, lights on 08:00) were used. All experiment groups include 10-12 mice and were tested at six time points of the day as 1, 5, 9, 13, 17 and 21 hours after lights on. All drugs were administered subcutaneously. Basal pain sensitivity (saline; 10 mg/kg) and morphine-induced analgesia (10 mg/kg) were determined 30 minutes before hot-plate test (55 ± 0.5ºC). To test the administration time-dependent interaction, a third group of animals were injected with a predetermined dose of finasteride (15 mg/kg) 20 minutes before morphine and response latencies were tested. Response latencies shorter than 3 seconds were regarded as spontaneous and excluded. To avoid heat injury, animals not responding within 45 seconds were removed from the hot-plate. To avoid the seasonal variations all experiments were performed in June and July. Data analyzed by ANOVA or Kruskal Wallis and student t-test where necessary. The results of this study indicate that there is time-dependent interaction between finasteride and morphine-induced analgesia. In the dark period, especially 13 and 21 hours after lights on, finasteride enhanced morphine-induced analgesia

The Contract as Social Artifact

This article outlines a distinctive, albeit not entirely unprecedented, research agenda for the sociolegal study of contracts. In the past, law and society scholars have tended to examine contracts either through the intellectual history of contract doctrine ‘‘on the books’’ or through the empirical study of how real-world exchange relations are governed ‘‘in action.’’ Although both of these traditions have contributed greatly to our understanding of contract law, neither has devoted much attention to the most distinctive concrete product of contractual transactionsFcontract documents themselves. Without denying the value of studying either contract doctrine or relational governance, this article argues that contract documents are independently interesting social artifacts and that they should be studied as such. As social artifacts, contracts possess both technical and symbolic properties, and the sociolegal study of contract-as-artifact can profitably apply prevailing social scientific theories of technology and symbolism to understand both: (1) the microdynamics of why and how transacting parties craft individual contract devices, and (2) the macrodynamics of why and how larger social systems generate and sustain distinctive contract regimes. Seen in this light, the microdynamics of contract implicate ‘‘technical’’ theories of transaction cost engineering and private lawmaking, and ‘‘symbolic’’ theories of ceremony and gesture. In a parallel fashion, the macrodynamics of contract implicate ‘‘technical’’ theories of innovation diffusion, path dependence, and technology cycles, and ‘‘symbolic’’ theories of ideology, legitimacy, and communication. Together, these micro and macro explorations suggest that contract artifacts may best be understood as scripts and signalsFcollections of symbols designed to field technically efficacious practical action when interpreted by culture-bearing social actors within the context of preexisting vocabularies and conventions