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2. Self-assembled neuromorphic networks at self-organized criticality in Ag-hBN platform

Author

Rao, Ankit, Sanjay, Sooraj, Ahmadi, Majid, Venugopalrao, Anirudh, Bhat, Navakanta, Kooi, Bart, Raghavan, Srinivasan, and Nukala, Pavan

Subjects
Quantitative Biology - Neurons and Cognition, Condensed Matter - Disordered Systems and Neural Networks, Computer Science - Emerging Technologies
Abstract

Networks and systems which exhibit brain-like behavior can analyze information from intrinsically noisy and unstructured data with very low power consumption. Such characteristics arise due to the critical nature and complex interconnectivity of the brain and its neuronal network. We demonstrate that a system comprising of multilayer hexagonal Boron Nitride (hBN) films contacted with Silver (Ag), that can uniquely host two different self-assembled networks, which are self-organized at criticality (SOC). This system shows bipolar resistive switching between high resistance (HRS) and low resistance states (LRS). In the HRS, Ag clusters (nodes) intercalate in the van der Waals gaps of hBN forming a network of tunnel junctions, whereas the LRS contains a network of Ag filaments. The temporal avalanche dynamics in both these states exhibit power-law scaling, long-range temporal correlation, and SOC. These networks can be tuned from one to another with voltage as a control parameter. For the first time, different neuron-like networks are realized in a single CMOS compatible, 2D materials platform.

Published
2022

6. List of contributors

Author

Behera, Manaswini, primary, Bhadra, Sudipa, additional, Bhaduri, Soumyadeep, additional, Bhowmick, G.D., additional, Cardozo, Jussara Câmara, additional, Cavalcanti, Lívia N., additional, Chakraborty, Annesha, additional, Chhatbar, Monali, additional, Das, Bhaskar, additional, Das, Pranjal P., additional, Das, Sovik, additional, Das, Indrasis, additional, Deore, Dipak, additional, dos Santos, Elisama V., additional, Ghangrekar, M.M., additional, Ghosh, Rahul, additional, Ghosh, Dipankar, additional, Gole, Ankita, additional, Gondim, Amanda D., additional, Guha, Shreyasmita, additional, Ihjas, K., additional, Jadhav, Dipak Ashok, additional, Jayaraj, K.K., additional, Kailasa, Suresh Kumar, additional, Kaushik, Anubha, additional, Loor-Urgilés, Luis D., additional, Maddirala, Shivani, additional, Mal, Supriyo, additional, Malkapuram, Surya Teja, additional, Martínez-Huitle, Carlos A., additional, Mungray, Alka, additional, Mungray, Arvind Kumar, additional, Neethu, B., additional, Oliveira, Herbet L., additional, Pendse, Vedant Vijay, additional, Prasad, Shiv, additional, Pulipati, Tejovardhan, additional, Purkait, Mihir K., additional, Rao, Ankit, additional, Rathore, Dheeraj, additional, Roy, Dona, additional, Sai Teja, A., additional, Samanta, Ayan, additional, Santos, José Eudes L., additional, Sevda, Surajbhan, additional, Sharma, Mukesh, additional, Singh, Anoop, additional, Sinha, Juhi, additional, Sonawane, Shirish Hari, additional, Surti, Parini, additional, Thakur, Somil, additional, Venkatramanan, Veluswamy, additional, and Zekker, Ivar, additional

Published
2024
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8. A randomised phase 2 study of intermittent versus continuous dosing of dabrafenib plus trametinib in patients with BRAFV600 mutant advanced melanoma (INTERIM)

Author

Dayimu, Alimu, Gupta, Avinash, Matin, Rubeta N., Nobes, Jenny, Board, Ruth, Payne, Miranda, Rao, Ankit, Fusi, Alberto, Danson, Sarah, Eccles, Bryony, Carser, Judith, Brown, Ciara O’Hanlon, Steven, Neil, Bhattacharyya, Madhumita, Brown, Ewan, Gonzalez, Michael, Highley, Martin, Pickering, Lisa, Kumar, Satish, Waterston, Ashita, Burghel, George, Demain, Leigh, Baker, Eleanor, Wulff, Jerome, Qian, Wendi, Twelves, Sophie, Middleton, Mark, and Corrie, Pippa

Published
2024
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22. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial

Author

Llovet, Josep M, primary, Kudo, Masatoshi, additional, Merle, Philippe, additional, Meyer, Tim, additional, Qin, Shukui, additional, Ikeda, Masafumi, additional, Xu, Ruocai, additional, Edeline, Julien, additional, Ryoo, Baek-Yeol, additional, Ren, Zhenggang, additional, Masi, Gianluca, additional, Kwiatkowski, Mariusz, additional, Lim, Ho Yeong, additional, Kim, Jee Hyun, additional, Breder, Valeriy, additional, Kumada, Hiromitsu, additional, Cheng, Ann-Lii, additional, Galle, Peter R, additional, Kaneko, Shuichi, additional, Wang, Anran, additional, Mody, Kalgi, additional, Dutcus, Corina, additional, Dubrovsky, Leonid, additional, Siegel, Abby B, additional, Finn, Richard S, additional, Strasser, Simone, additional, Thompson, Alexander, additional, Roohullah, Aflah, additional, Sievert, William, additional, Andelkovic, Vladimir, additional, Knox, Jennifer, additional, Davies, Janine, additional, Asselah, Jamil, additional, Brahmania, Mayur, additional, Majeed, Habeeb, additional, Villanueva, Luis, additional, Yanez Weber, Patricio, additional, Garrido, Marcelo, additional, Pizarro, Gonzalo Ignacio, additional, Yanez, Nicolas, additional, Ou, Shuangyan, additional, Pan, Hongming, additional, Meng, Zhiqiang, additional, Gu, Kangsheng, additional, Chen, Xi, additional, Zhang, Tao, additional, Hao, Chunyi, additional, Cao, Peiguo, additional, Guo, Yabing, additional, Xiao, Juxiang, additional, Fang, Weijia, additional, Wang, Xin, additional, Bai, Yuxian, additional, Chen, Xiaoming, additional, Yan, Dong, additional, Zhao, Hong, additional, Ying, Jieer, additional, Bonilla, Carlos, additional, Urrego, Olga, additional, Zambrano, Angela, additional, Lema, Mauricio, additional, Restrepo Gutierrez, Juan Carlos, additional, Cardona, Andres, additional, Franco Millan, Sandra, additional, Oscar, Madiedo, additional, Ramos, Victor, additional, LeSourd, Samuel, additional, Bronowicki, Jean-Pierre, additional, Bourliere, Marc, additional, Cattan, Stephane, additional, Bouattour, Mohamed, additional, Mineur, Laurent, additional, Regnault, Helene, additional, Dauvois, Barbara, additional, Schulze, Kornelius, additional, Folprecht, Gunnar, additional, Geier, Andreas, additional, Waidmann, Oliver, additional, Finkelmeier, Fabian, additional, Venerito, Marino, additional, Berres, Marie-Luise, additional, Berg, Thomas, additional, Lange, Christian, additional, Schmidt, Hartmut, additional, Waldschmidt, Dirk T, additional, Bitzer, Michael, additional, McDermott, Ray, additional, Duffy, Austin, additional, Zagonel, Vittorina, additional, Tonini, Giuseppe, additional, Piscaglia, Fabio, additional, Gori, Stefania, additional, Rizzo, Mimma, additional, Biscaldi, Elisa, additional, Foltran, Luisa, additional, Cabibbo, Giuseppe, additional, Aikata, Hiroshi, additional, Numata, Kazushi, additional, Marusawa, Hiroyuki, additional, Kato, Naoya, additional, Kurosaki, Masayuki, additional, Morimoto, Manabu, additional, Yamashita, Tatsuya, additional, Koga, Hironori, additional, Masaki, Tsutomu, additional, Tateishi, Ryosuke, additional, Inaba, Yoshitaka, additional, Arakawa, Tomohiro, additional, Suzuki, Yoshiyuki, additional, Akua, Norio, additional, Kobayashi, Masahiro, additional, Hosaka, Tetsuya, additional, Nakamuta, Makoto, additional, Oza, Noriko, additional, Kondo, Shunsuke, additional, Furuse, Junji, additional, Nagashima, Fumio, additional, Kitano, Masayuki, additional, Takaguchi, Koichi, additional, Kim, Tae-You, additional, Kim, Han Sang, additional, Hernandez Hernandez, Carlos, additional, Motola Kuba, Daniel, additional, Segura Gonzalez, Manuel, additional, Cabrera Luviano, Jesus, additional, Huitzil Melendez, Fidel, additional, Ramirez Godinez, Francisco, additional, Silva-Bravo, Fernando, additional, Gane, Edward, additional, Stedman, Catherine, additional, Wyrwicz, Lucjan, additional, Nowakowska-Zajdel, Ewa, additional, Kraj, Leszek, additional, Janczewska, Ewa, additional, Surma-Wlodarczyk, Renata, additional, Sekacheva, Marina, additional, Orlova, Rashida, additional, Vasilyev, Alexander, additional, Zukov, Ruslan, additional, Vladimirov, Vladimir, additional, Minguez, Beatriz, additional, Matilla Pena, Ana, additional, Fernandez Castroagudin, Javier, additional, Romero Gomez, Manuel, additional, Luis Lledo, Jose, additional, Rubin, Angel, additional, Garcia Sanchez, Araceli, additional, Calleja Panero, Jose, additional, Yu, Ming-Chin, additional, Shen, Ying-Chun, additional, Huang, Yi-Hsiang, additional, Jeng, Long-Bin, additional, Chang, Ting-Tsung, additional, Yang, Sheng-Shun, additional, Chen, Shinn-Cherng, additional, Dechaphunkul, Arunee, additional, Tanwandee, Tawesak, additional, Leerapun, Apinya, additional, Seker, Mesut, additional, Harputluoglu, Hakan, additional, Cicin, Irfan, additional, Oksuzoglu, Berna, additional, Bilici, Mehmet, additional, Sezgin Goksu, Sema, additional, Artac, Mehmet, additional, Cil, Timucin, additional, Yalcin, Suayib, additional, Sarker, Debashis, additional, Rao, Ankit, additional, Palmer, Daniel, additional, Evans, Jeff, additional, Hubner, Richard, additional, Finn, Richard, additional, Ulahannan, Susanna, additional, Zakari, Ahmed, additional, Feun, Lynn, additional, Al-Rajabi, Raed, additional, Sung, Max, additional, He, Aiwu, additional, Kardosh, Adel, additional, Goyal, Lipika, additional, Li, Daneng, additional, Choi, Minsig, additional, Posada, Juan, additional, Dodlapati, Jyothi, additional, Shroff, Rachna, additional, Agrawal, Saurabh, additional, Gopaluni, Srivalli, additional, Akce, Mehmet, additional, Alese, Olatunji, additional, Baron, Ari, additional, Dunne, Richard, additional, Loaiza-Bonilla, Arturo, additional, and Frenette, Catherine, additional

Published
2023
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23. A randomised phase 2 study of intermittent versus continuous dosing of dabrafenib plus trametinib in patients with BRAFV600 mutant advanced melanoma (INTERIM)

Author

Dayimu, Alimu, primary, Gupta, Avinash, additional, Matin, Rubeta N, additional, Nobes, Jenny, additional, Board, Ruth, additional, Payne, Miranda, additional, Rao, Ankit, additional, Fusi, Alberto, additional, Danson, Sarah, additional, Eccles, Bryony, additional, Carser, Judith, additional, Brown, Ciara O’Hanlon, additional, Steven, Neil, additional, Bhattacharyya, Madhumita, additional, Brown, Ewan, additional, Gonzalez, Michael, additional, Highley, Martin, additional, Pickering, Lisa, additional, Kumar, Satish, additional, Waterston, Ashita, additional, Burghel, George, additional, Demain, Leigh, additional, Baker, Eleanor, additional, Wulff, Jerome, additional, Qian, Wendi, additional, Twelves, Sophie, additional, Middleton, Mark, additional, and Corrie, Pippa, additional

Published
2023
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24. Engineering an improved dendritic cell vaccine expressing whole antigen following non-viral transfection

Author

Rao, Ankit Rohit

Subjects
616.994, QR180 Immunology, QR355 Virology, RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Abstract

Dendritic cells are efficient antigen-presenting-cells that can be used in tumour-antigen specific vaccination for malignant disease. Melanoma patients were recently treated with a dendritic cell vaccine expressing gp100 and Melan-A antigens after non-viral (CL22 peptide) transfection. Although clinical and immunological responses were noted, there was no correlation between responses and whole antigen expression levels in the vaccine cells that varied widely. Here, it is established that patient cells expressed detectable levels of Class I restricted epitopes from both antigens, although there was no correlation with whole antigen detection. CL22 transfected dendritic cells could simultaneously present a viral antigen (EBNA1) to CD8 and CD4 T-cells, which had not previously been demonstrated. Using RNA transfection, it was demonstrated that early after transfection cells are whole Melan-A positive yet negative for Class I epitopes and with time Melan-A antigen levels fall whilst Class I epitopes are generated. Loss of whole antigen expression seemed related to lysosomal function and, unlike the viral antigen EBNA1, Class I presentation from Melan-A was lysosome-dependent. For Class II presentation of EBNA1, cellular localisation seems to determine access to the Class II pathway although this depends on the time-scale over which epitope presentation is assessed.

Published
2012

30. THE CHANGES OF ENDOTRACHEAL TUBE INTRACUFF PRESSURE DUE TO CHANGE IN HEAD AND NECK POSITION IN MRM SURGERY.

Author

Rao, Ankit, Ahmad, Shahbaz, Arya, Saurabh, Arya, Sunil Kumar, Deo, Narendra, Singh, Suresh, Sharma, Santosh Kumar, Kumar, Avinash, Barthwal, Abhilasha, and Gupta, Pradeep Kumar

Subjects
*ARTIFICIAL respiration, *ENDOTRACHEAL tubes, *NECK, *INHALATION anesthetics, *TRACHEAL stenosis, *BLOOD flow
Abstract

Introduction: The safety margin of tracheal tube cuff pressure lies between excessive and insufficient pressure. Specifically, insufficient pressure can lead to air leakage, which lessens the effect of mechanical ventilation and results in the leakage of inhalation anesthetics, while excessive pressure can cause serious injury and affect blood flow to the tracheal mucosa, resulting in cough, hoarseness of voice prolonged intubation may cause tracheal stenosis, fistula, or tracheal rupture. Movement of the head and neck and the resulting displacement of the tracheal tube can alter cuff pressure. Material and Methods: We collect this sample size by using purposive sampling method. We select the individual who full fill the inclusion criteria and also give consent for participating in study. Result: In this study 59 (59%) female and 41 (41%) males. This study shows that 20 to 30 ET Cuff Pressure after change in Head and Neck Position in 41 (41%) cases and above 30 ET Cuff Pressure after change in Head and Neck Position in 59 (59%). Conclusion: It has been observed that change in average ETT cuff pressure was in between 6 cm of H2O after every 15 minutes interval, and every time when the ETT cuff pressure was found to be more than 25 cm of H2O, we reduced to within normal limits (25 cm of H2O) with the help of digital manometer. On the basis of the present study we arrived to the following conclusion that repeated reducing of ETT cuff pressure to within normal range (25 cm of H2O) lead to lesser complication of sore throat and hoarseness of voice as compared to the previous studies done for the same. Hence we can conclude that, ETT cuff pressure measuring manometer - (AG Cuffill) is an important tool to regulate ETT cuff pressure during intraoperative period, and it also helps to reduce post-operative complications like sore throat and hoarseness of voice. [ABSTRACT FROM AUTHOR]

Published
2023

32. A comparative study of dexmedetomedine and clonidine as adjuvant to levobupivacaine for epidural anesthesia in lower abdominal and lower limb surgeries.

Author

Gupta, Pradeep Kumar, Deo, Narendra, Singh, Suresh, Arya, Sunil Kumar, Sharma, Santosh Kumar, Ahmad, Shahbaz, Bhusan, Anubhav, Yadav, Narendra Singh, Barthwal, Abhilasha, and Rao, Ankit

Subjects
EPIDURAL anesthesia, CLONIDINE, ADRENERGIC agonists, ANALGESIA, LOCAL anesthetics, COMPARATIVE studies, SPINAL infusions
Abstract

BACKGROUND AND AIMS: The duration and quality of analgesia is improved when a local anesthetic is combined with alpha 2 adrenergic agonist. Though, the effects of clonidine on local anesthetics have been extensively studied, there are limited studies demonstrating the effects of epidural dexmedetomidine on local anesthetics. The aim of the study is to compare the efficacy of dexmeditomedine and clonidine as adjuvant to levobupivacaine for epidural anesthesia in lower abdominal and lower limb surgeries. MATERIAL AND METHODS: This Prospective comparative study was done to assess the efficacy and clinical profile of two a2 adrenergic agonists - clonidine and dexmedetomidine administered epidurally in combination with intrathecal 0.5%levobupivacaine. 60 adult patients ASA Class I and II undergoing lower abdomen and lower limb surgery were randomly assigned into two groups, to receive either epidural dexmedetomidine (1.5μg/kg) or clonidine (2 μg/kg) with 0.5% isobaric levobupivacaine. RESULTS: Based on the VAS score of the patients and time taken for rescue analgesia, it was found that better post-operative analgesia was provided for longer duration by dexmedetomidine than clonidine. Though no significant differences have been observed based on the hemodynamic parameters between both the groups of the patients, dexmedetomidine has shown beteer hemodynamic stability as compared to clonidine. CONCLUSION: It can be concluded that in patients undergoing lower abdominal and lower limb surgeries, administration of epidural anaesthesia with 0.5% of Levobupivacaine with dexmedetomidine provided better and longer post-operative analgesia as compared to clonidine. [ABSTRACT FROM AUTHOR]

Published
2023

33. COMPARISON OF THE ANALGESIC EFFICACY OF ULTRASOUND-GUIDED BILATERAL QUADRATUS LUMBORUM BLOCK VERSUS ERECTOR SPINAE PLAIN BLOCK FOR POSTOPERATIVE ANALGESIA IN TOTAL ABDOMINAL HYSTERECTOMY UNDER SPINAL ANAESTHESIA: A COMPARATIVE PROSPECTIVE STUDY.

Author

Barthwal, Abhilasha, Sharma, Santosh Kumar, Deo, Narendra, Arya, Sunil Kumar, Ahmad, Shahbaz, Singh, Suresh, Rai, Prashant Kumar, Pandey, Akansha, Gupta, Pradeep Kumar, and Rao, Ankit

Subjects
HYSTERO-oophorectomy, ERECTOR spinae muscles, VAGINAL hysterectomy, ANALGESIA, PATIENT satisfaction, SURGICAL site, LONGITUDINAL method
Abstract

Background: Hysterectomy is one of the most common major surgeries performed in gynaecology. post operative pain is an inevitable consequence of surgical incision involving full thickness of abdominal wall given in abdominal hysterectomy. Conventional method of pain management includes use of intravenous and oral NSAIDS and opioid. Use of Intrathecal opioid and epidural analgesia has been explored for post operative management. Regional anaesthesia gives a new ray of hope for post operative pain management. The aim of our study to compare the efficacy of bilateral Quadratus Lumborum block (QLB) and erector spinae plane block (ESPB) for post operative analgesia in total abdominal hysterectomy. Material and Method: This Prospective observational study was carried out among 60 patients, which scheduled for elective surgery after getting approval from ethical committee and informed written consent from all patients, the prospective observational study was conducted on adult patients of either sex satisfying inclusion criteria. In our study patients were randomized into 2 groups (30 patient in each group), group QLB (spinal anaesthesia + USG guided bilateral QL3 block) and group ESPB (spinal anaesthesia + USG guided bilateral ESPB block). Post operative pain using NRS, time for first rescue analgesia and total analgesic requirement of the patient amongst all two groups were observed and compared. Result: The mean NRS on rest and movement both were found to be significantly less in QLB group than ESPB group. Injection fentanyl was used as rescue analgesia for patients with NRS > 4. Patients belonging to group ESPB received rescue analgesia faster and significantly higher amount as compared with group QLB. Conclusion: It can be concluded that patient undergoing total abdominal hysterectomy surgery Quadratus lumborum block and erector spinae plane block, both are effective but Quadratus lumborum block is more effective in decreasing postoperative pain and post operative analgesic consumption and lead to greater patient satisfaction, without any serious side effect oral hemodynamic instability. [ABSTRACT FROM AUTHOR]

Published
2023

34. Self-assembled neuromorphic networks at self-organized criticality in Ag-hBN platform

Author

Rao, Ankit, Sanjay, Sooraj, Ahmadi, Majid, Venugopalrao, Anirudh, Bhat, Navakanta, Kooi, Bart, Raghavan, Srinivasan, and Nukala, Pavan

Subjects
FOS: Computer and information sciences, Emerging Technologies (cs.ET), Quantitative Biology - Neurons and Cognition, FOS: Biological sciences, Computer Science - Emerging Technologies, FOS: Physical sciences, Neurons and Cognition (q-bio.NC), Disordered Systems and Neural Networks (cond-mat.dis-nn), Condensed Matter - Disordered Systems and Neural Networks
Abstract

Networks and systems which exhibit brain-like behavior can analyze information from intrinsically noisy and unstructured data with very low power consumption. Such characteristics arise due to the critical nature and complex interconnectivity of the brain and its neuronal network. We demonstrate that a system comprising of multilayer hexagonal Boron Nitride (hBN) films contacted with Silver (Ag), that can uniquely host two different self-assembled networks, which are self-organized at criticality (SOC). This system shows bipolar resistive switching between high resistance (HRS) and low resistance states (LRS). In the HRS, Ag clusters (nodes) intercalate in the van der Waals gaps of hBN forming a network of tunnel junctions, whereas the LRS contains a network of Ag filaments. The temporal avalanche dynamics in both these states exhibit power-law scaling, long-range temporal correlation, and SOC. These networks can be tuned from one to another with voltage as a control parameter. For the first time, different neuron-like networks are realized in a single CMOS compatible, 2D materials platform.

Published
2023
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41. A randomised phase II clinical trial of low-dose cyclophosphamide and transarterial chemoembolization (TACE) with or without vaccination with dendritic cells (DC) pulsed with HepG2 lysate ex vivo in patients with hepatocellular carcinoma (HCC): The ImmunoTACE trial.

Author

Ma, Yuk Ting, primary, Kirkham, Amanda, additional, Curbishley, Stuart, additional, Rowe, Anna, additional, Blahova, Miroslava, additional, Mehrzad, Homoyon, additional, Karkhanis, Salil, additional, Punia, Pankaj, additional, James, Martin, additional, Rao, Ankit Rohit, additional, Stern, Nick, additional, Palmer, Daniel H., additional, Hull, Diana, additional, Lowe, Faye, additional, Douglas-Pugh, Jessica, additional, Bathurst, Camilla, additional, Wilkhu, Manpreet, additional, Yap, Christina, additional, and Adams, David H, additional

Published
2022
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42. Tu1291: MASS CYTOMETRY IDENTIFIES A DISCRETE POPULATION OF EFFECTOR MEMORY CD8 T CELLS AS A HALLMARK OF LIVER INJURY DUE TO IMMUNE CHECKPOINT INHIBITORS

Author

Astbury, Stuart, primary, Atallah, Edmond, additional, Bozward, Amber, additional, Krajewska, Natalia, additional, Wootton, Grace, additional, Grove, Jane I., additional, Franks, Hester, additional, Rao, Ankit, additional, Patel, Poulam, additional, Oo, Ye, additional, and Aithal, Guruprasad P., additional

Published
2022
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43. Finite element modelling and dynamic characteristic analysis of the human CTL-Spine

Author

Dayanand Shreyas, Rao Ankit, Kumar B.R. Dhruva, B. Khot Mantesh, Harshavardhan Shetty, and Chandrashekara C

Subjects
musculoskeletal diseases, education.field_of_study, Computer science, business.industry, Materials Science (miscellaneous), Modal analysis, Population, Biomechanics, Structural engineering, Industrial and Manufacturing Engineering, Finite element method, Vertebra, Vibration, CTL, medicine.anatomical_structure, Lumbar, medicine, Business and International Management, education, business
Abstract

Persistent exposure to whole body vibrations is the fundamental cause for lower back pain and disc degeneration. With an increasing amount of population exposed to whole body vibrations, a significant number of people experience fatal spine diseases. Substantial research is carried out to reduce the risk of spinal injuries. The dynamic characteristics of the cervical, thoracic and lumbar (CTL) region are studied extensively as individual sections of the spine. Few studies have focused on the CTL spine as an assembly of the three segments. In the present work, an authentic three dimensional geometrical model of the cervical, thoracic and lumbar spine is developed in mimics considering its natural curvature and the intervertebral discs are modeled in Design modeler. The natural frequency and mode shapes of the CTL spine are extracted using free vibration modal analysis considering 4.5 kg point mass on C1 vertebra and distributed mass of 40 kg on the CTL spine in Ansys Workbench. Six natural frequencies and their corresponding vibration modes are obtained from the finite element model. The results of this study aims to provide a reliable model for further biomechanical analysis and ergonomics.

Published
2020
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49. A randomised phase II clinical trial of low-dose cyclophosphamide and transarterial chemoembolization (TACE) with or without vaccination with dendritic cells (DC) pulsed with HepG2 lysate ex vivo in patients with hepatocellular carcinoma (HCC): The ImmunoTACE trial

Author

Ting Ma, Yuk, Kirkham, Amanda, Curbishley, Stuart, Rowe, Anna, Blahova, Miroslava, Mehrzad, Homoyon, Karkhanis, Salil, Punia, Pankaj, James, Martin, Rohit Rao, Ankit, Stern, Nick, Palmer, Daniel H., Hull, Diana, Lowe, Faye, Douglas-Pugh, Jessica, Bathurst, Camilla, Wilkhu, Manpreet, Christina Yap, and Adams, David H.

Subjects
Cancer Research, Oncology
Abstract

4012 Background: A previous study by our group using autologous monocyte-derived DC pulsed ex vivo with HepG2 cell lysate showed some clinical benefit with evidence of antigen-specific T-cell responses in patients with advanced HCC. The current trial reports the activity of this vaccine in combination with TACE in patients with HCC. All patients also received low-dose cyclophosphamide to deplete regulatory T cells and thereby enhance vaccination. Methods: Patients with intermediate stage HCC (performance status 0-2, Child Pugh A/B7) were randomised 1:1 to TACE plus low-dose cyclophosphamide (Group 1) or TACE plus low-dose cyclophosphamide plus dendritic cell vaccination (Group 2). Cyclophosphamide was administered on Day 1 and 29 followed by TACE on Day 31 (+/- DC infusion), with further cyclophosphamide on Days 60, 90 and 120 (+/- additional DC infusions on Days 62, 92 and 122). The primary endpoint was progression free survival (PFS) by RECIST v1.1. Secondary endpoints included radiological response by RECIST v1.1, PFS and radiological response according to modified (m) RECIST, overall survival (OS), immune response and toxicity. Target recruitment was 48 evaluable patients (24 patients in each arm) to detect a 20% increase in PFS rate at 1 year (30% vs 50%) with a relaxed one-sided statistical significance level of 20% and 80% power using a logrank test. Results: Between March 2016 and October 2019, 55 patients from 3 UK centres were randomised of whom 48 were evaluable (24 each arm). Median PFS by RECIST criteria was significantly longer in Group 2 compared to Group 1 (18.6 vs 10.4 months: hazard ratio (HR) 0.43, 80% CI -∞-0.59; one-sided p = 0.02). Median PFS using mRECIST criteria showed a similar magnitude of benefit (18.6 vs 10.8 months: HR 0.48, 95% CI 0.22-1.02). Median OS was 25.7 months in Group 2 vs 21.5 months in Group 1 (HR 0.61, 95% CI 0.27-1.38). Group 2 showed a higher overall response rate (complete and partial response) by RECIST (54% vs 29%) and mRECIST (75% vs 54%) and a higher disease control rate (complete and partial response and stable disease) by RECIST (92% vs 67%) and mRECIST (88% vs 67%). Treatment with DC infusions was well tolerated; the most common adverse events were chills (30%), fatigue (22%) and nausea (22%), all of which were low grade. Immune response analyses are currently ongoing. Conclusions: The addition of tumour lysate pulsed DC infusions to treatment with TACE plus low-dose cyclophosphamide significantly increased PFS in patients with HCC. To the best of our knowledge, this is the first randomised study to demonstrate efficacy using DC in HCC. Further investigation of the role of DC infusions in the treatment of HCC are warranted but will need to take into account the current evolving immunotherapy landscape. Clinical trial information: 11889464.

Published
2022
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