Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy

Design of a polishing tool for collaborative robotics using minimum viable product approach

This is an Author's Accepted Manuscript of an article published in Carlos Perez-Vidal, Luis Gracia, Samuel Sanchez-Caballero, J. Ernesto Solanes, Alessandro Saccon & Josep Tornero (2019) Design of a polishing tool for collaborative robotics using minimum viable product approach, International Journal of Computer Integrated Manufacturing, 32:9, 848-857, DOI: 10.1080/0951192X.2019.1637026 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/0951192X.2019.1637026[EN] A collaborative tool for robotic polishing is developed in this work in order to allow the simultaneous operation of the robot system and human operator to cooperatively carry out the polishing task. For this purpose, the collaborative environment is detailed and the polishing application is designed. Moreover, the polishing tool is developed and its implementation using the minimum viable product approach is obtained. Furthermore, a robust hybrid position-force control is proposed to use the developed tool attached to a robot system and some experiments are given to show its performance.This work was supported in part by the Ministerio de Ciencia e Innovacion (Spanish Government) under project [DPI2017-87656-C2-1-R] and the Generalitat Valenciana under Grant [VALi+ d APOSTD/2016/044].Perez-Vidal, C.; Gracia Calandin, LI.; Sanchez-Caballero, S.; Solanes Galbis, JE.; Saccon, A.; Tornero Montserrat, J. (2019). Design of a polishing tool for collaborative robotics using minimum viable product approach. International Journal of Computer Integrated Manufacturing. 32(9):848-857. https://doi.org/10.1080/0951192X.2019.1637026S848857329Alders, K., M. Lehe, and G. Wan. 2001. “Method for the Automatic Recognition of Surface Defects in Body Shells and Device for Carrying Out Said Method” US Patent 6,320,654, Accessed 2001 November. https://www.google.ch/patents/US6320654Alexopoulos, K., Mavrikios, D., & Chryssolouris, G. (2013). ErgoToolkit: an ergonomic analysis tool in a virtual manufacturing environment. International Journal of Computer Integrated Manufacturing, 26(5), 440-452. doi:10.1080/0951192x.2012.731610Andres, J., Gracia, L., & Tornero, J. (2011). Calibration and control of a redundant robotic workcell for milling tasks. International Journal of Computer Integrated Manufacturing, 24(6), 561-573. doi:10.1080/0951192x.2011.566284Arnal, L., Solanes, J. E., Molina, J., & Tornero, J. (2017). Detecting dings and dents on specular car body surfaces based on optical flow. Journal of Manufacturing Systems, 45, 306-321. doi:10.1016/j.jmsy.2017.07.006Blank, S. 2010. “Perfection By Subtraction - The Minimum Feature Set”. Accessed 2018 August. http://steveblank.com/2010/03/04/perfection-by-subtraction-the-minimum-feature-set/Dimeas, F., & Aspragathos, N. (2016). Online Stability in Human-Robot Cooperation with Admittance Control. IEEE Transactions on Haptics, 9(2), 267-278. doi:10.1109/toh.2016.2518670Fitzgerald, C. “Developing Baxter, A new industrial robot with common sense for U.S. manufacturing.” 2013.Gracia, L., Sala, A., & Garelli, F. (2012). A supervisory loop approach to fulfill workspace constraints in redundant robots. Robotics and Autonomous Systems, 60(1), 1-15. doi:10.1016/j.robot.2011.07.008Gracia, L., Sala, A., & Garelli, F. (2014). Robot coordination using task-priority and sliding-mode techniques. Robotics and Computer-Integrated Manufacturing, 30(1), 74-89. doi:10.1016/j.rcim.2013.08.003Gracia, L., Solanes, J. E., Muñoz-Benavent, P., Valls Miro, J., Perez-Vidal, C., & Tornero, J. (2018). Adaptive Sliding Mode Control for Robotic Surface Treatment Using Force Feedback. Mechatronics, 52, 102-118. doi:10.1016/j.mechatronics.2018.04.008Julius, R., Schürenberg, M., Schumacher, F., & Fay, A. (2017). Transformation of GRAFCET to PLC code including hierarchical structures. Control Engineering Practice, 64, 173-194. doi:10.1016/j.conengprac.2017.03.012. E. K. (2016). TOWARDS AN AUTOMATED POLISHING SYSTEM - CAPTURING MANUAL POLISHING OPERATIONS. International Journal of Research in Engineering and Technology, 05(07), 182-192. doi:10.15623/ijret.2016.0507030Khan, A. M., Yun, D., Zuhaib, K. M., Iqbal, J., Yan, R.-J., Khan, F., & Han, C. (2017). Estimation of Desired Motion Intention and compliance control for upper limb assist exoskeleton. International Journal of Control, Automation and Systems, 15(2), 802-814. doi:10.1007/s12555-015-0151-7Kirschner, D., Velik, R., Yahyanejad, S., Brandstötter, M., & Hofbaur, M. (2016). YuMi, Come and Play with Me! A Collaborative Robot for Piecing Together a Tangram Puzzle. Interactive Collaborative Robotics, 243-251. doi:10.1007/978-3-319-43955-6_29Mohammad, A. E. K., Hong, J., & Wang, D. (2018). Design of a force-controlled end-effector with low-inertia effect for robotic polishing using macro-mini robot approach. Robotics and Computer-Integrated Manufacturing, 49, 54-65. doi:10.1016/j.rcim.2017.05.011Nagata, F., Hase, T., Haga, Z., Omoto, M., & Watanabe, K. (2007). CAD/CAM-based position/force controller for a mold polishing robot. Mechatronics, 17(4-5), 207-216. doi:10.1016/j.mechatronics.2007.01.003Nakamura, Y., Hanafusa, H., & Yoshikawa, T. (1987). Task-Priority Based Redundancy Control of Robot Manipulators. The International Journal of Robotics Research, 6(2), 3-15. doi:10.1177/027836498700600201Ries, E. 2009. “What is the Minimum Viable Product”. March. Accessed 2018 August. http://venturehacks.com/articles/minimum-viable-productRobinson, F. 2001 “A Proven Methodology to Maximize Return on Risk”. Accessed 2018 August. http://www.syncdev.com/minimum-viable-productShepherd, S., & Buchstab, A. (2014). KUKA Robots On-Site. Robotic Fabrication in Architecture, Art and Design 2014, 373-380. doi:10.1007/978-3-319-04663-1_26SYMPLEXITY. “Symbiotic Human-Robot Solutions for Complex Surface Finishing Operations.” European project funded by E.U. through the H2020. Project no. 637080. Call: H2020-FoF-2014. Topic: FoF-06-2014. Starting date: 01/ 01/2015.Duration: 48 months. Accessed 2019 March. https://www.symplexity.eu/Vihlborg, P., I. Bryngelsson, B. Lindgren, L. G. Gunnarsson, and P. Graff. 2017. “Associatio between vibration exposure and hand-arm vibration symptoms in a Swedish mechanical industry.” February 2017.Vogel, J., Haddadin, S., Jarosiewicz, B., Simeral, J. D., Bacher, D., Hochberg, L. R., … van der Smagt, P. (2015). An assistive decision-and-control architecture for force-sensitive hand–arm systems driven by human–machine interfaces. 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P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Blunted Medial Prefrontal Cortico-Limbic Reward-Related Effective Connectivity and Depression

Stratifying Resilience and Depression Longitudinally (STRADL) was supported by the Wellcome Trust through a Strategic Award (Grant No. 104036/Z/14/Z). Parts of the work were supported by a China Scholarship Council (Grant No. 201506040037 to SX), National Institutes of Health (Grant No. DA027764 to MRD), Lister Institute Prize Fellowship 2016–2021 (to DJS), Dr Mortimer and Theresa Sackler Foundation (AMM, HCW, and SML), Centre for Cognitive Ageing and Cognitive Epidemiology (IJD and AMM), Medical Research Council and Biotechnology and Biological Sciences Research Council (Grant No. MR/K026992/1), Royal College of Physicians of Edinburgh John, Margaret, Alfred and Stewart Sim fellowship (to HCW), and University of Edinburgh, Edinburgh Scientific Academic TmPCk College Fellowship (to HCW). The Chief Scientist Office of the Scottish Government Health Department (Grant No. CZD/16/6) and Scottish Funding Council (Grant No. HR03006) provided core support for Generation Scotland. Data acquisition was additionally supported by the Scottish Mental Health Research Network and Scottish Government’s Support for Science initiative. LR, HCW, and AMM, received financial support from Pfizer (formerly Wyeth) in relation to imaging studies of people with schizophrenia and bipolar disorder. AMM has previously received grant support from Lilly and Janssen. SML has received honoraria for lectures, chairing meetings, and consultancy work from Janssen in connection with brain imaging and therapeutic initiatives for psychosis. JDS has received funding via an honorarium associated with a lecture or Wyeth and funding from Indivior for a study on opioid dependency. No other disclosures were reported. The authors declare no conflict of interest.Peer reviewedPublisher PD

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Final report on LDRD project : single-photon-sensitive imaging detector arrays at 1600 nm.

The key need that this project has addressed is a short-wave infrared light detector for ranging (LIDAR) imaging at temperatures greater than 100K, as desired by nonproliferation and work for other customers. Several novel device structures to improve avalanche photodiodes (APDs) were fabricated to achieve the desired APD performance. A primary challenge to achieving high sensitivity APDs at 1550 nm is that the small band-gap materials (e.g., InGaAs or Ge) necessary to detect low-energy photons exhibit higher dark counts and higher multiplication noise compared to materials like silicon. To overcome these historical problems APDs were designed and fabricated using separate absorption and multiplication (SAM) regions. The absorption regions used (InGaAs or Ge) to leverage these materials 1550 nm sensitivity. Geiger mode detection was chosen to circumvent gain noise issues in the III-V and Ge multiplication regions, while a novel Ge/Si device was built to examine the utility of transferring photoelectrons in a silicon multiplication region. Silicon is known to have very good analog and GM multiplication properties. The proposed devices represented a high-risk for high-reward approach. Therefore one primary goal of this work was to experimentally resolve uncertainty about the novel APD structures. This work specifically examined three different designs. An InGaAs/InAlAs Geiger mode (GM) structure was proposed for the superior multiplication properties of the InAlAs. The hypothesis to be tested in this structure was whether InAlAs really presented an advantage in GM. A Ge/Si SAM was proposed representing the best possible multiplication material (i.e., silicon), however, significant uncertainty existed about both the Ge material quality and the ability to transfer photoelectrons across the Ge/Si interface. Finally a third pure germanium GM structure was proposed because bulk germanium has been reported to have better dark count properties. However, significant uncertainty existed about the quantum efficiency at 1550 nm the necessary operating temperature. This project has resulted in several conclusions after fabrication and measurement of the proposed structures. We have successfully demonstrated the Ge/Si proof-of-concept in producing high analog gain in a silicon region while absorbing in a Ge region. This has included significant Ge processing infrastructure development at Sandia. However, sensitivity is limited at low temperatures due to high dark currents that we ascribe to tunneling. This leaves remaining uncertainty about whether this structure can achieve the desired performance with further development. GM detection in InGaAs/InAlAs, Ge/Si, Si and pure Ge devices fabricated at Sandia was shown to overcome gain noise challenges, which represents critical learning that will enable Sandia to respond to future single photon detection needs. However, challenges to the operation of these devices in GM remain. The InAlAs multiplication region was not found to be significantly superior to current InP regions for GM, however, improved multiplication region design of InGaAs/InP APDs has been highlighted. For Ge GM detectors it still remains unclear whether an optimal trade-off of parameters can achieve the necessary sensitivity at 1550 nm. To further examine these remaining questions, as well as other application spaces for these technologies, funding for an Intelligence Community post-doc was awarded this year

MultiCellDS: a standard and a community for sharing multicellular data

Cell biology is increasingly focused on cellular heterogeneity and multicellular systems. To make the fullest use of experimental, clinical, and computational efforts, we need standardized data formats, community-curated "public data libraries", and tools to combine and analyze shared data. To address these needs, our multidisciplinary community created MultiCellDS (MultiCellular Data Standard): an extensible standard, a library of digital cell lines and tissue snapshots, and support software. With the help of experimentalists, clinicians, modelers, and data and library scientists, we can grow this seed into a community-owned ecosystem of shared data and tools, to the benefit of basic science, engineering, and human health

Final report on LDRD project 52722 : radiation hardened optoelectronic components for space-based applications.

This report describes the research accomplishments achieved under the LDRD Project 'Radiation Hardened Optoelectronic Components for Space-Based Applications.' The aim of this LDRD has been to investigate the radiation hardness of vertical-cavity surface-emitting lasers (VCSELs) and photodiodes by looking at both the effects of total dose and of single-event upsets on the electrical and optical characteristics of VCSELs and photodiodes. These investigations were intended to provide guidance for the eventual integration of radiation hardened VCSELs and photodiodes with rad-hard driver and receiver electronics from an external vendor for space applications. During this one-year project, we have fabricated GaAs-based VCSELs and photodiodes, investigated ionization-induced transient effects due to high-energy protons, and measured the degradation of performance from both high-energy protons and neutrons