Clinical Decision Support for Integrated Cyber-Physical Systems: A Mixed Methods Approach

We describe the design and implementation of a clinical decision support system for assessing risk of cerebral vasospasm in patients who have been treated for aneurysmal subarachnoid hemorrhage. We illustrate the need for such clinical decision support systems in the intensive care environment, and propose a three pronged approach to constructing them, which we believe presents a balanced approach to patient modeling. We illustrate the data collection process, choice and development of models, system architecture, and methodology for user interface design. We close with a description of future work, a proposed evaluation mechanism, and a description of the demo to be presented

GSA: A Framework for Rapid Prototyping of Smart Alarm Systems

We describe the Generic Smart Alarm, an architectural framework for the development of decision support modules for a variety of clinical applications. The need to quickly process patient vital signs and detect patient health events arises in many clinical scenarios, from clinical decision support to tele-health systems to home-care applications. The events detected during monitoring can be used as caregiver alarms, as triggers for further downstream processing or logging, or as discrete inputs to decision support systems or physiological closed-loop applications. We believe that all of these scenarios are similar, and share a common framework of design. In attempting to solve a particular instance of the problem, that of device alarm fatigue due to numerous false alarms, we devised a modular system based around this framework. This modular design allows us to easily customize the framework to address the specific needs of the various applications, and at the same time enables us to perform checking of consistency of the system. In the paper we discuss potential specific clinical applications of a generic smart alarm framework, present the proposed architecture of such a framework, and motivate the benefits of a generic framework for the development of new smart alarm or clinical decision support systems

CD160-Associated CD8 T-Cell Functional Impairment Is Independent of PD-1 Expression.

Expression of co-inhibitory molecules is generally associated with T-cell dysfunction in chronic viral infections such as HIV or HCV. However, their relative contribution in the T-cell impairment remains unclear. In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160+ CD8 T cells may be independent of PD-1 expression. The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160+ CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression

Divvy: An ATP Meta-system Based on Axiom Relevance Ordering

This paper describes two syntactic relevance orderings on the axioms available for proving a given conjecture, and an ATP meta-system that uses the orderings to select axioms to use in proof attempts. The system has been evaluated, and the results show that it is effective

Simian Immunodeficiency Virus Susceptibility, Immunology, and Microbiome in the Female Genital Tract of Adolescent Versus Adult Pigtail Macaques

In Sub-Saharan Africa, young women 15–24 years of age account for nearly 30% of all new HIV infections, however, biological and epidemiological factors underlying this disproportionate infection rate are unclear. In this study, we assessed biological contributors of SIV/HIV susceptibility in the female genital tract (FGT) using adolescent (n = 9) and adult (n = 10) pigtail macaques (PTMs) with weekly low-dose intravaginal challenges of SIV. Immunological variables were captured in vaginal tissue of PTMs by flow cytometry and cytokine assays. Vaginal biopsies were profiled by proteomic analysis. The vaginal microbiome was assessed by 16S rRNA sequencing. We were powered to detect a 2.2-fold increase in infection rates between age groups, however, we identified no significant differences in susceptibility. This model cannot capture epidemiological factors or may not best represent biological differences of HIV susceptibility. No immune cell subsets measured were significantly different between groups. Inflammatory marker MCP-1 was significantly higher (adj p = .02), and sCD40L trended higher (adj p = .06) in vaginal cytobrushes of adults. Proteomic analysis of vaginal biopsies showed no significant (adj p < .05) protein or pathway differences between groups. Vaginal microbiomes were not significantly different between groups. No differences were observed between age groups in this PTM model, however, these animals may not reflect biological factors contributing to HIV risk such as those found in their human counterparts. This model is therefore not appropriate to explore human adolescent differences in HIV risk. Young women remain a key population at risk for HIV infection, and there is still a need for comprehensive assessment and intervention strategies for epidemic control of this uniquely vulnerable population

Prevention of tuberculosis in macaques after intravenous BCG immunization

Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide1. The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission1,2. Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta). Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb. Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography–computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis