Uncertainty in runtime verification : a survey

Runtime Verification can be defined as a collection of formal methods for studying the dynamic evaluation of execution traces against formal specifications. Aside from creating a monitor from specifications and building algorithms for the evaluation of the trace, the process of gathering events and making them available for the monitor and the communication between the system under analysis and the monitor are critical and important steps in the runtime verification process. In many situations and for a variety of reasons, the event trace could be incomplete or could contain imprecise events. When a missing or ambiguous event is detected, the monitor may be unable to deliver a sound verdict. In this survey, we review the literature dealing with the problem of monitoring with incomplete traces. We list the different causes of uncertainty that have been identified, and analyze their effect on the monitoring process. We identify and compare the different methods that have been proposed to perform monitoring on such traces, highlighting the advantages and drawbacks of each method

Runtime Verification Under Access Restrictions

We define a logical framework that permits runtime verification to take place when a monitor has incomplete or uncertain information about the underlying trace. Uncertainty is modeled as a stateful access control proxy that has the capacity to turn events into sets of possible events, resulting in what we call a "multi-trace". We describe a model of both proxy and monitor as extensions of Mealy machines, and provide an algorithm to lift a classical monitor into a sound, loss-tolerant monitor. Experiments on various scenarios show that the approach can account for various types of data degradation and access limitations, provides a tighter verdict than existing works in some cases, and preserves scalable performance of the model

A modular runtime enforcement model using multi-traces

Runtime enforcement seeks to provide a valid replacement to any misbehaving sequence of events of a running system so that the correct sequence complies with a user-defined security policy. However, depending on the capabilities of the enforcement mechanism, multiple possible replacement sequences may be available, and the current literature is silent on the question of how to choose the optimal one. In this paper, we propose a new model of enforcement monitors, that allows the comparison between multiple alternative corrective enforcement actions and the selection of the optimal one, with respect to an objective user-defined gradation, separate from the security policy. These concepts are implemented using the event stream processor BeepBeep and a use case is presented. Experimental evaluation shows that our proposed framework can dynamically select enforcement actions at runtime, without the need to manually define an enforcement monitor

Distinct patterns of expression of traumatic brain injury biomarkers after blast exposure: Role of compromised cell membrane integrity

Glial fibrillary acidic protein (GFAP), a protein enriched in astrocytes, and Tau, a protein abundant inneuronal microtubules, are being widely studied as biomarkers of brain injury, and persistent severity-dependent increases in brain and blood have been reported. Studies on the acute changes of these proteinsafter blast exposure are limited. Using a mouse model of closely-coupled repeated blast exposures, wehave evaluated acute changes in the levels of GFAP and total Tau by Western blotting. Brain levels of GFAPand Tau proteins decreased significantly at 6 h and increased considerably at 24 h after repeated blastexposures. Plasma samples showed a similar initial decrease and later increase over this timeframe. Thisbiphasic pattern points to possible absorption or sequestration of these proteins from plasma immedi-ately after repeated blast exposures. Liver and spleen tissue showed significant increases in the levelsof GFAP and Tau protein at 6 and 24 h post-blast exposures whereas semi-quantitative RT-PCR analysisof liver showed no significant changes in the levels of GFAP or Tau mRNAs. These results suggest thatblast exposure causes transient changes in cell membrane integrity in multiple organs leading to abnor-mal migration of proteins from the tissues to the plasma and vice versa. This transient changes in cellmembrane permeability and subsequent bidirectional movement of molecules may contribute to thepathophysiology of TBI and polytrauma after blast exposure

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A modular pipeline for enforcement of security properties at runtime

Runtime enforcement ensures the respect of a user-specified security policy by a program by providing a valid replacement for any misbehaving sequence of events that may occur during that program’s execution. However, depending on the capabilities of the enforcement mechanism, multiple possible replacement sequences may be available, and the current literature is silent on the question of how to choose the optimal one. Furthermore, the current design of runtime monitors imposes a substantial burden on the designer, since the entirety of the monitoring task is accomplished by a monolithic construct, usually an automata-based model. In this paper, we propose a new modular model of enforcement monitors, in which the tasks of altering the execution, ensuring compliance with the security policy, and selecting the optimal replacement are split into three separate modules, which simplifies the creation of runtime monitors. We implement this approach by using the event stream processor BeepBeep and a use case is presented. Experimental evaluation shows that our proposed framework can dynamically select an adequate enforcement actions at runtime, without the need to manually define an enforcement monitor

Minocycline and the SPR741 Adjuvant Are an Efficacious Antibacterial Combination for Acinetobacter baumannii Infections

Antibiotic resistance, when it comes to bacterial infections, is not a problem that is going to disappear anytime soon. With the lack of larger investment in novel antibiotic research and the ever-growing increase of resistant isolates amongst the ESKAPEE pathogens (Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus sp., and Escherichia coli), it is inevitable that more and more infections caused by extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains will arise. One strategy to counteract the growing threat is to use antibiotic adjuvants, a drug class that on its own lacks significant antibiotic activity, but when mixed with another antibiotic, can potentiate increased killing of bacteria. Antibiotic adjuvants have various mechanisms of action, but polymyxins and polymyxin-like molecules can disrupt the Gram-negative outer membrane and allow other drugs better penetration into the bacterial periplasm and cytoplasm. Previously, we showed that SPR741 had this adjuvant effect with regard to rifampin; however, rifampin is often not used clinically because of easily acquired resistance. To find additional, appropriate clinical partners for SPR741 with respect to pulmonary and wound infections, we investigated tetracyclines and found a previously undocumented synergy with minocycline in vitro and in vivo in murine models of infection

Longitudinal temperature measurement can determine humane endpoints in BALB/c mouse models of ESKAPEE infection

ABSTRACTAntimicrobial resistance (AMR) is a worldwide problem, which is driving more preclinical research to find new treatments and countermeasures for drug-resistant bacteria. However, translational models in the preclinical space have remained static for years. To improve animal use ethical considerations, we assessed novel methods to evaluate survival after lethal infection with ESKAPEE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, and Escherichia coli) in pulmonary models of infection. Consistent with published lung infection models often used for novel antimicrobial development, BALB/c mice were immunosuppressed with cyclophosphamide and inoculated intranasally with individual ESKAPEE pathogens or sterile saline. Observations were recorded at frequent intervals to determine predictive thresholds for humane endpoint decision-making. Internal temperature was measured via implanted IPTT300 microchips, and external temperature was measured using a non-contact, infrared thermometer. Additionally, clinical scores were evaluated based on animal appearance, behaviour, hydration status, respiration, and body weight. Internal temperature differences between survivors and non-survivors were statistically significant for E. faecium, S. aureus, K. pneumoniae, A. baumannii, E. cloacae, and E. coli, and external temperature differences were statistically significant for S. aureus, K. pneumoniae, E. cloacae, and E. coli. Internal temperature more precisely predicted mortality compared to external temperature, indicating that a threshold of 85ºF (29.4ºC) was 86.0% predictive of mortality and 98.7% predictive of survival. Based on our findings, we recommend future studies involving BALB/c mice ESKAPEE pathogen infection use temperature monitoring as a humane endpoint threshold

Radiation-Inactivated Acinetobacter baumannii Vaccine Candidates

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection

Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine Candidates

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection