Resilience Engineering’s Potential For Advanced Air Mobility (AAM)

The national airspace (NAS) will rapidly evolve in the next ten to twenty years. Plans for Advanced Air Mobility (AAM) during that period envision highly automated airspace management systems and electrically powered vehicles. AAM concepts also anticipate limited human roles. The goal of limiting the human role is to minimize the potential for misadventures, yet how the human role is limited needs to be carefully considered in order to also preserve the potential for human successes. The field of resilience engineering (RE) focuses on how systems can change in order to seize an opportunity or withstand an unforeseen challenge. RE methods rely on the use of empirical data to optimize the ability of any system to adapt. RE studies have shown how individual and team initiatives ensure resilient system performance by creating safety through flexibility. Benefits of the RE approach include improved awareness of operational circumstances and how system elements depend on each other, and the ability to allocate limited resources and prepare for surprise. RE offers the ability to account for and incorporate the human role as an essential element in order to ensure NAS systems’ resilient performance. Data on the human contribution to safe and resilient system performance, which is termed “work as done,” are available but are not being considered as the NAS evolves. We present an approach that describes how use of RE can enable the evolving NAS to adapt, and perform, in a resilient manner

How Do Different Knowledge Frameworks Help Us Learn From Aviation Line Observations?

Human performance includes actions that increase safety, as well as actions that can reduce safety. Ensuring safety in complex dynamic operations like commercial aviation depends on the ability to institute appropriate responses based on what is learned from flightcrew performance and the contexts in which it occurs. To do this systemically at the organization level requires collecting data on flightcrew performance, developing effective approaches to analyzing those data, and understanding how to translate what has been learned into policies, procedures, and practice. Systematic observation of front-line operators is a vital source of human performance data. Much has been learned from such observations, including methodological principles. Most observations have been based on a framework focused on managing safety challenges and the ensuing unsafe events. A complementary perspective focuses on flexibility and actions that promote continued safe and effective operation. We consider lessons learned about observational methods from an established framework focused on undesired actions and how these might be extended for a framework focused on desired actions

The Insertion of Human Factors Concerns into NextGen Programmatic Decisions

Since the costs of proposed improvements in air traffic management exceed available funding, FAA decision makers must select and prioritize what actually gets implemented. We discuss a set of methods to help forecast operational and human performance issues and benefits before new automation is introduced. This strategy could minimize the impact of politics, assist decision makers in selecting and prioritizing potential improvements, make the process more transparent and strengthen the link between the engineering and human factors domains

How Thoroughly Do Proposed Nextgen Mid-Term Operational Improvements Address Existing Threats?

The goals of the Federal Aviation Administration’s (FAA) Next Generation Air Transportation System (NextGen) include improved safety, increased capacity, increased efficiency, and reduced environmental impact. The FAA has developed 46 mid-term Operational Improvements (OIs) to facilitate initial realization of these benefits in the 2015 – 2018 timeframe. These OIs describe changes in technologies, policies and procedures from current-day air and ground operations designed to mitigate safety, capacity, efficiency, and environmental issues. The main goal of this project was to investigate how thoroughly threats to safety present in today’s operations are addressed by the OIs. These threats, without mitigation, could remain threats in the mid-term, potentially compromising the intended NextGen safety benefits. To address this concern, we extracted threats to safety from 200 Aviation Safety Reporting System incident reports filed by tower air traffic controllers over a five-year period. We then evaluated whether these threats are addressed by the mid-term OIs

An Approach to Quantify Workload in a System of Agents

The role of humans in aviation and other domains continues to shift from manual control to automation monitoring. Studies have found that humans are often poorly suited for monitoring roles, and workload can easily spike in off-nominal situations. Current workload measurement tools, like NASA TLX, use human operators to assess their own workload after using a prototype system. Such measures are used late in the design process and can result in ex- pensive alterations when problems are discovered. Our goal in this work is to provide a quantitative workload measure for use early in the design process. We leverage research in human cognition to de ne metrics that can measure workload on belief-desire-intentions based multi-agent systems. These measures can alert designers to potential workload issues early in design. We demonstrate the utility of our approach by characterizing quantitative differences in the workload for a single pilot operations model compared to a traditional two pilot model

Human Performance Contributions to Safety in Commercial Aviation

In the commercial aviation domain, large volumes of data are collected and analyzed on the failures and errors that result in infrequent incidents and accidents, but in the absence of data on behaviors that contribute to routine successful outcomes, safety management and system design decisions are based on a small sample of non- representative safety data. Analysis of aviation accident data suggests that human error is implicated in up to 80% of accidents, which has been used to justify future visions for aviation in which the roles of human operators are greatly diminished or eliminated in the interest of creating a safer aviation system. However, failure to fully consider the human contributions to successful system performance in civil aviation represents a significant and largely unrecognized risk when making policy decisions about human roles and responsibilities. Opportunities exist to leverage the vast amount of data that has already been collected, or could be easily obtained, to increase our understanding of human contributions to things going right in commercial aviation. The principal focus of this assessment was to identify current gaps and explore methods for identifying human success data generated by the aviation system, from personnel and within the supporting infrastructure

Selecting an Anti-Malarial Clinical Candidate from Two Potent Dihydroisoquinolones

BACKGROUND: The ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. The process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles is described. METHODS: The compounds were tested to define their physicochemical properties including kinetic and thermodynamic solubility, partition coefficient, permeability, ionization constant, and binding to plasma proteins. Metabolic stability was assessed in both microsomes and hepatocytes derived from mice, rats, dogs, and humans. Cytochrome P450 inhibition was assessed using recombinant human cytochrome enzymes. The pharmacokinetic profiles of single intravenous or oral doses were investigated in mice, rats, and dogs. RESULTS: Although both compounds displayed similar physicochemical properties, SJ733 was more permeable but metabolically less stable than SJ311 in vitro. Single dose PK studies of SJ733 in mice, rats, and dogs demonstrated appreciable oral bioavailability (60-100%), whereas SJ311 had lower oral bioavailability (mice 23%, rats 40%) and higher renal clearance (10-30 fold higher than SJ733 in rats and dogs), suggesting less favorable exposure in humans. SJ311 also displayed a narrower range of dose-proportional exposure, with plasma exposure flattening at doses above 200 mg/kg. CONCLUSION: SJ733 was chosen as the candidate based on a more favorable dose proportionality of exposure and stronger expectation of the ability to justify a strong therapeutic index to regulators

Intracellular trafficking, localization, and mobilization of platelet-borne thiol isomerases

OBJECTIVE: Thiol isomerases facilitate protein folding in the endoplasmic reticulum, and several of these enzymes, including protein disulfide isomerase and ERp57, are mobilized to the surface of activated platelets, where they influence platelet aggregation, blood coagulation, and thrombus formation. In this study, we examined the synthesis and trafficking of thiol isomerases in megakaryocytes, determined their subcellular localization in platelets, and identified the cellular events responsible for their movement to the platelet surface on activation. APPROACH AND RESULTS: Immunofluorescence microscopy imaging was used to localize protein disulfide isomerase and ERp57 in murine and human megakaryocytes at various developmental stages. Immunofluorescence microscopy and subcellular fractionation analysis were used to localize these proteins in platelets to a compartment distinct from known secretory vesicles that overlaps with an inner cell-surface membrane region defined by the endoplasmic/sarcoplasmic reticulum proteins calnexin and sarco/endoplasmic reticulum calcium ATPase 3. Immunofluorescence microscopy and flow cytometry were used to monitor thiol isomerase mobilization in activated platelets in the presence and absence of actin polymerization (inhibited by latrunculin) and in the presence or absence of membrane fusion mediated by Munc13-4 (absent in platelets from Unc13dJinx mice). CONCLUSIONS: Platelet-borne thiol isomerases are trafficked independently of secretory granule contents in megakaryocytes and become concentrated in a subcellular compartment near the inner surface of the platelet outer membrane corresponding to the sarco/endoplasmic reticulum of these cells. Thiol isomerases are mobilized to the surface of activated platelets via a process that requires actin polymerization but not soluble N-ethylmaleimide-sensitive fusion protein attachment receptor/Munc13-4-dependent vesicular-plasma membrane fusion

A Core Curriculum in the Biological and Biomedical Sciences for Dentistry

INTRODUCTION: The biomedical sciences (BMS) are a central part of the dental curriculum that underpins teaching and clinical practice in all areas of dentistry. Although some specialist groups have proposed curricula in their particular topic areas, there is currently no overarching view of what should be included in a BMS curriculum for undergraduate dental programmes. To address this, the Association for Dental Education in Europe (ADEE) convened a Special Interest Group (SIG) with representatives from across Europe to develop a consensus BMS curriculum for dental programmes. CURRICULUM: This paper summarises the outcome of the deliberations of this SIG and details a consensus view from the SIG of what a BMS curriculum should include. CONCLUSIONS: Given the broad nature of BMS applied to dentistry, this curriculum framework is advisory and seeks to provide programme planners with an indicative list of topics which can be mapped to specific learning objectives within their own curricula. As dentistry becomes increasingly specialised, these will change, or some elements of the undergraduate curriculum may move to the post-graduate setting. So, this document should be seen as a beginning and it will need regular review as BMS curricula in dentistry evolve