The Effectiveness of a Route Crossing Tool in a Simulated New York Airspace

Congested airspace is the cause of many delays in the terminal area and these delays can have a ripple effect on the rest of a nation's airspace. The New York terminal area is an example of where this happens in the U. S. An important goal, therefore, is to increase the efficiency of operations in congested terminal airspace where possible. Modeling studies of arrival and departure flows have shown that sharing of arrival and departure airspace increases efficiency in terminal operations. One source of inefficiency in terminal operations is that departure aircraft are frequently held level under arrival flows when it would be more efficient to climb the departure aircraft earlier. A Route Crossing Tool was developed to help controllers climb Newark (EWR) departures to the south earlier by temporarily sharing airspace with arrivals coming into LaGuardia (LGA) from the south. Instead of flying under the arrivals, a departure to the south could climb earlier by flying through the arrival airspace if there was a suitable gap between arrivals. A Human-in-the-Loop (HITL) simulation was conducted in this environment which compared three tool conditions: Baseline (no tool), a Single Route Crossing tool in which one route through the arrival flow was evaluated for crossing, and a Multi-Route Crossing tool in which five parallel routes were evaluated. In all conditions, the departures could be held level under the arrival flow. The results showed that controllers climbed a higher proportion of departures in the Multi-Route tool condition than in the other two conditions, with a higher proportion of departures climbed in smaller gaps and in front of trailing arrivals. The controllers indicated that the Multi-Route and Single Route tools helped them estimate distances more accurately and rated safety, workload, and coordination in the simulation as acceptable

Development of a Route Crossing Tool for Shared Airspace Environments

In current-day Terminal Radar Approach Control (TRACON) operations, departure and arrival controllers maintain separate and dedicated airspace for their respective traffic flows. Although this practice has obvious safety features, it also leads to inefficiencies; for example, departure aircraft may be routinely capped beneath arrival airspace. With the right decision-support and coordination tools, departures could continue to climb through arrival airspace when sufficient gaps exist. Previous studies of shared airspace have examined pre-arranged coordination procedures, as well as tools that gave feedback to the controllers on where gaps between arrivals were located and whether the departure aircraft could be scheduled to fly through those gaps [1, 2, 3, 4]. Since then, the Route Crossing Tool (RCT) has been developed to allow controllers to assess multiple pre-defined route options at points where the arrivals and departures cross, thereby increasing the possibility of climbing a departure through an arrival gap.The RCT aids in ensuring lateral separation between departure and arrival aircraft that pass through the same altitude. Since the RCT can be applied tactically, it can enable aircraft to fly through arrival flows even if these aircraft depart outside scheduled times. The RCT makes use of a set of predefined parallel departure routes crossing the arrival flow at equidistant intersecting points on the arrival route. The RCT uses the Estimated Time of Arrival (ETA) of the departure aircraft at each intersecting point to calculate the lateral separation with the neighboring arrivals when it crosses that point; this information is graphically displayed to the controller. Additionally, the RCT incorporates forecast winds in its ETA predictions.Multiple prototypes of the RCT have been iteratively developed with feedback from Subject Matter Experts (SMEs). This paper presents the final design, the design process, and lessons learned. Initial results from a simulation suggest that the tool was successful in helping controllers to safely climb more aircraft. Controller feedback on the tool was also positive

Design, Formulation, and Evaluation of Novel Dissolving Microarray Patches Containing Rilpivirine for Intravaginal Delivery

Antiretroviral (ARV) drugs have, for many years, been studied and administered in the prevention and treatment of human immunodeficiency virus (HIV). Intramuscular (IM) injection of long acting (LA) ARVs are in clinical development, but injectable formulations require regular access to healthcare facilities and disposal facilities for sharps. The development of a discrete, self‐administered, and self‐disabling vehicle to deliver ARVs could obviate these issues. This study describes the formulation, mechanical characterization, and in vivo evaluation of dissolving microarray patches (MAPs) containing a LA nanosuspension of the ARV, rilpivirine (RPV, RPV LA), for vaginal delivery. This is the first study to apply MAPs into vaginal tissue. The RPV LA MAPs penetrate ex vivo skin and a synthetic vaginal skin model and withstand the effects of potential dragging motion across synthetic vaginal epithelium. In in vivo studies, the mean plasma concentration of RPV in rats at the 56 day endpoint (116.5 ng mL−1) is comparable to that achieved in the IM control cohort (118.9 ng mL−1). RPV is detected systemically, in lymph and vaginal tissue, indicating the potential to deliver RPV LA to primary sites of viral challenge and replication. This innovative research has future potential for patients and healthcare workers, particularly in low‐resource settings

Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells

Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an ‘immature’ neonatal to a ‘mature’ adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation

Regulation of Coronary Blood Flow

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. © 2017 American Physiological Society. Compr Physiol 7:321-382, 2017

Canine Distemper Virus in Wildlife: Knowledge and Gaps in Understanding

Canine distemper virus (CDV) is a highly contagious respiratory pathogen that infects a broad range of terrestrial carnivores with documented spillover into marine mammals. The virus is particularly prevalent in urban wildlife, but the transmission dynamics that maintain the virus in wildlife are unclear. We conducted a survey of the literature to summarize what is known about CDV in wildlife and to identify gaps and biases in our understanding of this virus. Though CDV is well characterized in dogs, gaps and biases limit our understanding about CDV in wildlife including how the virus evolves within and between hosts. We present two original contributions that aim to address these gaps in knowledge – a proposed study to evaluate a commercially available lateral flow diagnostic for use in raccoons and the results of an initial study to look at signatures of positive selection in each of the proteins CDV encodes. A sensitive and specific point of care diagnostic could be used at wildlife rehabilitation centers, not only to potentially prevent unnecessary euthanasia of an uninfected animal, but also to identify infected animals for further testing of wildtype viral genomes. The results of our positive selection study indicate that additional proteins encoded by CDV, beyond the hemagglutinin and fusion proteins, which are commonly cited in the literature, may also be under positive selection pressure. These results indicate more detailed studies may be warranted for a deeper understanding of selection pressures on the virus