Pilot and Controller Evaluations of Separation Function Allocation in Air Traffic Management

Two human-in-the-loop simulation experiments were conducted in coordinated fashion to investigate the allocation of separation assurance functions between ground and air and between humans and automation. The experiments modeled a mixed-operations concept in which aircraft receiving ground-based separation services shared the airspace with aircraft providing their own separation service (i.e., self-separation). Ground-based separation was provided by air traffic controllers without automation tools, with tools, or by ground-based automation with controllers in a managing role. Airborne self-separation was provided by airline pilots using self-separation automation enabled by airborne surveillance technology. The two experiments, one pilot-focused and the other controller-focused, addressed selected key issues of mixed operations, assuming the starting point of current-day operations and modeling an emergence of NextGen technologies and procedures. In the controller-focused experiment, the impact of mixed operations on controller performance was assessed at four stages of NextGen implementation. In the pilot-focused experiment, the limits to which pilots with automation tools could take full responsibility for separation from ground-controlled aircraft were tested. Results indicate that the presence of self-separating aircraft had little impact on the controllers' ability to provide separation services for ground-controlled aircraft. Overall performance was best in the most automated environment in which all aircraft were data communications equipped, ground-based separation was highly automated, and self-separating aircraft had access to trajectory intent information for all aircraft. In this environment, safe, efficient, and highly acceptable operations could be achieved for twice today's peak airspace throughput. In less automated environments, reduced trajectory intent exchange and manual air traffic control limited the safely achievable airspace throughput and negatively impacted the maneuver efficiency of self-separating aircraft through high-density airspace. In a test of scripted conflicts with ground-managed aircraft, flight crews of self-separating aircraft prevented separation loss in all conflicts with detection time greater than one minute. In debrief, pilots indicated a preference for at least five minute's alerting notice and trajectory intent information on all aircraft. When intent information on ground-managed aircraft was available, self-separating aircraft benefited from fewer conflict alerts and fewer required deviations from trajectory-based operations

Effects of MDM2, MDM4 and TP53 Codon 72 Polymorphisms on Cancer Risk in a Cohort Study of Carriers of TP53 Germline Mutations

Previous studies have shown that MDM2 SNP309 and p53 codon 72 have modifier effects on germline P53 mutations, but those studies relied on case-only studies with small sample sizes. The impact of MDM4 polymorphism on tumor onset in germline mutation carriers has not previously been studied.We analyzed 213 p53 germline mutation carriers including 168(78.9%) affected with cancer and 174 who had genotypic data. We analyzed time to first cancer using Kaplan-Meier and Cox proportional hazards methods, comparing risks according to polymorphism genotypes. For MDM2 SNP309, a significant difference of 9.0 years in the average age of cancer diagnosis was observed between GG/GT and TT carriers (18.6 versus 27.6 years, P = 0.0087). The hazards ratio was 1.58 (P = 0.03) comparing risks among individuals with GG/GT to risk among TT, but this effect was only significant in females (HR = 1.60, P = 0.02). Compared to other genotypes, P53 codon 72 PP homozygotes had a 2.24 times (P = 0.03) higher rate for time to develop cancer. We observed a multiplicative joint effect of MDM2 and p53 codon72 polymorphism on risk. The MDM4 polymorphism had no significant effects.Our results suggest that the MDM2 SNP309 G allele is associated with cancer risk in p53 germline mutation carriers and accelerates time to cancer onset with a pronounced effect in females. A multiplicative joint effect exists between the MDM2 SNP309 G allele and the p53 codon 72 G allele in the risk of cancer development. Our results further define cancer risk in carriers of germline p53 mutations