Advanced global optimisation for mission analysis and design

This report describes the analysis and development of novel tools for the global optimisation of relevant mission design problems. A taxonomy was created for mission design problems, and an empirical analysis of their optimisational complexity performed - it was demonstrated that the use of global optimisation was necessary on most classes and informed the selection of appropriate global algorithms. The selected algorithms were then applied to the di®erent problem classes: Di®erential Evolution was found to be the most e±cient. Considering the speci¯c problem of multiple gravity assist trajectory design, a search space pruning algorithm was developed that displays both polynomial time and space complexity. Empirically, this was shown to typically achieve search space reductions of greater than six orders of magnitude, thus reducing signi¯cantly the complexity of the subsequent optimisation. The algorithm was fully implemented in a software package that allows simple visualisation of high-dimensional search spaces, and e®ective optimisation over the reduced search bounds.

Increases in prefrontal cortex activity when regulating negative emotion predicts symptom severity trajectory over six months in depression

Context: Emotion regulation is critically disrupted in depression and use of paradigms tapping these processes may uncover essential changes in neurobiology during treatment. In addition, as neuroimaging outcome studies of depression commonly utilize solely baseline and endpoint data – which is more prone to week-to week noise in symptomatology – we sought to use all data points over the course of a six month trial. Objective: To examine changes in neurobiology resulting from successful treatment. Design: Double-blind trial examining changes in the neural circuits involved in emotion regulation resulting from one of two antidepressant treatments over a six month trial. Participants were scanned pretreatment, at 2 months and 6 months posttreatment. Setting: University functional magnetic resonance imaging facility. Participants: 21 patients with Major Depressive Disorder and without other Axis I or Axis II diagnoses and 14 healthy controls. Interventions: Venlafaxine XR (doses up to 300mg) or Fluoxetine (doses up to 80mg). Main Outcome Measure: Neural activity, as measured using functional magnetic resonance imaging during performance of an emotion regulation paradigm as well as regular assessments of symptom severity by the Hamilton Rating Scale for Depression. To utilize all data points, slope trajectories were calculated for rate of change in depression severity as well as rate of change of neural engagement. Results: Those depressed individuals showing the steepest decrease in depression severity over the six months were those individuals showing the most rapid increases in BA10 and right DLPFC activity when regulating negative affect over the same time frame. This relationship was more robust than when using solely the baseline and endpoint data. Conclusions: Changes in PFC engagement when regulating negative affect correlate with changes in depression severity over six months. These results are buttressed by calculating these statistics which are more reliable and robust to week-to-week variation than difference scores.