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BACKGROUND Constitutional Mismatch Repair Deficiency (CMMRD) is a cancer predisposition syndrome caused by biallelic mutations in the mismatch repair pathway, and high-grade glioma (HGG) constitute the most prevalent brain tumours. Pseudoprogression alludes to radiological changes that mimic tumour progression, but are in fact due to other causes such as therapy related inflammation. It can occur as early as three months post treatment. To our knowledge, its characteristics in CMMRD patients has not been reported. METHODS We retrospectively identified seven patients with CMMRD and history of HGG at The Royal Children’s Hospital, Melbourne from 2005 to 2019. Our objective was to review the characteristics of pseudoprogression in this cohort. RESULTS Out of the seven patients, two with constitutional loss of PMS2 demonstrated evidence of pseudoprogression. Patient 1 presented at 16 years old with a cerebellar anaplastic astrocytoma. She developed clinical and radiological progression within two weeks of starting radiotherapy, persisting up to four months after completion. However, six months post radiation she improved without intervention and the tumour remains stable five years post therapy. Patient 2 presented at 17 years old with a midbrain anaplastic astrocytoma, and showed signs of progression four weeks after completion of radiotherapy. She was then treated with Bevacizumab, an anti-VEGFA antibody with remarkable response. She subsequently received Nivolumab, a checkpoint inhibitor with ongoing stable disease for four months. CONCLUSION Our findings showed that pseudoprogression can occur early in the treatment course in CMMRD patients. Identification of this entity is important for appropriate clinical management.

Previous studies have shown that a chromatic mechanism can drive pupil responses. The aim of this research was to clarify whether a linear or non-linear chromatic mechanism drives pupillary responses by using various colours of test stimuli defined in cone-contrast space. Pupil and accommodation responses evoked by these test stimuli were continuously and simultaneously measured objectively by photorefraction. The results with isochromatic and isoluminant stimuli showed that the accommodative level remained approximately constant (<0.25D change in mean level) even when the concurrent pupillary responses was large (~0.30mm). The pupillary response to an isoluminant grating was sustained, delayed (by ~60ms) and larger in amplitude than that for a isochromatic uniform stimulus, which supports previous work suggesting that the chromatic mechanism contributes to the pupillary response. In a second experiment, selected chromatic test gratings were utilized and iso-response contours in cone-contrast space were obtained. The results showed that the iso-response contour in cone contrast space is well described (r^2=0.99) by a straight line with a positive slope. The results indicate that a L-M linear chromatic mechanism, whereby a signal from the Long-wavelength cone (L-cone) is subtracted from that of the Middle-wavelength cone (M-cone) and vice versa, drives pupillary responses.

Minehunting is a complex process involving detection and classification of contacts using sonar and the subsequent identification and disposal of mines generally using a remotely operated underwater vehicle (ROV). However, making suitable assumptions, minehunting can be approximated by a series of connected events and thus made amenable to modelling using the technique of discrete-event simulation. In this report, a discrete-event minehunting simulation model is described together with instructions for its operation. The model can be applied to evaluate the effectiveness of minehunting systems for a given operational scenario and also to investigate new concepts. (AN)