Implementation and applications of EMOD, an individual-based multi-disease modeling platform.

Individual-based models provide modularity and structural flexibility necessary for modeling of infectious diseases at the within-host and population levels, but are challenging to implement. Levels of complexity can exceed the capacity and timescales for students and trainees in most academic institutions. Here we describe the process and advantages of a multi-disease framework approach developed with formal software support. The epidemiological modeling software, EMOD, has undergone a decade of software development. It is structured so that a majority of code is shared across disease modeling including malaria, HIV, tuberculosis, dengue, polio and typhoid. In additional to implementation efficiency, the sharing increases code usage and testing. The freely available codebase also includes hundreds of regression tests, scientific feature tests and component tests to help verify functionality and avoid inadvertent changes to functionality during future development. Here we describe the levels of detail, flexible configurability and modularity enabled by EMOD and the role of software development principles and processes in its development.

Prevention of visual loss caused by shunt failure: a potential role for optic nerve sheath fenestration. Report of three cases.

Ophthalmological problems such as papilledema, loss of visual acuity, and oculomotor palsies are common in patients with shunt malfunctions. The authors report on three patients with shunts who presented with visual loss. In each case, the diagnosis of shunt malfunction was delayed because other classic signs and symptoms of intracranial hypertension were absent. All three patients underwent optic nerve sheath fenestration (ONSF) with resultant stabilization or improvement of visual symptoms before the shunt malfunction was recognized and treated. Consideration of these cases suggests a potential protective role of ONSF for patients with shunt malfunction.

Surgical quality assurance in the Ischemic Optic Neuropathy Decompression Trial (IONDT).

The purpose of this article is to report the methods and results of the surgical quality assurance program associated with the Ischemic Optic Neuropathy Decompression Trial (IONDT). A surgical quality assurance committee developed and implemented a quality assurance program for a randomized clinical trial requiring surgical intervention. A surgical technique questionnaire was administered at two times during the study course, and maintenance of surgeon certification required submission and approval of a masked videotape of an optic nerve sheath decompression surgery by each study surgeon. Surgical quality was assessed through completion of surgical report forms and standardized, masked review of operative notes. Rates of compliance and intra- and interreviewer agreement were assessed for each aspect of the program. Twenty-five of 32 surgeons (81%) successfully completed and maintained certification. Item agreement varied from 21-92% among reviewers of satisfactory videotapes and 22-89% on unsatisfactory videotapes. Intrarater agreement for videotape acceptability was 11 of 13 (85%), and for specific surgical steps, 147 of 182 (81%). Operative notes were submitted for 123 of 125 (98%) patients receiving surgery. Interrater agreement on individual items ranged from 73-100%. Classification of individual items was identical on first and second review for 1285 of 1344 (95.6%) items. Overall agreement for individual reviewers was 93.8-97.8%. We conclude that use of a small peer review committee, which developed and oversaw a quality assurance program, allowed for consistent certification and monitoring of surgical performance. This in turn increased the credibility of the IONDT results, which demonstrated no difference in outcome between operated and unoperated groups of patients.

A functional magnetic resonance imaging study in patients with benign essential blepharospasm.

OBJECTIVE To identify blinking-induced functional magnetic resonance imaging (fMRI) activation patterns in five benign essential blepharospasm (BEB) patients and five age-matched control subjects. METHODS fMRI brain activation maps were obtained during repeated conditions of spontaneous and voluntary blinking in BEB and control groups. Blood oxygen level-dependent intensity images were collected from two separate runs as 16 axial and 16 coronal, 8 mm thick slices using a T2-star weighted gradient echo EPI sequence, coregistered with anatomic images. Spatially normalized and isotropically blurred activation maps for each subject were combined within groups of BEB patients and control subjects to generate maps of the intersubject mean fractional signal change.RESULTS Substantially greater activation during spontaneous and voluntary blinking was seen in BEB patients compared with control subjects in the anterior visual cortex, anterior cingulate cortex, primary motor cortex, central region of the thalamus, and superior cerebellum. In both groups, activations were generally greater for voluntary than for spontaneous blinking. CONCLUSIONS The activations observed might represent a hyperactive cortical circuit linking visual cortex, limbic system, supplementary motor cortex, cerebellum, and supranuclear motor pathways innervating the periorbital muscles.

The effect of apomorphine on blink kinematics in subhuman primates with and without facial nerve palsy.

PURPOSE: The purpose of this study was to document the effect of acutely delivered apomorphine, a dopamine receptor agonist with both D1 and D2 properties, on blink rate and the amplitude-velocity characteristics of eyelid kinematics in a group of nonhuman primates. METHODS: Three cynomolgus and two rhesus macaques underwent baseline recordings for eyelid kinematics, using the Robinson search coil technique. Next, each animal received a 0.15-mg/kg subcutaneous injection of apomorphine. Recordings were taken at 45 and 90 minutes, respectively, after injection. Blink rates per minute were obtained, and main sequence relationships were calculated for every animal. The data were pooled for each eyelid, excluding one monkey who was affected by facial nerve palsy and was analyzed separately. RESULTS: Monkeys with normal facial musculature and normal baseline blink rates showed consistently longer, faster blinks after apomorphine. The main sequence relationship, although tending to be lower, was not statistically different from baseline. One monkey, with prior facial nerve palsy and a very steep amplitude versus peak velocity relationship, showed normalization of the main sequence slope after apomorphine at both 45 and 90 minutes after injection. CONCLUSIONS: Apomorphine consistently lowers blink rate and changed blink metrics in normal monkeys and, more dramatically, in a monkey with facial nerve palsy. These findings add credence to models in which dopamine deficiency plays a role in the modulation of blink kinematics.