Long-term socioeconomic outcome following surgical intervention in the treatment of refractory epilepsy in childhood and adolescence

Surgical treatment of refractory epilepsy in childhood and adolescence has been shown to be effective in reducing the seizure frequency. This paper examines the question: "Does this result in a better socioeconomic outcome in later years?" Patients who underwent a surgical procedure for the treatment of their medically refractory epilepsy at our hospital, had more than 2-years' follow-up, and were less than 18 years old at time of survey were included. From a retrospective chart review, age at onset and at surgery, duration of seizures prior to surgery, years of follow-up, type of surgery, and neurological status were obtained. From a telephone survey, seizure frequency after surgery, marital, financial and driving status, level of education, and employment status were ascertained. Sixty-four patients in our epileptic surgical series meet entry criteria. Significantly higher levels of education, employment status and independence were found in patients with a class I Engel outcome compared to other Engel outcomes.     

Virtual planning in patients with frontal lobe lesions

The VIrtual Planning Test (VIP) was developed to investigate the planning and organisational abilities of 25 patients with frontal lobe neurosurgical lesions, comparing their performance with 25 matched control subjects. The task, presented in the form of a board game, simulates planning and execution of a set of target activities that have to take place over a four day period, involving those that are either preparatory for a fictional "trip" abroad, or those that relate to the subject's current environment (context). The frontal lobe patients were impaired overall, tending to select inappropriate activities associated with their current context and showing greater impairment on subtasks requiring only one, rather than two, preparatory acts. The findings are discussed in terms of the validity of the VIP test in identifying executive functioning impairment and the degree to which the pattern of deficits are consistent with neuropsychological models of executive function.     

Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13

The extraocular fibrosis syndromes are congenital ocular-motility disorders that arise from dysfunction of the oculomotor, trochlear, and abducens nerves and/or the muscles that they innervate. Each is marked by a specific form of restrictive paralytic ophthalmoplegia with or without ptosis. Individuals with the classic form of congenital fibrosis of the extraocular muscles (CFEOM1) are born with bilateral ptosis and a restrictive infraductive external ophthalmoplegia. We previously demonstrated that CFEOM1 is caused by an autosomal dominant locus on chromosome 12 and results from a developmental absence of the superior division of the oculomotor nerve. We now have mapped a variant of CFEOM, exotropic strabismus fixus ("CFEOM2"). Affected individuals are born with bilateral ptosis and restrictive ophthalmoplegia with the globes "frozen" in extreme abduction. This autosomal recessive disorder is present in members of three consanguineous Saudi Arabian families. Genetic analysis of 70 individuals (20 affected individuals) reveals linkage to markers on chromosome 11q13, with a combined LOD score of 12.3 at the single nonrecombinant marker, D11S1314. The 2.5-cM CFEOM2 critical region is flanked by D11S4196/D11S4162 and D11S4184/1369. Two of the three families share a common disease-associated haplotype, suggesting a founder effect for CFEOM2. We hypothesize that CFEOM2 results from an analogous developmental defect to CFEOM1, one that affects both the superior and inferior divisions of the oculomotor nerve and their corresponding alpha motoneurons and extraocular muscles.     

Binding and lysing of blood clots using MRX-408

RATIONALE AND OBJECTIVES: A thrombus-specific ultrasound contrast agent, MRX-408, has been developed recently. This agent consists of phospholipid-coated microbubbles with a ligand capable of targeting the GPIIb/IIIa receptor, thereby allowing the microbubbles to bind with thrombi rich in activated platelets. In vitro and in vivo animal experiments have been conducted to examine imaging enhancement and sonothrombolysis using this agent compared with a nontargeted agent. METHODS: For clot binding, blood-smeared slides were incubated with microbubbles and examined under a light microscope. Change in backscatter signals from the blood clots after binding was examined by both an ultrasound scanner and two single-element transducers arranged in a transmitter-receiver pair. For clot lysis, either 1-MHz or 20-KHz ultrasound was used to enhance the lysing effects of MRX-408 with or without urokinase. RESULTS: Evidence of binding was demonstrated under a microscope. In vitro experiments showed that the "acoustic signature", or properties, of blood clots changed after binding. Clots became more echogenic and nonlinear. In vivo fundamental ultrasound imaging confirmed that as a result of binding, blood clots were more visible, the area of detection was improved, and shadowing behind clots was more noticeable. Under 1-MHz ultrasound and 30 minutes of treatment, lysis efficiency reached 34% with MRX-408, whereas there was no visible clot lysis with saline. CONCLUSION: The results of these preliminary studies show that as a contrast agent, MRX-408 enhanced clots under ultrasound imaging and facilitated sonothrombolysis with or without thrombolytic drugs.     

Optimizing latency and throughput of application workflows on clusters

Scheduling, in many application domains, involves optimization of multiple performance metrics. For example, application workflows with real-time constraints have strict throughput requirements and also desire a low latency or response time. In this paper, we present a novel algorithm for the scheduling of workflows that act on a stream of input data. Our algorithm focuses on the two performance metrics, latency and throughput, and minimizes the latency of workflows while satisfying strict throughput requirements. We also describe steps to use the above approach to solve the problem of meeting latency requirements while maximizing throughput. We leverage pipelined, task and data parallelism in a coordinated manner to meet these objectives and investigate the benefit of task duplication in alleviating communication overheads in the pipelined schedule for different workflow characteristics. The proposed algorithm is designed for a realistic bounded multi-port communication model, where each processor can simultaneously communicate with at most k distinct processors. Experimental evaluation using synthetic benchmarks as well as those derived from real applications shows that our algorithm consistently produces lower latency schedules that meet throughput requirements, even when previously proposed schemes fail.     

Reconstruction of cellular biological structures from optical microscopy data

Developments in optical microscopy imaging have generated large high-resolution data sets that have spurred medical researchers to conduct investigations into mechanisms of disease, including cancer at cellular and subcellular levels. The work reported here demonstrates that a suitable methodology can be conceived that isolates modality-dependent effects from the larger segmentation task and that 3D reconstructions can be cognizant of shapes as evident in the available 2D planar images. In the current realization, a method based on active geodesic contours is first deployed to counter the ambiguity that exists in separating overlapping cells on the image plane. Later, another segmentation effort based on a variant of Voronoi tessellations improves the delineation of the cell boundaries using a Bayesian formulation. In the next stage, the cells are interpolated across the third dimension thereby mitigating the poor structural correlation that exists in that dimension. We deploy our methods on three separate data sets obtained from light, confocal, and phase-contrast microscopy and validate the results appropriately.     

Smooth muscle cell to elastic lamina connections in developing mouse aorta. Role in aortic medial organization

BACKGROUND: The structural and functional intigration of smooth muscle cells and elastic laminae in the aortic media is not well established. Detailed information concerning normal ultrastructural features of the aortic media will provide a better understanding of the medial changes that occur in vascular diseases such as hypertension and aortic aneurysms. EXPERIMENTAL DESIGN: The ultrastructural development and organization of connections between smooth muscle cells and elastic laminae in the mouse aortic media were studied by light and electron microscopy. RESULTS: Early in development, the smooth muscle cells become linked to the elastic laminae by bundles of microfibrils. These microfibrils become progressively infiltrated with elastin so as to form extensions of elastin from the elastic laminae in the adult media. Each elastin extension spans obliquely from the elastic lamina to the surface of the smooth muscle cell where it attaches in a region of membrane occupied by an intracellular membrane-associated dense plaque. On the cytoplasmic face of the plaque, a contractile filament bundle penetrates and anchors in an orientation similar to that of the extracellular elastin extension. The contractile filament bundle traverses the cell obliquely and anchors in a dense plaque on the opposite side of the cell that is in turn linked to the next elastic lamina by another elastin extension. The extracellular elastin extensions and the intracellular contractile filament bundles thus form a "contractile-elastic unit," a continuous line of structures that links adjacent elastic laminae. The oblique orientation of the contractile-elastic units reverses direction in successive smooth muscle cell layers in a herringbone-like pattern. Thus, tension transmitted to one elastic lamina by the smooth muscle cells on either side results in a uniform force exerted on the elastic lamina in one circumferential direction, that on the adjacent elastic laminae being in the opposite direction. CONCLUSIONS: Results from this study demonstrate the presence of smooth muscle cell to elastic lamina connections that form early in development as contractile-elastic units; basic units of aortic medial ultrastructure. The overall organization of the contractile-elastic units within the aortic media is proposed to provide a means for coordinating contractile and elastic tensions in response to mechanical stresses imposed on the vessel wall.     

Recasting Florida's insanity defense. Two modest proposals

Three states have established psychiatric security review boards mandated to primarily provide protection from the potentially destructive behavior of insanity acquitees. Each year in Florida there are 100 of these patients; 5% have been involved in capital offenses. These boards, as compared with the extant judiciary system, are more effective and parsimonious and serve the end of primary prevention. It is recommended that the plea, "not guilty by reason of insanity," be changed to "guilty but insane." The change is largely semantic but should result in greater prosecutorial and public acceptance of the insanity plea and be more in keeping with individual freedom for patients as provided under the Constitution.     

Scalability analysis of declustering methods for multidimensionalrange queries

Efficient storage and retrieval of multi-attribute data sets has become one of the essential requirements for many data-intensive applications. The Cartesian product file has been known as an effective multi-attribute file structure for partial-match and best-match queries. Several heuristic methods have been developed to decluster Cartesian product files across multiple disks to obtain high performance for disk accesses. Although the scalability of the declustering methods becomes increasingly important for systems equipped with a large number of disks, no analytic studies have been done so far. The authors derive formulas describing the scalability of two popular declustering methods-Disk Module and Fieldwise Xor-for range queries, which are the most common type of queries. These formulas disclose the limited scalability of the declustering methods, and this is corroborated by extensive simulation experiments. From the practical point of view, the formulas given in the paper provide a simple measure that can be used to predict the response time of a given range query and to guide the selection of a declustering method under various conditions