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We apply an optimized method to the adjoint generation of a time-evolving land ice model through algorithmic differentiation (AD). The optimization involves a special treatment of the fixedpoint iteration required to solve the nonlinear stress balance, which differs from a straightforward application of AD software, and leads to smaller memory requirements and in some cases shorter computation times of the adjoint. The optimization is done via implementation of the algorithm of Christianson [1994] for reverse accumulation of fixed-point problems, with the AD tool OpenAD. For test problems, the optimized adjoint is shown to have far lower memory requirements, potentially enabling larger problem sizes on memory-limited machines. In the case of the land ice model, implementation of the algorithm allows further optimization by having the adjoint model solve a sequence of linear systems with identical (as opposed to varying) matrices, greatly improving performance. The methods introduced here will be of value to other efforts applying AD tools to ice models, particularly ones which solve a "hybrid" shallow ice / shallow shelf approximation to the Stokes equations.

West Antarctic Ice Sheet loss is a significant contributor to sea level rise. While the ice loss is thought to be triggered by fluctuations in oceanic heat at the ice shelf bases, ice sheet response to ocean variability remains poorly understood. Using a synchronously coupled ice-ocean model permitting grounding line migration, this study evaluates the response of an ice sheet to periodic variations in ocean forcing. Resulting oscillations in grounded ice volume amplitude is shown to grow as a nonlinear function of ocean forcing period. This implies that slower oscillations in climatic forcing are disproportionately important to ice sheets. The ice shelf residence time offers a critical time scale, above which the ice response amplitude is a linear function of ocean forcing period and below which it is quadratic. These results highlight the sensitivity of West Antarctic ice streams to perturbations in heat fluxes occurring at decadal time scales.

BACKGROUND AND PURPOSE: Spinal cord atrophy is a common feature of MS. However, it is unknown which cord levels are most susceptible to atrophy. We performed whole cord imaging to identify the levels most susceptible to atrophy in patients with MS versus controls and also tested for differences among MS clinical phenotypes. MATERIALS AND METHODS: Thirty-five patients with MS (2 with CIS, 27 with RRMS, 2 with SPMS, and 4 with PPMS phenotypes) and 27 healthy controls underwent whole cord 3T MR imaging. The spinal cord contour was segmented and assigned to bins representing each C1 to T12 vertebral level. Volumes were normalized, and group comparisons were age-adjusted. RESULTS: There was a trend toward decreased spinal cord volume at the upper cervical levels in PPMS/SPMS versus controls. A trend toward increased spinal cord volume throughout the cervical and thoracic cord in RRMS/CIS versus controls reached statistical significance at the T10 vertebral level. A statistically significant decrease was found in spinal cord volume at the upper cervical levels in PPMS/SPMS versus RRMS/CIS. CONCLUSIONS: Opposing pathologic factors impact spinal cord volume measures in MS. Patients with PPMS demonstrated a trend toward upper cervical cord atrophy. However patients with RRMS showed a trend toward increased volume at the cervical and thoracic levels, which most likely reflects inflammation or edema-related cord expansion. With the disease causing both expansion and contraction of the cord, the specificity of spinal cord volume measures for neuroprotective therapeutic effect may be limited.

p-Cyanophenylalanine is an extremely useful fluorescence probe of protein structure that can be recombinantly and chemically incorporated into proteins. The probe has been used to study protein folding, protein-membrane interactions, protein-peptide interactions, and amyloid formation; however, the factors that control its fluorescence are not fully understood. Hydrogen bonding to the cyano group is known to play a major role in modulating the fluorescence quantum yield, but the role of potential side-chain quenchers has not yet been elucidated. A systematic study of the effects of different side chains on p-cyanophenylalanine fluorescence is reported. Tyr is found to have the largest effect followed by deprotonated His, Met, Cys, protonated His, Asn, Arg, and protonated Lys. Deprotonated amino groups are much more effective fluorescence quenchers than protonated amino groups. Free neutral imidazole and hydroxide ion are also effective quenchers of p-cyanophenylalanine fluorescence with Stern-Volmer constants of 39.8 and 22.1 M(-1), respectively. The quenching of p-cyanophenylalanine fluorescence by specific side chains is exploited in developing specific, high-sensitivity, fluorescence probes of helix formation. The approach is demonstrated with Ala-based peptides that contain a p-cyanophenylalanine-His or a p-cyanophenylalanine-Tyr pair located at positions i and i + 4. The p-cyanophenylalanine-His pair is most useful when the His side chain is deprotonated and is, thus, complementary to the Trp-His pair which is most sensitive when the His side chain is protonated.

Currently over 90 % of the thermally injured patients receive their care in an outpatient setting and this percentage is increasing. Though these patients do not require intensive therapies, they still require monitoring of their healing wounds, adequate pain control, appropriate assessment of their emotional healing and societal reintegration. Medical care in the USA is in a time of great change where we are being asked to reduce medical costs and expensive inpatient care, while maintaining and even improving the quality of the care we deliver. Burn centers, which have been successful in building great inpatient burn centers, will need spend time building and resourcing robust outpatient clinics and begin to monitoring outpatient patient outcomes.

International audience; Ice flow along land-terminating margins of the Greenland Ice Sheet (GIS) varies considerably in response to fluctuating inputs of surface meltwater to the bed of the ice sheet. Such inputs lubricate the ice–bed interface, transiently speeding up the flow of ice1, 2. Greater melting results in faster ice motion during summer, but slower motion over the subsequent winter, owing to the evolution of an efficient drainage system that enables water to drain from regions of the ice-sheet bed that have a high basal water pressure2, 3. However, the impact of hydrodynamic coupling on ice motion over decadal timescales remains poorly constrained. Here we show that annual ice motion across an 8,000-km2 land-terminating region of the west GIS margin, extending to 1,100 m above sea level, was 12% slower in 2007–14 compared with 1985–94, despite a 50% increase in surface meltwater production. Our findings suggest that, over these three decades, hydrodynamic coupling in this section of the ablation zone resulted in a net slowdown of ice motion (not a speed-up, as previously postulated1). Increases in meltwater production from projected climate warming may therefore further reduce the motion of land-terminating margins of the GIS. Our findings suggest that these sectors of the ice sheet are more resilient to the dynamic impacts of enhanced meltwater production than previously thought.

Most high-performance rocket engines employed on launch vehicles today use turbopumps to supply propellants to the combustion chamber at high volume flow rates and high pressures. While extensive experience exists in the rocket propulsion industry with these devices, relatively little experience exists in an academic setting. As such, Purdue University has embarked on an effort to design and built a high-performance turbopump capable of using a high-pressure gas generator to pump a storable oxidizer at a nominal flow rate of 170 GPM to a discharge pressure of 1400 psi. The overall configuration consists of a single-stage partial-admission axial impulse turbine driving a single-stage centrifugal pump and inducer assembly using a single shaft. The configuration will initially be tested using water and a high-flow hot-air source at Purdue’s Zucrow Laboratories. During development, extensive analysis and design attention was devoted to fluid dynamic simulation and cavitation suppression in the inducer and impeller, structural stress analysis and safety factors in all fixed and rotating components, overall system performance and power matching, case clearances, bearing load balancing, rotordynamic analysis, dynamic seal placement and leakage estimation, and manufacturing considerations. While the turbopump has yet to be tested, numerous lessons were learned during the development process. All this point, all critical design details have converged and the system is capable of meeting all of the performance and operational requirements. Hardware manufacturing is pending.

In Multiple Sclerosis (MS) patients, conventional magnetic resonance imaging (MRI) shows a pattern of white matter (WM) disruption but may also overlook some WM damage. Diffusion tensor MRI (DT-MRI) can provide important in-vivo information about fiber direction that is not provided by conventional MRI. The geometry of diffusion tensors can quantitatively characterize the local structure in tissues. The integration of both conventional MRI and DT-MRI measures together with connectivity-based regional assessment provide a better understanding of the nature and the location of WM abnormalities. Image processing and visualization techniques have been developed and applied to study conventional MRI and DT-MRI of MS patients. These include methods of: Image Segmentation for identifying the different areas of the brain as well as to discriminate normal from abnormal WM, Computerized Atlases, which include structural information obtained from a set of subjects, and Tractographies which can aid in the delineation of WM fiber tracts by tracking connected diffusion tensors. These new techniques hold out the promise of improving our understanding of WM architecture and its disruption in diseases such as MS. In the present study, we review the work that has been done in the development of these techniques and illustrate their applications.

Objective. Medical classification accuracy studies often yield continuous data based on predictive models for treatment outcomes. A popular method for evaluating the performance of diagnostic tests is the receiver operating characteristic (ROC) curve analysis. The main objective was to develop a global statistical hypothesis test for assessing the goodness-of-fit (GOF) for parametric ROC curves via the bootstrap.Design. A simple log (or logit) and a more flexible Box-Cox normality transformations were applied to untransformed or transformed data from two clinical studies to predict complications following percutaneous coronary interventions (PCIs) and for image-guided neurosurgical resection results predicted by tumor volume, respectively. We compared a non-parametric with a parametric binormal estimate of the underlying ROC curve. To construct such a GOF test, we used the non-parametric and parametric areas under the curve (AUCs) as the metrics, with a resulting p value reported.Results. In the interventional cardiology example, logit and Box-Cox transformations of the predictive probabilities led to satisfactory AUCs (AUC = 0.888; p = 0.78, and AUC = 0.888; p = 0.73, respectively), while in the brain tumor resection example, log and Box-Cox transformations of the tumor size also led to satisfactory AUCs (AUC = 0.898; p = 0.61, and AUC = 0.899; p = 0.42, respectively). In contrast, significant departures from GOF were observed without applying any transformation prior to assuming a binormal model (AUC = 0.766; p = 0.004, and AUC=0.831; p = 0.03), respectively.Conclusions. In both studies the p values suggested that transformations were important to consider before applying any binormal model to estimate the AUC. Our analyses also demonstrated and confirmed the predictive values of different classifiers for determining the interventional complications following PCIs and resection outcomes in image-guided neurosurgery.

Spherical harmonics (SH) were used to approximate the volume and three-dimensional geometry of multiple sclerosis (MS) lesions in deceased patients. The institutional ethical committee does not require its approval for studies involving pathologic specimens. Pathologic findings were used as the reference standard. In addition, lesion volume was measured with cylindrical approximation (CA). Volumetric comparisons of biases were based on summary statistics, Spearman correlation, Wilcoxon test, and two-way analysis of variance. Shape comparison metrics included mean distance and Dice similarity coefficient (DSC). Eight of 11 lesions had smaller biases with SH method (P < .001). Median biases with SH and CA did not differ significantly, as compared with pathologic findings (r = 1.00 vs 0.99, respectively). Variances of the biases were significantly smaller for SH (P =.04). Ranges of normalized distance and DSC were 0.1%–2.5% and 75%–96%, respectively. Mean DSC was significantly higher than 70% (P < .001). SH method provided unbiased lesion volume and added geometric information that may enable a better understanding of the pathogenesis and lesion evolution over time.

During neurosurgical procedures the objective of the neurosurgeon is to achieve the resection of as much diseased tissue as possible while achieving the preservation of healthy brain tissue. The restricted capacity of the conventional operating room to enable the surgeon to visualize critical healthy brain structures and tumor margin has lead, over the past decade, to the development of sophisticated intraoperative imaging techniques to enhance visualization. However, both rigid motion due to patient placement and nonrigid deformations occurring as a consequence of the surgical intervention disrupt the correspondence between preoperative data used to plan surgery and the intraoperative configuration of the patient's brain. Similar challenges are faced in other interventional therapies, such as in cryoablation of the liver, or biopsy of the prostate. We have developed algorithms to model the motion of key anatomical structures and system implementations that enable us to estimate the deformation of the critical anatomy from sequences of volumetric images and to prepare updated fused visualizations of preoperative and intraoperative images at a rate compatible with surgical decision making. This paper reviews the experience at Brigham and Women's Hospital through the process of developing and applying novel algorithms for capturing intraoperative deformations in support of image guided therapy.

A new approach to approximate the 3-D shape of multiple sclerosis (MS) lesions and to calculate their volumes is presented. The suggested method utilizes sets of MS lesion contours taken from segmented MR images and approximates their 3-D surfaces by spherical harmonics. This method was applied to obtain 3-D reconstructions of in vivo and simulated MS lesions and to calculate their volumes. The results show good geometrical approximations of the original MS lesions' 3-D shapes and good consistency in volume estimation independent of the size of the lesions. The average volume estimation error was smaller than the commonly used technique of slice stacking (15.5 +/- 13.4% and 13.1 +/- 10.1% vs. 25.0 +/- 17.0%). The method presented here offers a tool for analyzing the geometrical characteristics of MS lesions in 3-D as well as their volumes. The geometrical information may potentially serve as an additional clinical index for monitoring the disease.

Nicardipine is the first intravenously administered dihydropyridine calcium channel blocker. Its primary physiologic actions include vasodilatation with limited effects on the inotropic and dromotropic function of the myocardium. Although it was used in the past as an agent for controlled hypotension during orthopedic surgery in adults and children, we are unaware of reports concerning its use for controlled hypotension during maxillofacial surgery. We present our experience with nicardipine as an agent for controlled hypotension during orthognathic surgery in nine adolescents ranging in age from 11 to 16 years and in weight from 39 to 61 kg. Following induction of general anesthesia, nicardipine was started at 5 micrograms/kg per minute. The target mean arterial pressure of 50 to 65 mmHg was reached in 2 to 12 minutes (mean 5.5 minutes). Intraoperative infusion requirements to maintain the target mean arterial pressure varied from 1 to 7 micrograms/kg per minute (mean 3.6 micrograms/kg per minute). No adverse effects related to nicardipine were noted. Our preliminary experience suggests the efficacy of nicardipine for controlled hypotension in adolescents during orthognathic surgery. Future studies are required to determine its advantages and disadvantages over more commonly used agents such as sodium nitroprusside or adrenergic antagonists.

Dynamic and thermodynamic regimes of ice shelves experiencing weak (inline image1 m year−1) to strong (~10 m year−1) basal melting in cold (bottom temperature close to the in situ freezing point) and warm oceans (bottom temperature more than half of a degree warmer than the in situ freezing point) are investigated using a 1-D coupled ice/ocean model complemented with a newly derived analytic expression for the steady state temperature distribution in ice shelves. This expression suggests the existence of a basal thermal boundary layer with thickness inversely proportional to the basal melt rate. Model simulations show that ice shelves afloat in warm ocean waters have significantly colder internal ice temperatures than those that float in cold waters. Our results indicate that in steady states, the mass balance of ice shelves experiencing strong and weak melting is controlled by different processes: in ice shelves with strong melting, it is a balance between ice advection and basal melting, and in ice shelves with weak melting, it is a balance between ice advection and deformation. Sensitivity simulations show that ice shelves in cold and warm oceans respond differently to increase of the ocean heat content. Ice shelves in cold waters are more sensitive to warming of the ocean bottom waters, while ice shelves in warm waters are more sensitive to shallowing of the depth of the thermocline.

Severe injury remains a leading cause of death and morbidity in patients under 40, with the number of annual trauma-related deaths approaching 160,000 in the United States. Patients who survive the initial trauma and post-traumatic resuscitation are at risk for immune dysregulation, which contributes to late mortality and accounts for approximately 20% of deaths after traumatic injury. This post-traumatic immunosuppressed state has been attributed to over-expression of anti-inflammatory mediators in an effort to restore host homeostasis. We measured a panel of monocyte markers and cytokines in 50 severely injured trauma patients for 3 days following admission. We made the novel observation that the subpopulation of monocytes expressing high levels of CD14 and CD16 was expanded in the majority of patients. These cells also expressed CD163 consistent with differentiation into alternatively activated macrophages with potential regulatory or wound-healing activity. We examined factors in trauma plasma that may contribute to the generation and activation of these cells. The percentage of CD14(high)CD16(+) monocytes after trauma correlated strongly with plasma C-reactive protein (CRP) transforming growth factor-β (TGF-β), and macrophage colony-stimulating factor (M-CSF) levels. We demonstrate a role for TGF-β and M-CSF, but not CRP in generating these cells using monocytes from healthy volunteers incubated with plasma from trauma patients. CD16 is a receptor for CRP and IgG, and we showed that monocytes differentiated to the CD14(high)CD16(+) phenotype produced anti-inflammatory cytokines in response to acute phase concentrations of CRP. The role of these cells in immunosuppression following trauma is an area of ongoing investigation.

[1] Antarctic ice shelves interact closely with the ocean cavities beneath them, with ice shelf geometry influencing ocean cavity circulation, and heat from the ocean driving changes in the ice shelves, as well as the grounded ice streams that feed them. We present a new coupled model of an ice stream-ice shelf-ocean system that is used to study this interaction. The model is capable of representing a moving grounding line and dynamically responding ocean circulation within the ice shelf cavity. Idealized experiments designed to investigate the response of the coupled system to instantaneous increases in ocean temperature show ice-ocean system responses on multiple timescales. Melt rates and ice shelf basal slopes near the grounding line adjust in 1–2 years, and downstream advection of the resulting ice shelf thinning takes place on decadal timescales. Retreat of the grounding line and adjustment of grounded ice takes place on a much longer timescale, and the system takes several centuries to reach a new steady state. During this slow retreat, and in the absence of either an upward-or downward-sloping bed or long-term trends in ocean heat content, the ice shelf and melt rates maintain a characteristic pattern relative to the grounding line.

Ice-shelf basal melting is tightly coupled to ice-shelf morphology. Ice shelves, in turn, are coupled to grounded ice via their influence on compressive stress at the grounding line (‘ice-shelf buttressing’). Here, we examine this interaction using a local parameterization that relates the basal melt rate to the ice-shelf thickness gradient. This formulation permits a closed-form solution for a steady-state ice tongue. Time-dependent numerical simulations reveal the spatial and temporal evolution of ice-shelf/ice-stream systems in response to changes in ocean temperature, and the influence of morphology-dependent melting on grounding-line retreat. We find that a rapid (

Predictions of marine ice-sheet behaviour require models that are able to robustly simulate grounding line migration. We present results of an intercomparison exercise for marine ice-sheet models. Verification is effected by comparison with approximate analytical solutions for flux across the grounding line using simplified geometrical configurations (no lateral variations, no effects of lateral buttressing). Unique steady state grounding line positions exist for ice sheets on a downward sloping bed, while hysteresis occurs across an overdeepened bed, and stable steady state grounding line positions only occur on the downward-sloping sections. Models based on the shallow ice approximation, which does not resolve extensional stresses, do not reproduce the approximate analytical results unless appropriate parameterizations for ice flux are imposed at the grounding line. For extensional-stress resolving "shelfy stream" models, differences between model results were mainly due to the choice of spatial discretization. Moving grid methods were found to be the most accurate at capturing grounding line evolution, since they track the grounding line explicitly. Adaptive mesh refinement can further improve accuracy, including fixed grid models that generally perform poorly at coarse resolution. Fixed grid models, with nested grid representations of the grounding line, are able to generate accurate steady state positions, but can be inaccurate over transients. Only one full-Stokes model was included in the intercomparison, and consequently the accuracy of shelfy stream models as approximations of full-Stokes models remains to be determined in detail, especially during transients. © 2012 Author(s)., SCOPUS: ar.j, info:eu-repo/semantics/published

To determine the interrelationships between MRI-defined lesion and atrophy measures of spinal cord involvement and brain involvement and their relationships to disability in a small cohort of patients with multiple sclerosis (MS).Although it is known that cervical spinal cord atrophy correlates with disability in MS, it is unknown whether it is the most important determinant when compared to other regions of the central nervous system (CNS). Furthermore, it is not clear to what extent brain and cord lesions and atrophy are related.3T MRI of the whole brain and whole spinal cord was obtained in 21 patients with MS, including 18 with relapsing-remitting, one with secondary progressive, one with primary progressive, and one with a clinically isolated syndrome. Brain global gray and white matter volumes were segmented with Statistical Parametric Mapping 8. Spinal cord contour volume was segmented in whole by a semi-automated method with bins assigned to either the cervical or thoracic regions. All CNS volumes were normalized by the intracranial volume. Brain and cord T2 hyperintense lesions were segmented using a semi-automated edge finding tool.Among all MRI measures, only upper cervical spinal cord volume significantly correlated with Expanded Disability Status Scale score (r =-.515, P = .020). The brain cord relationships between whole or regional spinal cord volume or lesions and gray matter, white matter, or whole brain volume or whole brain lesions were generally weak and all nonsignificant.In this preliminary study of mildly disabled, treated MS patients, cervical spinal cord atrophy most strongly correlates with physical disability in MS when accounting for a wide range of other CNS measures of lesions and atrophy, including thoracic or whole spinal cord volume, and cerebral gray, white or whole brain volume. The weak relationship between spinal cord and brain lesions and atrophy may suggest that they progress rather independently in patients with MS.

An approximation to the first-order momentum balance with consistent boundary conditions is derived using variational methods. Longitudinal and lateral stresses are treated as depth-independent, but vertical velocity gradients are accounted for both in the nonlinear viscosity and in the treatment of basal stress, allowing for flow over a frozen bed. A numerical scheme is presented that is significantly less computationally expensive than that of a fully three-dimensional (3-D) solver. The numerical solver is subjected to the ISMIP-HOM experiments and experiments involving nonlinear sliding laws, and results are compared with those of 3-D models. The agreement with first-order surface velocities is favorable down to length scales of 10 km for flow over a flat bed with periodic basal traction, and ∼40 km for flow over periodic basal topography.

Hybrid models, or depth-integrated flow models that include the effect of both longitudinal stresses and vertical shearing, are becoming more prevalent in dynamical ice modeling. Under a wide range of conditions they closely approximate the well-known First Order stress balance, yet are of computationally lower dimension, and thus require less intensive resources. Concomitant with the development and use of these models is the need to perform inversions of observed data. Here, an inverse control method is extended to use a hybrid flow model as a forward model. We derive an adjoint of a hybrid model and use it for inversion of ice-stream basal traction from observed surface velocities. A novel aspect of the adjoint derivation is a retention of non-linearities in Glen's flow law. Experiments show that in some cases, including those nonlinearities is advantageous in minimization of the cost function, yielding a more efficient inversion procedure.

Approved symptomatic therapies for Alzheimer's disease (AD) provide modest relief. In the future, it is likely that symptomatic treatments will be utilized with AD modifying therapies, the development of which are currently a primary focus of research. The nicotinic α7 receptor agonist may be an attractive drug candidate to potentially improve cognition in Alzheimer's disease patients either as a stand-alone therapy or in combination with other symptomatic treatments. EVP-6124 is a novel, potent, and selective α7 nicotinic receptor agonist. EVP-6124 has an excellent brain to plasma exposure ratio and has shown excellent efficacy and potency in a number of animal models of cognition. Four clinical studies in >125 healthy normal human subjects have been completed with EVP-6124, including a single-ascending-dose study, a 14-day multiple-ascending-dose study, a 21-day multiple-dose study, and a single-dose relative bioavailability, food, and gender effect study. EVP-6124 exhibited linear kinetics over the range of 1 to 180 mg and demonstrated a half-life suitable for once daily dosing. EVP-6124 appears to be safe and well tolerated for up to 21 days as measured by adverse events, vital signs, continuous cardiac monitoring, physical examination, and clinical laboratory evaluations. In addition, in normal volunteers, EVP-6124 demonstrated pro-cognitive effects (CogState testing) in various cognitive domains including executive function. These data suggest that EVP-6124 administered to AD subjects on stable cholinesterase inhibitor therapies may have potential benefit and that further study in this patient population is indicated. Larger phase II studies are currently being initiated in both Alzheimer's disease and schizophrenia.

Background Glutamate has been proposed as a transmitter in the peripheral taste system in addition to its well-documented role as an umami taste stimulus. Evidence for a role as a transmitter includes the presence of ionotropic glutamate receptors in nerve fibers and taste cells, as well as the expression of the glutamate transporter GLAST in Type I taste cells. However, the source and targets of glutamate in lingual tissue are unclear. In the present study, we used molecular, physiological and immunohistochemical methods to investigate the origin of glutamate as well as the targeted receptors in taste buds. Results Using molecular and immunohistochemical techniques, we show that the vesicular transporters for glutamate, VGLUT 1 and 2, but not VGLUT3, are expressed in the nerve fibers surrounding taste buds but likely not in taste cells themselves. Further, we show that P2X2, a specific marker for gustatory but not trigeminal fibers, co-localizes with VGLUT2, suggesting the VGLUT-expressing nerve fibers are of gustatory origin. Calcium imaging indicates that GAD67-GFP Type III taste cells, but not T1R3-GFP Type II cells, respond to glutamate at concentrations expected for a glutamate transmitter, and further, that these responses are partially blocked by NBQX, a specific AMPA/Kainate receptor antagonist. RT-PCR and immunohistochemistry confirm the presence of the Kainate receptor GluR7 in Type III taste cells, suggesting it may be a target of glutamate released from gustatory nerve fibers. Conclusions Taken together, the results suggest that glutamate may be released from gustatory nerve fibers using a vesicular mechanism to modulate Type III taste cells via GluR7.

[1] Understanding the dynamics of marine ice sheets is integral to studying the evolution of the Antarctic ice sheet in both the short and long terms. An important component of the dynamics, grounding line migration, has proved difficult to represent in numerical models, and most successful attempts have made use of techniques that are only readily applicable to flow line models. However, to capture the stress transmission involved in another important component, the buttressing of a marine ice sheet by its ice shelf, the transverse direction must also be resolved. We introduce a model that solves the time-dependent shelfy stream equations and makes use of mesh adaption techniques to overcome the difficulties typically associated with the numerics of grounding line migration. We compare the model output with a recent benchmark for flow line models and show that our model yields an accurate solution while using far less resources than would be required without mesh adaption. We also show that the mesh adapting techniques extend to two horizontal dimensions. Experiments are carried out to determine how both ice shelf buttressing and ice rises affect the marine instability predicted for an ice sheet on a foredeepened bed. We find that buttressing is not always sufficient to stabilize such a sheet but collapse of the grounded portion is still greatly delayed. We also find that the effect of an ice rise is similar to that of narrowing the ice shelf.

MRI at 3 T has increased sensitivity in detecting overt multiple sclerosis (MS) brain lesions; a growing body of data suggests clinically relevant damage occurs in the normal-appearing white matter (NAWM). We tested a novel pulse sequence to determine whether 3 T MRI spin–spin relaxometry detected damage in NAWM of MS patients (n = 13) vs. age-matched normal controls [(NL) (n = 11)]. Baseline characteristics of the MS group were: age (mean ± SD) 42.5 ± 5.4 (range 33–51 years), disease duration 9.0 ± 6.4 (range 1–22 years), Expanded Disability Status Scale score 2.5 ± 1.7 (range 1–6.5). Brain MRI measures, obtained at 3 T, included global and regional NAWM transverse relaxation rate [R2 (= 1/T2)], derived from 3D fast spin-echo T2 prepared images, and global white matter volume fraction derived from SPGR images. The regional NAWM areas investigated were the frontal lobe, parietal lobe, and the genu and splenium of the corpus callosum. Mean NAWM R2 was lower (indicating T2 prolongation) in MS than NL in the whole brain (p = 0.00047), frontal NAWM (p = 0.00015), parietal NAWM (p = 0.0069) and callosal genu (p = 0.0019). Similarly, R2 histogram peak position was lower in NAWM in MS than NL in the whole brain (p = 0.019). However, the normalized WM volume fractions were similar in both MS and NL (p > 0.1). This pilot study suggests that a novel 3D fast spin-echo pulse sequence at 3 T, used to derive R2 relaxation maps, can detect tissue damage in the global and regional cerebral NAWM of MS patients that is missed by conventional lesion and atrophy measures. Such findings may represent demyelination, inflammation, glial proliferation and axonal loss.

OR Concepts Applied has designed and implemented a human factors test bed to evaluate adaptive autonomy schemes and a range of levels of autonomy for UAV supervisory control. The test bed includes a high fidelity simulation that interfaces with a mission control element (MCE) that supports multi-vehicle control. The MCE uses OPUS mission planning tools to provide the operator with optimization and analysis decision aids. SA Technologies, Inc. was instrumental in helping to create user interface elements to help maintain high levels of situation awareness even when the level of automation is increased. The test bed provides a variety of tools for researchers to create scenarios, alter adaptive schemas, and collect experimental data.

Multiple sclerosis (MS), a demyelinating disease, occurs principally in the white matter (WM) of the central nervous system. Conventional magnetic resonance imaging (MRI) is sensitive to some, but not all, brain changes associated with MS. Diffusion-weighted imaging (DWI) provides information about water diffusion in tissue and diffusion tensor MRI (DT-MRI) about fiber direction, allowing for the identification of WM abnormalities that are not apparent on conventional MRI images. These techniques can quantitatively characterize the local microstructure of tissues. MS-associated disease processes lead to regions characterized by an increased amount of water diffusion and a decrease in the anisotropy of diffusion direction. These changes have been found to produce different patterns in MS patients presenting different courses of the disease. Changes in water diffusion may allow examination of the type, appearance, enhancement, and location of lesions not readily visible by other means. Ongoing studies of MS are integrating conventional MRI and DT-MRI measures with connectivity-based regional assessment, aiming to provide a better understanding of the nature and the location of WM lesions. This integration and the development of novel image-processing and visualization techniques may improve the understanding of WM architecture and its disruption in MS. This article presents a brief history of DWI, its basic principles and applications in the study of MS, a review of the properties and applications of DT-MRI, and their use in the study of MS. In addition, this article illustrates the methodology for the analysis of DT-MRI in ongoing studies of MS.

An architecture tor testing and evaluating different methods for adaptive levels of autonomy was devised. We defined multiple Levels of Autonomy (LOA) for each of four operator tasks: allocation, route planning, imagery analysis, and weapon control. To demonstrate the architecture and LOA implementation, we designed a prototype Multi-UAV Control Station Emulator research test bed, by building on existing ORCA-developed software components. ORCA's extensive internal IR&D over several years has produced state-of-the-art automated mission planning tools that allow fully autonomous execution of operator tasks. Experience with operators through the J-UCAS effort and other programs gives us first-hand knowledge of the tools and decision aids operators need when building and assessing mission plans, which support manual mission planning. With this experience, we implemented the two autonomy extremes: manual and fully autonomous and we defined and implemented intermediate levels of autonomy (requires using characteristics of both manual and autonomous task execution for the four operator tasks noted above.

In any medical domain, it is common to have more than one test (classifier) to diagnose a disease. In image analysis, for example, there is often more than one reader or more than one algorithm applied to a certain data set. Combining of classifiers is often helpful, but determining the way in which classifiers should be combined is not trivial. Standard strategies are based on learning classifier combination functions from data. We describe a simple strategy to combine results from classifiers that have not been applied to a common data set, and therefore can not undergo this type of joint training. The strategy, which assumes conditional independence of classifiers, is based on the calculation of a combined Receiver Operating Characteristic (ROC) curve, using maximum likelihood analysis to determine a combination rule for each ROC operating point. We offer some insights into the use of ROC analysis in the field of medical imaging.

Rationale and objectives Surgical planning now routinely uses both two-dimensional (2D) and three-dimensional (3D) models that integrate data from multiple imaging modalities, each highlighting one or more aspects of morphology or function. We performed a preliminary evaluation of the use of spherical harmonics (SH) in approximating the 3D shape and estimating the volume of brain tumors of varying characteristics. Materials and methods Magnetic resonance (MR) images from five patients with brain tumors were selected randomly from our MR-guided neurosurgical practice. Standardized mean square reconstruction errors (SMSRE) by tumor volume were measured. Validation metrics for comparing performances of the SH method against segmented contours (SC) were the dice similarity coefficient (DSC) and standardized Euclidean distance (SED) measure. Results Tumor volume range was 22413–85189 mm3, and range of number of vertices in triangulated models was 3674–6544. At SH approximations with degree of at least 30, SMSRE were within 1.66 × 10–5 mm−1. Summary measures yielded a DSC range of 0.89–0.99 (pooled median, 0.97 and significantly >0.7; P Conclusion 3D shapes of tumors may be approximated by using SH for neurosurgical applications.

To suggest a quantitative method for assessing the temporal changes in the geometry of individual multiple sclerosis (MS) lesions in follow-up studies of MS patients.Computer simulated and in vivo magnetic resonance (MR) imaged MS lesions were studied. Ten in vivo MS lesions were identified from sets of axial MR images acquired from a patient scanned consecutively for 24 times during a one-year period. Each of the lesions was segmented and its three-dimensional surface approximated using spherical harmonics (SH). From the obtained SH polynomial coefficients, indices of shape were defined, and analysis of the temporal changes in each lesion's geometry throughout the year was performed by determining the mean discrete total variation of the shape indices.The results demonstrate that most of the studied lesions undergo notable geometrical changes with time. These changes are not necessarily associated with similar changes in size/volume. Furthermore, it was found that indices corresponding to changes in lesion shape could be 1.4 to 8.0 times higher than those corresponding to changes in the lesion size/volume.Quantitative three-dimensional shape analysis can serve as a new tool for monitoring MS lesion activity and study patterns of MS lesion evolution over time.

In the longitudinal study of multiple sclerosis (MS) lesions, varying position of the patient inside the MRI scanner is one of the major sources of assessment errors. We propose to use analytical indices that are invariant to spatial orientation to describe the lesions, rather than focus on patient repositioning or image realignment. Studies were made on simulated lesions systematically rotated, from in vitro MS lesions scanned on different days, and from in vivo MS lesions from a patient that was scanned five times the same day with short intervals of time between scans. Each of the lesions' 3D surfaces was approximated using spherical harmonics, from which indices that are invariant to space rotation were derived. From these indices, an accurate and highly reproducible volume estimate can be derived, which is superior to the common approach of 2D slice stacking. The results indicate that the suggested approach is useful in reducing part of the errors that affect the analysis of changes of MS lesions during follow-up studies. In conclusion, our proposed method circumvents the need for precise patient repositioning and can be advantageous in MRI longitudinal studies of MS patients.

In the present study an automatic algorithm for detection and contouring of multiple sclerosis (MS) lesions in brain magnetic resonance (MR) images is introduced. This algorithm automatically detects MS lesions in axial proton density, T2-weighted, gadolinium enhanced, and fast fluid attenuated inversion recovery (FLAIR) brain MR images. Automated detection consists of three main stages: (1) detection and contouring of all hyperintense signal regions within the image; (2) partial elimination of false positive segments (defined herein as artifacts) by size, shape index, and anatomical location; (3) the use of an artificial neural paradigm (Back-Propagation) for final removal of artifacts by differentiating them from true MS lesions. The algorithm was applied to 45 images acquired from 14 MS patients. The algorithm’s sensitivity was 0.87 and the specificity 0.96. In 34 images, 100% of the lesions were detected. The algorithm potentially may serve as a useful preprocessing tool for quantitative MS monitoring via magnetic resonance imaging.

A series of 178 immediate reconstructions with regional or distant tissue for repair of oropharyngeal defects caused by treatment of head and neck cancer was reviewed to determine whether reconstruction with free flaps was more or less expensive than reconstruction with regional myocutaneous flaps. In this series, three types of flaps were used: the radial forearm free flap (n = 89), the rectus abdominis free flap (n = 56), and the pectoralis major myocutaneous flap (n = 33). Resource costs were determined by adding all costs to the institution of providing each service studied using salaried employees (including physicians). The two free-flap groups were combined to compare free flaps with the pectoralis major myocutaneous flap, a regional myocutaneous flap. Failure rates in the two groups were similar (3.0 percent for pectoralis major myocutaneous flap, 3.4 percent for free flaps). The mean costs of surgery were slightly higher for the free flaps, but the subsequent hospital stay costs were lower. Therefore, the total mean resource cost for the free-flap group ($28,460) was lower than the cost for the myocutaneous-flap group ($40,992). The pectoralis major myocutaneous flap may have been selected for more patients with advanced disease and systemic medical problems, contributing to longer hospitalization and added cost. Nevertheless, this study suggests that free flaps are not more expensive than other methods and may provide cost savings for selected patients.

Background Voxel based morphometry (VBM) is an automated tool used to assess the topography and magnitude of cerebral atrophy from MRI scans. However, VBM output is highly dependent on the input provided by registration and segmentation algorithms. Diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) is a new tool which has recently been developed to improve registration in healthy volunteers (HV) and neurodegenerative diseases. This has not yet been applied to multiple sclerosis (MS). Objective To assess regional gray matter (GM) and white matter (WM) atrophy using VBM combined with DARTEL in MS patients. Methods Using a 3T MRI scanner, fluid-attenuated inversion-recovery (FLAIR) and 3D spoiled gradient recalled (SPGR) scans were acquired from 26 relapsing remitting (RR) MS patients [age (mean ± SD) 39.2 ± 9.4 years, disease duration 8.5 ± 5.9 years, Expanded Disability Status Scale (EDSS) score 1.2 ± 0.9, FLAIR lesion volume (FLV) 15.0 ± 14.7 mL] and 28 sex- and age-matched HV. MS lesions on SPGR and FLAIR images were traced using a semi-automated thresholding tool. VBM was performed using DARTEL with statistical parametric mapping (SPM8) software from SPGR images. An analysis of covariance was used to assess differences in GM and WM volume between MS patients and HV. Age, gender, and intracranial volume were included as covariates. Results Compared with HV, MS patients showed significant GM atrophy in the bilateral thalami, bilateral caudate, and right putamen. Furthermore, WM atrophy was found in the brainstem, corpus callosum, fornix, and bilateral temporal and occipital lobes. FLV significantly correlated with GM atrophy in the thalami and with WM atrophy in the brainstem, temporal lobes, and corpus callosum. Conclusions VBM-DARTEL reveals widespread WM and GM cerebral atrophy affecting many areas of the brain, which is associated with overt lesions in MS patients. This pilot study suggests that VBM-DARTEL is a promising tool to derive meaningful disease specific information in MS. Acknowledgements This work was supported by research grants from the National Institutes of Health ( NIH R01 NS055083-01 ) and the National Multiple Sclerosis Society ( RG3705A1 , RG3798A2 ).

Objective To assess whole and regional spinal cord atrophy in patients with multiple sclerosis (MS) using 3T MRI. Background Spinal cord damage is common in MS and provides a unique and clinically relevant means to monitor disease progression and therapeutic effects. Whereas regional spinal cord atrophy has been studied extensively in MS, whole spinal cord atrophy has not been previously assessed. Design/Methods Whole spinal cord 3 mm thick T2-weighted axial fast spin-echo MRI images were obtained at 3T on 34 patients with MS [26 women and 8 men; 26 relapsing–remitting, 2 clinically isolated syndrome, 4 secondary progressive, 2 primary progressive; Expanded Disability Status Scale (EDSS) (mean ± SD) 1.95 ± 1.72, range 0–6.5] and 15 age-matched normal controls [11 women and 4 men]. The global and regional (cervical, C2–3, and thoracic) cord volumes were determined using a semi-automated tool and were normalized by the segment length and intracranial volume. Spinal cord lesions were also determined using a semi-automated edge finding tool. Results Whole cord, C2–3, cervical, and thoracic volumes were lower in progressive vs. relapsing patients or normal controls (all p Conclusions The established method of estimating spinal cord atrophy, C2–3 cross-sectional volume, provides a useful surrogate of overall global or regional spinal cord atrophy. Spinal cord atrophy is most common in progressive forms of MS and is related to neurologic disability. Support This study was supported by grants from the National Institutes of Health ( 1R01NS055083-01 ) and the National Multiple Sclerosis Society ( RG3705A1 ; RG3798A2 ).