Using MDEFT MRI Sequences to Target the GPi in DBS Surgery.

OBJECTIVE Recent advances in different MRI sequences have enabled direct visualization and targeting of the Globus pallidus internus (GPi) for DBS surgery. Modified Driven Equilibrium Fourier Transform (MDEFT) MRI sequences provide high spatial resolution and an excellent contrast of the basal ganglia with low distortion. In this study, we investigate if MDEFT sequences yield accurate and reliable targeting of the GPi and compare direct targeting based on MDEFT sequences with atlas-based targeting. METHODS 13 consecutive patients considered for bilateral GPi-DBS for dystonia or PD were included in this study. Preoperative targeting of the GPi was performed visually based on MDEFT sequences as well as by using standard atlas coordinates. Postoperative CT imaging was performed to calculate the location of the implanted leads as well as the active electrode(s). The coordinates of both visual and atlas based targets were compared. The stereotactic coordinates of the lead and active electrode(s) were calculated and projected on the segmented GPi. RESULTS On MDEFT sequences the GPi was well demarcated in most patients. Compared to atlas-based planning the mean target coordinates were located significantly more posterior. Subgroup analysis showed a significant difference in the lateral coordinate between dystonia (LAT = 19.33 ± 0.90) and PD patients (LAT = 20.67 ± 1.69). Projected on the segmented preoperative GPi the active contacts of the DBS electrode in both dystonia and PD patients were located in the inferior and posterior part of the structure corresponding to the motor part of the GPi. CONCLUSIONS MDEFT MRI sequences provide high spatial resolution and an excellent contrast enabling precise identification and direct visual targeting of the GPi. Compared to atlas-based targeting, it resulted in a significantly different mean location of our target. Furthermore, we observed a significant variability of the target among the PD and dystonia subpopulation suggesting accurate targeting for each individual patient.

New Algorithms for M-Estimation of Multivariate Scatter and Location

We present new algorithms for M-estimators of multivariate scatter and location and for symmetrized M-estimators of multivariate scatter. The new algorithms are considerably faster than currently used fixed-point and related algorithms. The main idea is to utilize a second order Taylor expansion of the target functional and to devise a partial Newton-Raphson procedure. In connection with symmetrized M-estimators we work with incomplete U-statistics to accelerate our procedures initially.

Distributed collaborative processing in wireless sensor networks with application to target localization and beamforming

Abstract The proliferation of wireless sensor networks and the variety of envisioned applications associated with them has motivated the development of distributed algorithms for collaborative processing over networked systems. One of the applications that has attracted the attention of the researchers is that of target localization where the nodes of the network try to estimate the position of an unknown target that lies within its coverage area. Particularly challenging is the problem of estimating the target’s position when we use received signal strength indicator (RSSI) due to the nonlinear relationship between the measured signal and the true position of the target. Many of the existing approaches suffer either from high computational complexity (e.g., particle filters) or lack of accuracy. Further, many of the proposed solutions are centralized which make their application to a sensor network questionable. Depending on the application at hand and, from a practical perspective it could be convenient to find a balance between localization accuracy and complexity. Into this direction we approach the maximum likelihood location estimation problem by solving a suboptimal (and more tractable) problem. One of the main advantages of the proposed scheme is that it allows for a decentralized implementation using distributed processing tools (e.g., consensus and convex optimization) and therefore, it is very suitable to be implemented in real sensor networks. If further accuracy is needed an additional refinement step could be performed around the found solution. Under the assumption of independent noise among the nodes such local search can be done in a fully distributed way using a distributed version of the Gauss-Newton method based on consensus. Regardless of the underlying application or function of the sensor network it is al¬ways necessary to have a mechanism for data reporting. While some approaches use a special kind of nodes (called sink nodes) for data harvesting and forwarding to the outside world, there are however some scenarios where such an approach is impractical or even impossible to deploy. Further, such sink nodes become a bottleneck in terms of traffic flow and power consumption. To overcome these issues instead of using sink nodes for data reporting one could use collaborative beamforming techniques to forward directly the generated data to a base station or gateway to the outside world. In a dis-tributed environment like a sensor network nodes cooperate in order to form a virtual antenna array that can exploit the benefits of multi-antenna communications. In col-laborative beamforming nodes synchronize their phases in order to add constructively at the receiver. Some of the inconveniences associated with collaborative beamforming techniques is that there is no control over the radiation pattern since it is treated as a random quantity. This may cause interference to other coexisting systems and fast bat-tery depletion at the nodes. Since energy-efficiency is a major design issue we consider the development of a distributed collaborative beamforming scheme that maximizes the network lifetime while meeting some quality of service (QoS) requirement at the re¬ceiver side. Using local information about battery status and channel conditions we find distributed algorithms that converge to the optimal centralized beamformer. While in the first part we consider only battery depletion due to communications beamforming, we extend the model to account for more realistic scenarios by the introduction of an additional random energy consumption. It is shown how the new problem generalizes the original one and under which conditions it is easily solvable. By formulating the problem under the energy-efficiency perspective the network’s lifetime is significantly improved. Resumen La proliferación de las redes inalámbricas de sensores junto con la gran variedad de posi¬bles aplicaciones relacionadas, han motivado el desarrollo de herramientas y algoritmos necesarios para el procesado cooperativo en sistemas distribuidos. Una de las aplicaciones que suscitado mayor interés entre la comunidad científica es la de localization, donde el conjunto de nodos de la red intenta estimar la posición de un blanco localizado dentro de su área de cobertura. El problema de la localization es especialmente desafiante cuando se usan niveles de energía de la seal recibida (RSSI por sus siglas en inglés) como medida para la localization. El principal inconveniente reside en el hecho que el nivel de señal recibida no sigue una relación lineal con la posición del blanco. Muchas de las soluciones actuales al problema de localization usando RSSI se basan en complejos esquemas centralizados como filtros de partículas, mientas que en otras se basan en esquemas mucho más simples pero con menor precisión. Además, en muchos casos las estrategias son centralizadas lo que resulta poco prácticos para su implementación en redes de sensores. Desde un punto de vista práctico y de implementation, es conveniente, para ciertos escenarios y aplicaciones, el desarrollo de alternativas que ofrezcan un compromiso entre complejidad y precisión. En esta línea, en lugar de abordar directamente el problema de la estimación de la posición del blanco bajo el criterio de máxima verosimilitud, proponemos usar una formulación subóptima del problema más manejable analíticamente y que ofrece la ventaja de permitir en¬contrar la solución al problema de localization de una forma totalmente distribuida, convirtiéndola así en una solución atractiva dentro del contexto de redes inalámbricas de sensores. Para ello, se usan herramientas de procesado distribuido como los algorit¬mos de consenso y de optimización convexa en sistemas distribuidos. Para aplicaciones donde se requiera de un mayor grado de precisión se propone una estrategia que con¬siste en la optimización local de la función de verosimilitud entorno a la estimación inicialmente obtenida. Esta optimización se puede realizar de forma descentralizada usando una versión basada en consenso del método de Gauss-Newton siempre y cuando asumamos independencia de los ruidos de medida en los diferentes nodos. Independientemente de la aplicación subyacente de la red de sensores, es necesario tener un mecanismo que permita recopilar los datos provenientes de la red de sensores. Una forma de hacerlo es mediante el uso de uno o varios nodos especiales, llamados nodos “sumidero”, (sink en inglés) que actúen como centros recolectores de información y que estarán equipados con hardware adicional que les permita la interacción con el exterior de la red. La principal desventaja de esta estrategia es que dichos nodos se convierten en cuellos de botella en cuanto a tráfico y capacidad de cálculo. Como alter¬nativa se pueden usar técnicas cooperativas de conformación de haz (beamforming en inglés) de manera que el conjunto de la red puede verse como un único sistema virtual de múltiples antenas y, por tanto, que exploten los beneficios que ofrecen las comu¬nicaciones con múltiples antenas. Para ello, los distintos nodos de la red sincronizan sus transmisiones de manera que se produce una interferencia constructiva en el recep¬tor. No obstante, las actuales técnicas se basan en resultados promedios y asintóticos, cuando el número de nodos es muy grande. Para una configuración específica se pierde el control sobre el diagrama de radiación causando posibles interferencias sobre sis¬temas coexistentes o gastando más potencia de la requerida. La eficiencia energética es una cuestión capital en las redes inalámbricas de sensores ya que los nodos están equipados con baterías. Es por tanto muy importante preservar la batería evitando cambios innecesarios y el consecuente aumento de costes. Bajo estas consideraciones, se propone un esquema de conformación de haz que maximice el tiempo de vida útil de la red, entendiendo como tal el máximo tiempo que la red puede estar operativa garantizando unos requisitos de calidad de servicio (QoS por sus siglas en inglés) que permitan una decodificación fiable de la señal recibida en la estación base. Se proponen además algoritmos distribuidos que convergen a la solución centralizada. Inicialmente se considera que la única causa de consumo energético se debe a las comunicaciones con la estación base. Este modelo de consumo energético es modificado para tener en cuenta otras formas de consumo de energía derivadas de procesos inherentes al funcionamiento de la red como la adquisición y procesado de datos, las comunicaciones locales entre nodos, etc. Dicho consumo adicional de energía se modela como una variable aleatoria en cada nodo. Se cambia por tanto, a un escenario probabilístico que generaliza el caso determinista y se proporcionan condiciones bajo las cuales el problema se puede resolver de forma eficiente. Se demuestra que el tiempo de vida de la red mejora de forma significativa usando el criterio propuesto de eficiencia energética.

Ultra-wideband multistatic SAR for the detection and location of landmines

Techniques for improving the signal to clutter ratio of an. ultra-wideband SAR designed to detect small mine-like objects in the surface of the ground were investigated. In particular, images were collected using different bistatic antenna configurations in an attempt to decorrelate the clutter with respect to the targets. The images were converted to a reference depression angle, summed, and then converted to ground coordinates. The resulting target strengths were then compared with the amplitude distribution of the ground clutter to show the improvement obtained. While some improvement was demonstrated, this was for the relatively easy scenario of targets on the surface partially obscured by grass. Detection based on thresholding the raw RF signal (the bipolar response) rather than the envelope (baseband I-2 + Q(2)) was also considered to further enhance target-to-clutter ratios.

Temporal precision of interceptive action: differential effects of target size and speed

The duration of movements made to intercept moving targets decreases and movement speed increases when interception requires greater temporal precision. Changes in target size and target speed can have the same effect on required temporal precision, but the response to these changes differs: changes in target speed elicit larger changes in response speed. A possible explanation is that people attempt to strike the target in a central zone that does not vary much with variation in physical target size: the effective size of the target is relatively constant over changes in physical size. Three experiments are reported that test this idea. Participants performed two tasks: (1) strike a moving target with a bat moved perpendicular to the path of the target; (2) press on a force transducer when the target was in a location where it could be struck by the bat. Target speed was varied and target size held constant in experiment 1. Target speed and size were co-varied in experiment 2, keeping the required temporal precision constant. Target size was varied and target speed held constant in experiment 3 to give the same temporal precision as experiment 1. Duration of hitting movements decreased and maximum movement speed increased with increases in target speed and/or temporal precision requirements in all experiments. The effects were largest in experiment 1 and smallest in experiment 3. Analysis of a measure of effective target size (standard deviation of strike locations on the target) failed to support the hypothesis that performance differences could be explained in terms of effective size rather than actual physical size. In the pressing task, participants produced greater peak forces and shorter force pulses when the temporal precision required was greater, showing that the response to increasing temporal precision generalizes to different responses. It is concluded that target size and target speed have independent effects on performance.

A target-field method to design circular biplanar coils for asymmetric shim and gradient fields

The paper presents a method for designing circular, shielded biplanar coils that can generate any desired field. A particular feature of these coils is that the target field may be located asymmetrically within the coil. A transverse component of the magnetic field produced by the coil is made to match a prescribed target field over the surfaces of two concentric spheres (the diameter of spherical volume) that define the target field location. The paper shows winding patterns and fields for several gradient and shim coils. It examines the effect that the finite coil size has on the winding patterns, using a Fourier-transform calculation for comparison.

Overexpression of Leucyl Aminopeptidase in Plasmodium falciparum Parasites. Target for the antimalarial activity of bestatin

Malaria aminopeptidases are important in the generation and regulation of free amino acids that are used in protein anabolism and for maintaining osmotic stability within the infected erythrocyte. The intraerythrocytic development of malaria parasites is blocked when the activity of aminopeptidases is specifically inhibited by reagents such as bestatin. One of the major aminopeptidases of malaria parasites is a leucyl aminopeptidase of the M17 family. We reasoned that, when this enzyme was the target of bestatin inhibition, its overexpression in malaria cells would lead to a reduced sensitivity to the inhibitor. To address this supposition, transgenic Plasmodium falciparum parasites overexpressing the leucyl aminopeptidase were generated by transfection with a plasmid that housed the full-length gene. Transgenic parasites expressed a 65-kDa protein close to the predicted molecule size of 67.831 kDa for the introduced leucyl aminopeptidase, and immunofluorescence studies localized the protein to the cytosol, the location of the native enzyme. The product of the transgene was shown to be functionally active with cytosolic extracts of transgenic parasites exhibiting twice the leucyl aminopeptidase activity compared with wildtype parasites. In vitro inhibitor sensitivity assays demonstrated that the transgenic parasites were more resistant to bestatin (EC50 64 mu M) compared with the parent parasites (EC50 25 mu M). Overexpression of genes in malaria parasites would have general application in the identification and validation of targets for antimalarial drugs.

The global plant location decision

The global plant location decision is important since it involves the allocation of significant resources and may influence the long term competitiveness of firms. The decision is also complex, taking into account a wide range of factors. The decision should involve the consideration of both international business issues as well as manufacturing strategy. Firms may be seeking access to markets, to low cost labour, or new skills and competencies. In the past there has been some emphasis on firms offshoring production to lower cost regions. Case studies from the authors’ experience of advising clients in this decision show that for ‘luxury’ products, firms have chosen to invest further capacity in home country engineering and manufacturing to maintain quality and brand integrity, despite the fact that these locations are higher cost. On the other hand, for ‘standard’ products, firms have located additional capacity closer to target markets to access lower costs.

Identification Of Target Genes Using Gene Expression Profile Of Granulocytes From Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor κB (NF-κB), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets.

Stathmin 1, A Therapeutic Target In Esophageal Carcinoma?

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Deregulation Of Adipokines Related To Target Organ Damage On Resistant Hypertension.

Resistant hypertension (RHTN) includes patients with controlled blood pressure (BP) (CRHTN) and uncontrolled BP (UCRHTN). In fact, RHTN patients are more likely to have target organ damage (TOD), and resistin, leptin and adiponectin may affect BP control in these subjects. We assessed the relationship between adipokines levels and arterial stiffness, left ventricular hypertrophy (LVH) and microalbuminuria (MA). This cross-sectional study included CRHTN (n=51) and UCRHTN (n=38) patients for evaluating body mass index, ambulatory blood pressure monitoring, plasma adiponectin, leptin and resistin concentrations, pulse wave velocity (PWV), MA and echocardiography. Leptin and resistin levels were higher in UCRHTN, whereas adiponectin levels were lower in this same subgroup. Similarly, arterial stiffness, LVH and MA were higher in UCRHTN subgroup. Adiponectin levels negatively correlated with PWV (r=-0.42, P<0.01), and MA (r=-0.48, P<0.01) only in UCRHTN. Leptin was positively correlated with PWV (r=0.37, P=0.02) in UCRHTN subgroup, whereas resistin was not correlated with TOD in both subgroups. Adiponectin is associated with arterial stiffness and renal injury in UCRHTN patients, whereas leptin is associated with arterial stiffness in the same subgroup. Taken together, our results showed that those adipokines may contribute to vascular and renal damage in UCRHTN patients.

Evaluation Of The Location Of Capsules Swallowed With Food During The Pharyngeal Phase Triggering In Asymptomatic Adults.

To assess the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. The location of the bolus during the pharyngeal phase triggering provides information about the sensorimotor model of the beginning of deglutition onset. To evaluate the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. A videofluoroscopy swallowing study was carried out in 60 subjects (14 male and 46 female participants) aged between 27 and 55 years, who were evaluated with hard gelatin capsules #00 and #3 containing barium sulfate, swallowed with liquid food and pudding, in free volume. The first laryngeal elevation movement was the criterion to locate the pharyngeal phase triggering. Statistical analysis was based on the McNemar test. Capsule #3 presented higher percentage of location in the tongue dorsum compared to capsule #00, and capsule #00 presented higher percentage of location in the tongue base and vallecula compared to capsule #3. There was a difference between different capsules swallowed with liquid (p=0.016) and pudding (p=0.037). The capsule size influenced the location of the pharyngeal phase triggering. Smaller capsules started pharyngeal phase in the most anterior region (tongue dorsum) compared to larger capsules.

Preclinical Target Validation Using Patient-derived Cells.

The Structural Genomics Consortium (SGC) and its clinical, industry and disease-foundation partners are launching open-source preclinical translational medicine studies.

[comparative Study Between Fast And Slow Induction Of Propofol Given By Target-controlled Infusion: Expected Propofol Concentration At The Effect Site. Randomized Controlled Trial].

studies have shown that rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. the study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26min(-1)) with target concentration (Tc) at 2.0-μg.mL(-1) were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1μg.mL(-1), successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0μg.ml(-1)) at Es, and waited until loss of consciousness. in rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67±0.76 and 2.50±0.56μg.mL(-1), respectively, p=0.004). the predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site.

Androgen Therapy Reverses Injuries Caused By Ethanol Consumption In The Prostate: Testosterone As A Possible Target To Ethanol-related Disorders.

Chronic ethanol consumption leads to reproductive damages, since it can act directly in the tissues or indirectly, causing a hormonal imbalance. Prostate is a hormone-dependent gland and, consequently, susceptible to ethanol. The potential of testosterone therapy in the ethanol-related disorders was investigated in the prostate microenvironment. UChB rats aged 90 days were divided into 2 experimental groups (n=20): C: drinking water only and EtOH: drinking 10% (v/v) ethanol at >2 g/kg body weight/day+water. At 150 days old, 10 rats from each group received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks, constituting T and EtOH+T, while the remaining animals received corn oil as vehicle. Animals were euthanized at 180 days old, by decapitation. Blood was collected to obtain hormone concentrations and ventral prostate was dissected and processed for light microscope and molecular analyses. Ventral prostate weight, plasma testosterone and DHT and intraprostatic testosterone concentrations were increased after testosterone treatment. Plasma estradiol level was reduced in the EtOH+T. Inflammatory foci, metaplasia and epithelial atrophy were constantly found in the prostate of EtOH and were not observed after hormonal therapy. No differences were found in the expression of AR, ERβ and DACH-1. Additionally, testosterone treatment down-regulated ERα and increased the e-cadherin and α-actinin immunoreactivities. Testosterone was able to reverse damages caused by ethanol consumption in the prostate microenvironment and becomes a possible target to be investigated to ethanol-related disorders.