Local structure preserving sparse coding for infrared target recognition

PubMed Central

Han, Jing; Yue, Jiang; Zhang, Yi; Bai, Lianfa

2017-01-01

Sparse coding performs well in image classification. However, robust target recognition requires a lot of comprehensive template images and the sparse learning process is complex. We incorporate sparsity into a template matching concept to construct a local sparse structure matching (LSSM) model for general infrared target recognition. A local structure preserving sparse coding (LSPSc) formulation is proposed to simultaneously preserve the local sparse and structural information of objects. By adding a spatial local structure constraint into the classical sparse coding algorithm, LSPSc can improve the stability of sparse representation for targets and inhibit background interference in infrared images. Furthermore, a kernel LSPSc (K-LSPSc) formulation is proposed, which extends LSPSc to the kernel space to weaken the influence of the linear structure constraint in nonlinear natural data. Because of the anti-interference and fault-tolerant capabilities, both LSPSc- and K-LSPSc-based LSSM can implement target identification based on a simple template set, which just needs several images containing enough local sparse structures to learn a sufficient sparse structure dictionary of a target class. Specifically, this LSSM approach has stable performance in the target detection with scene, shape and occlusions variations. High performance is demonstrated on several datasets, indicating robust infrared target recognition in diverse environments and imaging conditions. PMID:28323824

Radiotherapy treatment planning: benefits of CT-MR image registration and fusion in tumor volume delineation.

PubMed

Djan, Igor; Petrović, Borislava; Erak, Marko; Nikolić, Ivan; Lucić, Silvija

2013-08-01

Development of imaging techniques, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), made great impact on radiotherapy treatment planning by improving the localization of target volumes. Improved localization allows better local control of tumor volumes, but also minimizes geographical misses. Mutual information is obtained by registration and fusion of images achieved manually or automatically. The aim of this study was to validate the CT-MRI image fusion method and compare delineation obtained by CT versus CT-MRI image fusion. The image fusion software (XIO CMS 4.50.0) was applied to delineate 16 patients. The patients were scanned on CT and MRI in the treatment position within an immobilization device before the initial treatment. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated on CT alone and on CT+MRI images consecutively and image fusion was obtained. Image fusion showed that CTV delineated on a CT image study set is mainly inadequate for treatment planning, in comparison with CTV delineated on CT-MRI fused image study set. Fusion of different modalities enables the most accurate target volume delineation. This study shows that registration and image fusion allows precise target localization in terms of GTV and CTV and local disease control.

Are national targets the right way to improve infection control practice?

PubMed

Millar, M

2009-12-01

The 'right way to improve infection control practice' should be cost-effective and lead to a fair distribution of infection control resources. Cost-effectiveness is a measure of aggregate 'good', and fairness emphasises similar treatment for individuals under similar circumstances. The UK national meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) target encourages National Health Service trusts to prioritise strategies aimed at MRSA BSI prevention. Under resource-limited conditions, the MRSA BSI target inevitably encourages deprioritisation of patients at risk of non-target healthcare-associated infection (HCAI), some of which are associated with an equal or larger burden of adverse outcome. Established healthcare improvement strategies, such as the Plan, Do, Study, Act (PDSA) cycle advocated by the Health Foundation, require the setting of aims (or targets). If we are to improve infection control practice then we need to decide on what to measure, how to measure it, and what the improvement (target) should be. In selecting targets for infection prevention, account should be taken of the contribution of HCAI to adverse health outcomes overall. Human risk compensation behaviour and microbial adaptation may both counteract the overall benefit of infection targets isolated from overall outcomes. Risk taking is part of a healthy healthcare system. We must be careful not to isolate HCAI outcomes from overall outcomes or to isolate 'risk takers' from 'risk controllers'. We must try to limit the scope for human risk compensation and we must watch out for microbial adaptation. Targets should be set locally, taking account of fairness and cost-effectiveness. Locally relevant information is key; positive incentives work best.

Scan statistics with local vote for target detection in distributed system

NASA Astrophysics Data System (ADS)

Luo, Junhai; Wu, Qi

2017-12-01

Target detection has occupied a pivotal position in distributed system. Scan statistics, as one of the most efficient detection methods, has been applied to a variety of anomaly detection problems and significantly improves the probability of detection. However, scan statistics cannot achieve the expected performance when the noise intensity is strong, or the signal emitted by the target is weak. The local vote algorithm can also achieve higher target detection rate. After the local vote, the counting rule is always adopted for decision fusion. The counting rule does not use the information about the contiguity of sensors but takes all sensors' data into consideration, which makes the result undesirable. In this paper, we propose a scan statistics with local vote (SSLV) method. This method combines scan statistics with local vote decision. Before scan statistics, each sensor executes local vote decision according to the data of its neighbors and its own. By combining the advantages of both, our method can obtain higher detection rate in low signal-to-noise ratio environment than the scan statistics. After the local vote decision, the distribution of sensors which have detected the target becomes more intensive. To make full use of local vote decision, we introduce a variable-step-parameter for the SSLV. It significantly shortens the scan period especially when the target is absent. Analysis and simulations are presented to demonstrate the performance of our method.

Anchor-Free Localization Method for Mobile Targets in Coal Mine Wireless Sensor Networks

PubMed Central

Pei, Zhongmin; Deng, Zhidong; Xu, Shuo; Xu, Xiao

2009-01-01

Severe natural conditions and complex terrain make it difficult to apply precise localization in underground mines. In this paper, an anchor-free localization method for mobile targets is proposed based on non-metric multi-dimensional scaling (Multi-dimensional Scaling: MDS) and rank sequence. Firstly, a coal mine wireless sensor network is constructed in underground mines based on the ZigBee technology. Then a non-metric MDS algorithm is imported to estimate the reference nodes’ location. Finally, an improved sequence-based localization algorithm is presented to complete precise localization for mobile targets. The proposed method is tested through simulations with 100 nodes, outdoor experiments with 15 ZigBee physical nodes, and the experiments in the mine gas explosion laboratory with 12 ZigBee nodes. Experimental results show that our method has better localization accuracy and is more robust in underground mines. PMID:22574048

Anchor-free localization method for mobile targets in coal mine wireless sensor networks.

PubMed

Pei, Zhongmin; Deng, Zhidong; Xu, Shuo; Xu, Xiao

2009-01-01

Severe natural conditions and complex terrain make it difficult to apply precise localization in underground mines. In this paper, an anchor-free localization method for mobile targets is proposed based on non-metric multi-dimensional scaling (Multi-dimensional Scaling: MDS) and rank sequence. Firstly, a coal mine wireless sensor network is constructed in underground mines based on the ZigBee technology. Then a non-metric MDS algorithm is imported to estimate the reference nodes' location. Finally, an improved sequence-based localization algorithm is presented to complete precise localization for mobile targets. The proposed method is tested through simulations with 100 nodes, outdoor experiments with 15 ZigBee physical nodes, and the experiments in the mine gas explosion laboratory with 12 ZigBee nodes. Experimental results show that our method has better localization accuracy and is more robust in underground mines.

Observer efficiency in free-localization tasks with correlated noise.

PubMed

Abbey, Craig K; Eckstein, Miguel P

2014-01-01

The efficiency of visual tasks involving localization has traditionally been evaluated using forced choice experiments that capitalize on independence across locations to simplify the performance of the ideal observer. However, developments in ideal observer analysis have shown how an ideal observer can be defined for free-localization tasks, where a target can appear anywhere in a defined search region and subjects respond by localizing the target. Since these tasks are representative of many real-world search tasks, it is of interest to evaluate the efficiency of observer performance in them. The central question of this work is whether humans are able to effectively use the information in a free-localization task relative to a similar task where target location is fixed. We use a yes-no detection task at a cued location as the reference for this comparison. Each of the tasks is evaluated using a Gaussian target profile embedded in four different Gaussian noise backgrounds having power-law noise power spectra with exponents ranging from 0 to 3. The free localization task had a square 6.7° search region. We report on two follow-up studies investigating efficiency in a detect-and-localize task, and the effect of processing the white-noise backgrounds. In the fixed-location detection task, we find average observer efficiency ranges from 35 to 59% for the different noise backgrounds. Observer efficiency improves dramatically in the tasks involving localization, ranging from 63 to 82% in the forced localization tasks and from 78 to 92% in the detect-and- localize tasks. Performance in white noise, the lowest efficiency condition, was improved by filtering to give them a power-law exponent of 2. Classification images, used to examine spatial frequency weights for the tasks, show better tuning to ideal weights in the free-localization tasks. The high absolute levels of efficiency suggest that observers are well-adapted to free-localization tasks.

Observer efficiency in free-localization tasks with correlated noise

PubMed Central

Abbey, Craig K.; Eckstein, Miguel P.

2014-01-01

The efficiency of visual tasks involving localization has traditionally been evaluated using forced choice experiments that capitalize on independence across locations to simplify the performance of the ideal observer. However, developments in ideal observer analysis have shown how an ideal observer can be defined for free-localization tasks, where a target can appear anywhere in a defined search region and subjects respond by localizing the target. Since these tasks are representative of many real-world search tasks, it is of interest to evaluate the efficiency of observer performance in them. The central question of this work is whether humans are able to effectively use the information in a free-localization task relative to a similar task where target location is fixed. We use a yes-no detection task at a cued location as the reference for this comparison. Each of the tasks is evaluated using a Gaussian target profile embedded in four different Gaussian noise backgrounds having power-law noise power spectra with exponents ranging from 0 to 3. The free localization task had a square 6.7° search region. We report on two follow-up studies investigating efficiency in a detect-and-localize task, and the effect of processing the white-noise backgrounds. In the fixed-location detection task, we find average observer efficiency ranges from 35 to 59% for the different noise backgrounds. Observer efficiency improves dramatically in the tasks involving localization, ranging from 63 to 82% in the forced localization tasks and from 78 to 92% in the detect-and- localize tasks. Performance in white noise, the lowest efficiency condition, was improved by filtering to give them a power-law exponent of 2. Classification images, used to examine spatial frequency weights for the tasks, show better tuning to ideal weights in the free-localization tasks. The high absolute levels of efficiency suggest that observers are well-adapted to free-localization tasks. PMID:24817854

Focusing, Sustaining, and Switching Attention

DTIC Science & Technology

2013-09-12

selective attention . Aim 2. Effects on non-spatial features. We measured whether selective attention to an ongoing target improves with time when...talk]. Shinn-Cunningham BG (2013). "Spatial hearing in rooms: Effects on selective auditory attention and sound localization," Neuroscience for...hypothesis that room reverberation interferes with selective attention , 2) whether selective attention to an ongoing target improves with time when

Location detection and tracking of moving targets by a 2D IR-UWB radar system.

PubMed

Nguyen, Van-Han; Pyun, Jae-Young

2015-03-19

In indoor environments, the Global Positioning System (GPS) and long-range tracking radar systems are not optimal, because of signal propagation limitations in the indoor environment. In recent years, the use of ultra-wide band (UWB) technology has become a possible solution for object detection, localization and tracking in indoor environments, because of its high range resolution, compact size and low cost. This paper presents improved target detection and tracking techniques for moving objects with impulse-radio UWB (IR-UWB) radar in a short-range indoor area. This is achieved through signal-processing steps, such as clutter reduction, target detection, target localization and tracking. In this paper, we introduce a new combination consisting of our proposed signal-processing procedures. In the clutter-reduction step, a filtering method that uses a Kalman filter (KF) is proposed. Then, in the target detection step, a modification of the conventional CLEAN algorithm which is used to estimate the impulse response from observation region is applied for the advanced elimination of false alarms. Then, the output is fed into the target localization and tracking step, in which the target location and trajectory are determined and tracked by using unscented KF in two-dimensional coordinates. In each step, the proposed methods are compared to conventional methods to demonstrate the differences in performance. The experiments are carried out using actual IR-UWB radar under different scenarios. The results verify that the proposed methods can improve the probability and efficiency of target detection and tracking.

Networking grassroots efforts to improve safety and health in informal economy workplaces in Asia.

PubMed

Kawakami, Tsuyoshi

2006-01-01

Many workers in Asia are in the informal economy. They often work in substandard conditions, exposed to hazards in the workplace. Learning from the recent successes of participatory training programmes to improve safety and health in Asia, the ILO has strengthened its partnership efforts with local people to improve safety and health of informal economy workplaces. The target groups were: (1) home workplaces in Cambodia and Thailand, (2) salt fields and fishing villages in Cambodia where many young workers are working, and (3) small construction sites in Cambodia, Laos, Mongolia, Thailand and Vietnam. The walk-through survey results showed that the workers and owners in the target informal economy workplaces had the strong will to improve safety and health at their own initiatives and needed practical support. In the participatory, action-oriented training workshops carried out, the participated workers and owners were able to identify their priority safety and health actions. Commonly identified were clear and safe transport ways, safer handling of hazardous substances, basic welfare needs such as drinking water and sanitary toilets, and work posture. The follow-up visits confirmed that many of the proposed actions were actually taken by using low-cost available materials. These positive changes were possible by applying the participatory training tools such as illustrated checklists and extensive use of photographs showing local good examples and placing emphasis on facilitator roles of trainers. In conclusion, the target informal economy workplaces in Asia made positive changes in safety and health through the participatory, action-oriented training focusing on local initiative and low-cost improvement measures. Local network support mechanisms to share lessons from good practices played essential roles in encouraging the voluntary implementation of practical improvement actions. It is important to increase our joint efforts to reach more informal economy workplaces in industrially developing countries and provide practical support measures focusing on local self-help initiatives.

Reducing inequalities in access to health care: developing a toolkit through action research.

PubMed

Goyder, E C; Blank, L; Ellis, E; Furber, A; Peters, J; Sartain, K; Massey, C

2005-10-01

Healthcare organisations are expected both to monitor inequalities in access to health services and also to act to improve access and increase equity in service provision. Locally developed action research projects with an explicit objective of reducing inequalities in access. Eight different health care services in the Yorkshire and Humber region, including community based palliative care, general practice asthma care, hospital based cardiology clinics, and termination of pregnancy services. Changes in service provision, increasing attendance rates in targeted groups. Local teams identified the population concerned and appropriate interventions using both published and grey literature. Where change to service provision was achieved, local data were collected to monitor the impact of service change. A number of evidence based changes to service provision were proposed and implemented with variable success. Service uptake increased in some of the targeted populations. Interventions to improve access must be sensitive to local settings and need both practical and managerial support to succeed. It is particularly difficult to improve access effectively if services are already struggling to meet current demand. Key elements for successful interventions included effective local leadership, identification of an intervention which is both evidence based and locally practicable, and identification of additional resources to support increased activity. A "toolkit" has been developed to support the identification and implementation of appropriate changes.

Adjuvant Vascular Endothelial Growth Factor-targeted Therapy in Renal Cell Carcinoma: A Systematic Review and Pooled Analysis.

PubMed

Sun, Maxine; Marconi, Lorenzo; Eisen, Tim; Escudier, Bernard; Giles, Rachel H; Haas, Naomi B; Harshman, Lauren C; Quinn, David I; Larkin, James; Pal, Sumanta K; Powles, Thomas; Ryan, Christopher W; Sternberg, Cora N; Uzzo, Robert; Choueiri, Toni K; Bex, Axel

2018-05-18

Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal cell carcinoma (RCC). To systematically evaluate the current evidence regarding the therapeutic benefit (disease-free survival [DFS] and overall survival [OS]) and grade 3-4 adverse events (AEs) for adjuvant VEGFR-targeted therapy for resected localized RCC. A critical review of PubMed/Medline, Embase, and the Cochrane Library in January 2018 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was performed. We identified reports and reviewed them according to the Consolidated Standards of Reporting Trials and Standards for the Reporting of Diagnostic Accuracy Studies criteria. Of eight full-text articles that were eligible for inclusion, five studies (two of five were updated analyses) were retained in the final synthesis. Study characteristics were abstracted and the number needed to treat (NNT) per trial was estimated. The three randomized controlled phase III trials included the following comparisons: sunitinib versus placebo or sorafenib versus placebo (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma [ASSURE] study, n=1943), sunitinib versus placebo (S-TRAC, n=615), and pazopanib versus placebo (Pazopanib As Adjuvant Therapy in Localized/Locally Advanced RCC After Nephrectomy study, n=1135). The NNT ranged from 10 (S-TRAC) to 137 (ASSURE study). The pooled analysis showed that VEGFR-targeted therapy was not statistically significantly associated with improved DFS (hazard ratio [HR random ]: 0.92, 95% confidence interval [CI]: 0.82-1.03, p=0.16) or OS (HR random : 0.98, 95% CI: 0.84-1.15, p=0.84) compared with the control group. The adjuvant therapy group experienced significantly higher odds of grade 3-4 AEs (OR random : 5.89, 95% CI: 4.85-7.15, p<0.001). In exploratory analyses focusing on patients who started on the full-dose regimen, DFS was improved in patients who received adjuvant therapy (HR random : 0.83, 95% CI: 0.73-0.95, p=0.005). This pooled analysis of reported randomized trials did not reveal a statistically significant effect between adjuvant VEGFR-targeted therapy and improved DFS or OS in patients with intermediate/high-risk local or regional fully resected RCC. Improvement in DFS may be more likely with the use of full-dose regimens, pending further results. However, adjuvant treatment was associated with high-grade AEs. Vascular endothelial growth factor receptor-targeted therapy after nephrectomy for localized kidney cancer is not associated with consistent improvements in delaying cancer recurrence or prolonging life and comes at the expense of potentially significant side effects. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Improving nanoparticle diffusion through tumor collagen matrix by photo-thermal gold nanorods

NASA Astrophysics Data System (ADS)

Raeesi, Vahid; Chan, Warren C. W.

2016-06-01

Collagen (I) impairs the targeting of nanoparticles to tumor cells by obstructing their diffusion inside dense tumor interstitial matrix. This potentially makes large nanoparticles (>50 nm) reside near the tumor vessels and thereby compromises their functionality. Here we propose a strategy to locally improve nanoparticle transport inside collagen (I) component of the tumor tissue. We first used heat generating gold nanorods to alter collagen (I) matrix by local temperature elevation. We then explored this impact on the transport of 50 nm and 120 nm inorganic nanoparticles inside collagen (I). We demonstrated an increase in average diffusivity of 50 nm and 120 nm in the denatured collagen (I) by ~14 and ~21 fold, respectively, compared to intact untreated collagen (I) matrix. This study shows how nanoparticle-mediated hyperthermia inside tumor tissue can improve the transport of large nanoparticles through collagen (I) matrix. The ability to increase nanoparticles diffusion inside tumor stroma allows their targeting or other functionalities to take effect, thereby significantly improving cancer therapeutic or diagnostic outcome.Collagen (I) impairs the targeting of nanoparticles to tumor cells by obstructing their diffusion inside dense tumor interstitial matrix. This potentially makes large nanoparticles (>50 nm) reside near the tumor vessels and thereby compromises their functionality. Here we propose a strategy to locally improve nanoparticle transport inside collagen (I) component of the tumor tissue. We first used heat generating gold nanorods to alter collagen (I) matrix by local temperature elevation. We then explored this impact on the transport of 50 nm and 120 nm inorganic nanoparticles inside collagen (I). We demonstrated an increase in average diffusivity of 50 nm and 120 nm in the denatured collagen (I) by ~14 and ~21 fold, respectively, compared to intact untreated collagen (I) matrix. This study shows how nanoparticle-mediated hyperthermia inside tumor tissue can improve the transport of large nanoparticles through collagen (I) matrix. The ability to increase nanoparticles diffusion inside tumor stroma allows their targeting or other functionalities to take effect, thereby significantly improving cancer therapeutic or diagnostic outcome. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08463f

Local ensemble transform Kalman filter for ionospheric data assimilation: Observation influence analysis during a geomagnetic storm event

NASA Astrophysics Data System (ADS)

Durazo, Juan A.; Kostelich, Eric J.; Mahalov, Alex

2017-09-01

We propose a targeted observation strategy, based on the influence matrix diagnostic, that optimally selects where additional observations may be placed to improve ionospheric forecasts. This strategy is applied in data assimilation observing system experiments, where synthetic electron density vertical profiles, which represent those of Constellation Observing System for Meteorology, Ionosphere, and Climate/Formosa satellite 3, are assimilated into the Thermosphere-Ionosphere-Electrodynamics General Circulation Model using the local ensemble transform Kalman filter during the 26 September 2011 geomagnetic storm. During each analysis step, the observation vector is augmented with five synthetic vertical profiles optimally placed to target electron density errors, using our targeted observation strategy. Forecast improvement due to assimilation of augmented vertical profiles is measured with the root-mean-square error (RMSE) of analyzed electron density, averaged over 600 km regions centered around the augmented vertical profile locations. Assimilating vertical profiles with targeted locations yields about 60%-80% reduction in electron density RMSE, compared to a 15% average reduction when assimilating randomly placed vertical profiles. Assimilating vertical profiles whose locations target the zonal component of neutral winds (Un) yields on average a 25% RMSE reduction in Un estimates, compared to a 2% average improvement obtained with randomly placed vertical profiles. These results demonstrate that our targeted strategy can improve data assimilation efforts during extreme events by detecting regions where additional observations would provide the largest benefit to the forecast.

U.S. Assistance to Yemen: Actions Needed to Improve Oversight of Emergency Food Aid and Assess Security Assistance

DTIC Science & Technology

2013-03-01

annual targets between fiscal years 2008 and 2011 for the number of individuals in Yemen benefiting from food donations. However, reports to Congress...annual performance targets three times for the number of individuals in Yemen benefiting from food donations, reports to Congress about the program...security to several hundred locally employed staff. However, the embassy has deemed other steps proposed by locally employed staff, including telework and

Electromagnetic redesign of the HYPERcollar applicator: toward improved deep local head-and-neck hyperthermia.

PubMed

Togni, P; Rijnen, Z; Numan, W C M; Verhaart, R F; Bakker, J F; van Rhoon, G C; Paulides, M M

2013-09-07

Accumulating evidence shows that hyperthermia improves head-and-neck cancer treatment. Over the last decade, we introduced a radiofrequency applicator, named HYPERcollar, which enables local heating also of deep locations in this region. Based on clinical experience, we redesigned the HYPERcollar for improved comfort, reproducibility and operator handling. In the current study, we analyze the redesign from an electromagnetic point of view. We show that a higher number of antennas and their repositioning allow for a substantially improved treatment quality. Combined with the much better reproducibility of the water bolus, this will substantially minimize the risk of underexposure. All improvements combined enable a reduction of hot-spot prominence (hot-spot to target SAR quotient) by 32% at an average of 981 W, which drastically reduces the probability for system power to become a treatment limiting source. Moreover, the power deposited in the target selectively can be increased by more than twofold. Hence, we expect that the HYPERcollar redesign currently under construction allows us to double the clinically applied power to the target while reducing the hot-spots, resulting in higher temperatures and, consequently, better clinical outcome.

Single photon emission computed tomographic studies (SPECT) of hepatic arterial perfusion scintigraphy (HAPS) in patients with colorectal liver metastases: improved tumour targetting by microspheres with angiotensin II.

PubMed

Goldberg, J A; Bradnam, M S; Kerr, D J; McKillop, J H; Bessent, R G; McArdle, C S; Willmott, N; George, W D

1987-12-01

As intra-arterial chemotherapy for liver metastases of colorectal origin becomes accepted, methods of further improving drug delivery to the tumour have been devised. Degradable microspheres have been shown to reduce regional blood flow by transient arteriolar capillary block, thereby improving uptake of a co-administered drug, when injected into the hepatic artery. In our study of five patients, we combined hepatic arterial perfusion scintigraphy (HAPS) and SPECT to assess the localization of approximately 1 X 10(5) labelled microspheres of human serum albumin (99Tcm MSA) in tumour. In addition, in three patients, we assessed the effect of an intra-arterial infusion of the vasoactive agent angiotension II during HAPS. Results were interpreted by comparing transaxial slices with corresponding slices of a tin colloid liver-spleen scan. Two of five patients showed good localization of 99Tcm MSA in tumour without an angiotensin II infusion. Of the three patients receiving angiotensin II, all showed good tumour targetting with the vasoconstrictor compared with only one of these three before its use. Thus, hepatic arterial infusion of angiotensin II greatly improves microsphere localization in tumour in some patients with colorectal liver metastases. This technique may be useful in the assessment of tumour targetting before and during locoregional therapy.

Infrared Ship Target Segmentation Based on Spatial Information Improved FCM.

PubMed

Bai, Xiangzhi; Chen, Zhiguo; Zhang, Yu; Liu, Zhaoying; Lu, Yi

2016-12-01

Segmentation of infrared (IR) ship images is always a challenging task, because of the intensity inhomogeneity and noise. The fuzzy C-means (FCM) clustering is a classical method widely used in image segmentation. However, it has some shortcomings, like not considering the spatial information or being sensitive to noise. In this paper, an improved FCM method based on the spatial information is proposed for IR ship target segmentation. The improvements include two parts: 1) adding the nonlocal spatial information based on the ship target and 2) using the spatial shape information of the contour of the ship target to refine the local spatial constraint by Markov random field. In addition, the results of K -means are used to initialize the improved FCM method. Experimental results show that the improved method is effective and performs better than the existing methods, including the existing FCM methods, for segmentation of the IR ship images.

Ocean Ambient Noise Studies for Improved Sonar Processing

DTIC Science & Technology

2012-09-30

this shortfall, the conceptual basis of using multipath arrivals to enhance target localization still holds promise. In this project, the emphasis...and K. Folkert, “Three- dimensional localization of sperm whales using a single hydrophone”, J. Acous. Soc. Am. 120, 2355-2365 (2006). [Holmes

A Modified Magnetic Gradient Contraction Based Method for Ferromagnetic Target Localization

PubMed Central

Wang, Chen; Zhang, Xiaojuan; Qu, Xiaodong; Pan, Xiao; Fang, Guangyou; Chen, Luzhao

2016-01-01

The Scalar Triangulation and Ranging (STAR) method, which is based upon the unique properties of magnetic gradient contraction, is a high real-time ferromagnetic target localization method. Only one measurement point is required in the STAR method and it is not sensitive to changes in sensing platform orientation. However, the localization accuracy of the method is limited by the asphericity errors and the inaccurate value of position leads to larger errors in the estimation of magnetic moment. To improve the localization accuracy, a modified STAR method is proposed. In the proposed method, the asphericity errors of the traditional STAR method are compensated with an iterative algorithm. The proposed method has a fast convergence rate which meets the requirement of high real-time localization. Simulations and field experiments have been done to evaluate the performance of the proposed method. The results indicate that target parameters estimated by the modified STAR method are more accurate than the traditional STAR method. PMID:27999322

Device-Free Localization via an Extreme Learning Machine with Parameterized Geometrical Feature Extraction.

PubMed

Zhang, Jie; Xiao, Wendong; Zhang, Sen; Huang, Shoudong

2017-04-17

Device-free localization (DFL) is becoming one of the new technologies in wireless localization field, due to its advantage that the target to be localized does not need to be attached to any electronic device. In the radio-frequency (RF) DFL system, radio transmitters (RTs) and radio receivers (RXs) are used to sense the target collaboratively, and the location of the target can be estimated by fusing the changes of the received signal strength (RSS) measurements associated with the wireless links. In this paper, we will propose an extreme learning machine (ELM) approach for DFL, to improve the efficiency and the accuracy of the localization algorithm. Different from the conventional machine learning approaches for wireless localization, in which the above differential RSS measurements are trivially used as the only input features, we introduce the parameterized geometrical representation for an affected link, which consists of its geometrical intercepts and differential RSS measurement. Parameterized geometrical feature extraction (PGFE) is performed for the affected links and the features are used as the inputs of ELM. The proposed PGFE-ELM for DFL is trained in the offline phase and performed for real-time localization in the online phase, where the estimated location of the target is obtained through the created ELM. PGFE-ELM has the advantages that the affected links used by ELM in the online phase can be different from those used for training in the offline phase, and can be more robust to deal with the uncertain combination of the detectable wireless links. Experimental results show that the proposed PGFE-ELM can improve the localization accuracy and learning speed significantly compared with a number of the existing machine learning and DFL approaches, including the weighted K-nearest neighbor (WKNN), support vector machine (SVM), back propagation neural network (BPNN), as well as the well-known radio tomographic imaging (RTI) DFL approach.

Device-Free Localization via an Extreme Learning Machine with Parameterized Geometrical Feature Extraction

PubMed Central

Zhang, Jie; Xiao, Wendong; Zhang, Sen; Huang, Shoudong

2017-01-01

Device-free localization (DFL) is becoming one of the new technologies in wireless localization field, due to its advantage that the target to be localized does not need to be attached to any electronic device. In the radio-frequency (RF) DFL system, radio transmitters (RTs) and radio receivers (RXs) are used to sense the target collaboratively, and the location of the target can be estimated by fusing the changes of the received signal strength (RSS) measurements associated with the wireless links. In this paper, we will propose an extreme learning machine (ELM) approach for DFL, to improve the efficiency and the accuracy of the localization algorithm. Different from the conventional machine learning approaches for wireless localization, in which the above differential RSS measurements are trivially used as the only input features, we introduce the parameterized geometrical representation for an affected link, which consists of its geometrical intercepts and differential RSS measurement. Parameterized geometrical feature extraction (PGFE) is performed for the affected links and the features are used as the inputs of ELM. The proposed PGFE-ELM for DFL is trained in the offline phase and performed for real-time localization in the online phase, where the estimated location of the target is obtained through the created ELM. PGFE-ELM has the advantages that the affected links used by ELM in the online phase can be different from those used for training in the offline phase, and can be more robust to deal with the uncertain combination of the detectable wireless links. Experimental results show that the proposed PGFE-ELM can improve the localization accuracy and learning speed significantly compared with a number of the existing machine learning and DFL approaches, including the weighted K-nearest neighbor (WKNN), support vector machine (SVM), back propagation neural network (BPNN), as well as the well-known radio tomographic imaging (RTI) DFL approach. PMID:28420187

Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landrace and cultivars

USDA-ARS?s Scientific Manuscript database

Domesticated crops have experienced strong human-driven selection aimed at the development of improved varieties adapted to local conditions. To detect regions of the wheat genome subject to selection during improvement, we developed a high-throughput array to interrogate 9,000 gene-associated DNA m...

Audio-visual speech intelligibility benefits with bilateral cochlear implants when talker location varies.

PubMed

van Hoesel, Richard J M

2015-04-01

One of the key benefits of using cochlear implants (CIs) in both ears rather than just one is improved localization. It is likely that in complex listening scenes, improved localization allows bilateral CI users to orient toward talkers to improve signal-to-noise ratios and gain access to visual cues, but to date, that conjecture has not been tested. To obtain an objective measure of that benefit, seven bilateral CI users were assessed for both auditory-only and audio-visual speech intelligibility in noise using a novel dynamic spatial audio-visual test paradigm. For each trial conducted in spatially distributed noise, first, an auditory-only cueing phrase that was spoken by one of four talkers was selected and presented from one of four locations. Shortly afterward, a target sentence was presented that was either audio-visual or, in another test configuration, audio-only and was spoken by the same talker and from the same location as the cueing phrase. During the target presentation, visual distractors were added at other spatial locations. Results showed that in terms of speech reception thresholds (SRTs), the average improvement for bilateral listening over the better performing ear alone was 9 dB for the audio-visual mode, and 3 dB for audition-alone. Comparison of bilateral performance for audio-visual and audition-alone showed that inclusion of visual cues led to an average SRT improvement of 5 dB. For unilateral device use, no such benefit arose, presumably due to the greatly reduced ability to localize the target talker to acquire visual information. The bilateral CI speech intelligibility advantage over the better ear in the present study is much larger than that previously reported for static talker locations and indicates greater everyday speech benefits and improved cost-benefit than estimated to date.

Utilization of targeted near-infrared molecular imaging to improve pulmonary metastasectomy of osteosarcomas

NASA Astrophysics Data System (ADS)

Predina, Jarrod D.; Newton, Andrew; Deshpande, Charuhas; Low, Philip; Singhal, Sunil

2018-01-01

Pulmonary metastasectomy for osteosarcoma provides a select group of patients an opportunity for long-term survival and possible cure. Unfortunately, a complete metastasectomy is challenging due an inability to accurately identify lesions that lay below the threshold of preoperative imaging or intraoperative visual and tactile inspection. Growing evidence suggests that osteosarcomas express a number of unique molecular markers, including the folate receptor alpha. In this case report, we describe the application of a folate receptor-targeted, near-infrared optical contrast agent (OTL38) to improve osteosarcoma localization during minimally invasive pulmonary resection. In addition to localizing preoperatively identified lesions, this technology helped identify additional disease that was undetected on preoperative imaging or with traditional intraoperative techniques. This report marks the first successful utilization of a molecular imaging probe useful for osteosarcomas. This technology may provide a unique approach to improve pulmonary metastasectomy of osteosarcomas.

Development In Drug Targeting And Delivery In Cervical Cancer.

PubMed

Aggarwal, Urvashi; Goyal, Amit Kumar; Rath, Goutam

2017-10-09

Cervical cancer is the second most common cancer in women. Standard treatment options available for cervical cancer including chemotherapy, surgery and radiation therapy associated with their own side effects and toxicities. Tumor-targeted delivery of anticancer drugs is perhaps one of the most appropriate strategies to achieve optimal outcomes from treatment and improve quality of life. Recently nanocarriers based drug delivery systems owing to their unique properties have been extensively investigated for anticancer drug delivery. In addition to that addressing the anatomical significance of cervical cancer, various local drug delivery strategies for the cancer treatment are introduced like: gels, nanoparticles, polymeric films, rods and wafers, lipid based nanocarrier. Localized drug delivery systems allows passive drug targeting results in high drug concentration at the target site. Further they can be tailor made to achieve both sustained and controlled release behavior, substantially improving therapeutic outcomes and minimizing side effects. This review summarizes the meaningful advances in drug delivery strategies to treat cervical cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multiple targets detection method in detection of UWB through-wall radar

NASA Astrophysics Data System (ADS)

Yang, Xiuwei; Yang, Chuanfa; Zhao, Xingwen; Tian, Xianzhong

2017-11-01

In this paper, the problems and difficulties encountered in the detection of multiple moving targets by UWB radar are analyzed. The experimental environment and the penetrating radar system are established. An adaptive threshold method based on local area is proposed to effectively filter out clutter interference The objective of the moving target is analyzed, and the false target is further filtered out by extracting the target feature. Based on the correlation between the targets, the target matching algorithm is proposed to improve the detection accuracy. Finally, the effectiveness of the above method is verified by practical experiment.

Increasing breastfeeding and reducing smoking in pregnancy: a social marketing success improving life chances for children.

PubMed

Lowry, R J; Billett, A; Buchanan, C; Whiston, Sandra

2009-11-01

The aim of this study is to evaluate an intervention using social marketing principles to increase breastfeeding and reduce smoking during pregnancy in a population to improve life chances for children born in a town in north east England. Breastfeeding and smoking cessation attendance rates were measured against targets set in a government-local health authority agreement. Targets were bettered in both breastfeeding and smoking cessation. This social marketing-based approach is successful.

A Novel System for Correction of Relative Angular Displacement between Airborne Platform and UAV in Target Localization

PubMed Central

Liu, Chenglong; Liu, Jinghong; Song, Yueming; Liang, Huaidan

2017-01-01

This paper provides a system and method for correction of relative angular displacements between an Unmanned Aerial Vehicle (UAV) and its onboard strap-down photoelectric platform to improve localization accuracy. Because the angular displacements have an influence on the final accuracy, by attaching a measuring system to the platform, the texture image of platform base bulkhead can be collected in a real-time manner. Through the image registration, the displacement vector of the platform relative to its bulkhead can be calculated to further determine angular displacements. After being decomposed and superposed on the three attitude angles of the UAV, the angular displacements can reduce the coordinate transformation errors and thus improve the localization accuracy. Even a simple kind of method can improve the localization accuracy by 14.3%. PMID:28273845

A Novel System for Correction of Relative Angular Displacement between Airborne Platform and UAV in Target Localization.

PubMed

Liu, Chenglong; Liu, Jinghong; Song, Yueming; Liang, Huaidan

2017-03-04

This paper provides a system and method for correction of relative angular displacements between an Unmanned Aerial Vehicle (UAV) and its onboard strap-down photoelectric platform to improve localization accuracy. Because the angular displacements have an influence on the final accuracy, by attaching a measuring system to the platform, the texture image of platform base bulkhead can be collected in a real-time manner. Through the image registration, the displacement vector of the platform relative to its bulkhead can be calculated to further determine angular displacements. After being decomposed and superposed on the three attitude angles of the UAV, the angular displacements can reduce the coordinate transformation errors and thus improve the localization accuracy. Even a simple kind of method can improve the localization accuracy by 14.3%.

Combining Targeted Agents With Modern Radiotherapy in Soft Tissue Sarcomas

PubMed Central

Wong, Philip; Houghton, Peter; Kirsch, David G.; Finkelstein, Steven E.; Monjazeb, Arta M.; Xu-Welliver, Meng; Dicker, Adam P.; Ahmed, Mansoor; Vikram, Bhadrasain; Teicher, Beverly A.; Coleman, C. Norman; Machtay, Mitchell; Curran, Walter J.

2014-01-01

Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes. PMID:25326640

Time-Resolved Intrafraction Target Translations and Rotations During Stereotactic Liver Radiation Therapy: Implications for Marker-based Localization Accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertholet, Jenny, E-mail: jennbe@rm.dk; Worm, Esben S.; Fledelius, Walther

Purpose: Image guided liver stereotactic body radiation therapy (SBRT) often relies on implanted fiducial markers. The target localization accuracy decreases with increased marker-target distance. This may occur partly because of liver rotations. The aim of this study was to examine time-resolved translations and rotations of liver marker constellations and investigate if time-resolved intrafraction rotational corrections can improve localization accuracy in liver SBRT. Methods and Materials: Twenty-nine patients with 3 implanted markers received SBRT in 3 to 6 fractions. The time-resolved trajectory of each marker was estimated from the projections of 1 to 3 daily cone beam computed tomography scans andmore » used to calculate the translation and rotation of the marker constellation. In all cone beam computed tomography projections, the time-resolved position of each marker was predicted from the position of another surrogate marker by assuming that the marker underwent either (1) the same translation as the surrogate marker; or (2) the same translation as the surrogate marker corrected by the rotation of the marker constellation. The localization accuracy was quantified as the root-mean-square error (RMSE) between the estimated and the actual marker position. For comparison, the RMSE was also calculated when the marker's position was estimated as its mean position for all the projections. Results: The mean translational and rotational range (2nd-98th percentile) was 2.0 mm/3.9° (right-left), 9.2 mm/2.9° (superior-inferior), 4.0 mm/4.0° (anterior-posterior), and 10.5 mm (3-dimensional). Rotational corrections decreased the mean 3-dimensional RMSE from 0.86 mm to 0.54 mm (P<.001) and halved the RMSE increase per millimeter increase in marker distance. Conclusions: Intrafraction rotations during liver SBRT reduce the accuracy of marker-guided target localization. Rotational correction can improve the localization accuracy with a factor of approximately 2 for large marker-target distances.« less

Does Information Improve the Health Behavior of Adults Targeted by a Conditional Transfer Program?

ERIC Educational Resources Information Center

Avitabile, Ciro

2012-01-01

We use data from the evaluation sample of Mexico's Food Assistance Program (PAL) to study whether including the attendance at health and nutrition classes among the requirements for receiving a transfer affects the health behavior of adults living in localities targeted by the program. The experimental trial has four different treatment types,…

Managing Systemic Curriculum Change: A Critical Analysis of Hong Kong's Target-Oriented Curriculum Initiative.

ERIC Educational Resources Information Center

Carless, David

1997-01-01

Describes Hong Kong's Target-Oriented Curriculum (TOC), a major curriculum renewal initiative designed to improve the quality of learning in local primary schools. Discusses the context in which it was introduced and factors that proved problematic in managing change. Focuses on five elements in the change process: practicality, ownership, teacher…

Disadvantaged but Different: Variation among Deprived Communities in Relation to Child and Family Well-Being

ERIC Educational Resources Information Center

Barnes, Jacqueline; Belsky, Jay; Broomfield, Kate A.; Dave, Sapna; Frost, Martin; Melhuish, Edward

2005-01-01

Background: Disadvantaged communities are increasingly the target for interventions. Sure Start was launched in England in 1999 to tackle child poverty and improve child and family services, with Sure Start Local Programmes (SSLPs) targeted at relatively small areas of marked deprivation. However, they are located in a range of different types of…

Modeling the effects of contrast enhancement on target acquisition performance

NASA Astrophysics Data System (ADS)

Du Bosq, Todd W.; Fanning, Jonathan D.

2008-04-01

Contrast enhancement and dynamic range compression are currently being used to improve the performance of infrared imagers by increasing the contrast between the target and the scene content, by better utilizing the available gray levels either globally or locally. This paper assesses the range-performance effects of various contrast enhancement algorithms for target identification with well contrasted vehicles. Human perception experiments were performed to determine field performance using contrast enhancement on the U.S. Army RDECOM CERDEC NVESD standard military eight target set using an un-cooled LWIR camera. The experiments compare the identification performance of observers viewing linearly scaled images and various contrast enhancement processed images. Contrast enhancement is modeled in the US Army thermal target acquisition model (NVThermIP) by changing the scene contrast temperature. The model predicts improved performance based on any improved target contrast, regardless of feature saturation or enhancement. To account for the equivalent blur associated with each contrast enhancement algorithm, an additional effective MTF was calculated and added to the model. The measured results are compared with the predicted performance based on the target task difficulty metric used in NVThermIP.

Effects of non-local electron transport in one-dimensional and two-dimensional simulations of shock-ignited inertial confinement fusion targets

NASA Astrophysics Data System (ADS)

Marocchino, A.; Atzeni, S.; Schiavi, A.

2014-01-01

In some regions of a laser driven inertial fusion target, the electron mean-free path can become comparable to or even longer than the electron temperature gradient scale-length. This can be particularly important in shock-ignited (SI) targets, where the laser-spike heated corona reaches temperatures of several keV. In this case, thermal conduction cannot be described by a simple local conductivity model and a Fick's law. Fluid codes usually employ flux-limited conduction models, which preserve causality, but lose important features of the thermal flow. A more accurate thermal flow modeling requires convolution-like non-local operators. In order to improve the simulation of SI targets, the non-local electron transport operator proposed by Schurtz-Nicolaï-Busquet [G. P. Schurtz et al., Phys. Plasmas 7, 4238 (2000)] has been implemented in the DUED fluid code. Both one-dimensional (1D) and two-dimensional (2D) simulations of SI targets have been performed. 1D simulations of the ablation phase highlight that while the shock profile and timing might be mocked up with a flux-limiter; the electron temperature profiles exhibit a relatively different behavior with no major effects on the final gain. The spike, instead, can only roughly be reproduced with a fixed flux-limiter value. 1D target gain is however unaffected, provided some minor tuning of laser pulses. 2D simulations show that the use of a non-local thermal conduction model does not affect the robustness to mispositioning of targets driven by quasi-uniform laser irradiation. 2D simulations performed with only two final polar intense spikes yield encouraging results and support further studies.

Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers.

PubMed

Feola, Iolanda; Volkers, Linda; Majumder, Rupamanjari; Teplenin, Alexander; Schalij, Martin J; Panfilov, Alexander V; de Vries, Antoine A F; Pijnappels, Daniël A

2017-11-01

Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers. Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca 2+ -translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting). Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation. © 2017 American Heart Association, Inc.

Infrared target recognition based on improved joint local ternary pattern

NASA Astrophysics Data System (ADS)

Sun, Junding; Wu, Xiaosheng

2016-05-01

This paper presents a simple, efficient, yet robust approach, named joint orthogonal combination of local ternary pattern, for automatic forward-looking infrared target recognition. It gives more advantages to describe the macroscopic textures and microscopic textures by fusing variety of scales than the traditional LBP-based methods. In addition, it can effectively reduce the feature dimensionality. Further, the rotation invariant and uniform scheme, the robust LTP, and soft concave-convex partition are introduced to enhance its discriminative power. Experimental results demonstrate that the proposed method can achieve competitive results compared with the state-of-the-art methods.

Nanoparticles that Communicate In Vivo to Amplify Tumour Targeting

PubMed Central

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2012-01-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability for communication to improve targeting in biological systems, such inflammatory cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘Signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally active the coagulation cascade to broadcast tumour location to clot-targeted ‘Receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed from multiple types of Signalling and Receiving modules, can transmit information via multiple molecular pathways in coagulation, can operate autonomously, and can target over 40-fold higher doses of chemotherapeutics to tumours than non-communicating controls. PMID:21685903

Nanoparticles that communicate in vivo to amplify tumour targeting

NASA Astrophysics Data System (ADS)

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2011-07-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted ‘receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed of multiple types of signalling and receiving modules, can transmit information through multiple molecular pathways in coagulation, can operate autonomously and can target over 40 times higher doses of chemotherapeutics to tumours than non-communicating controls.

Drug delivery to the human and mouse uterus using immunoliposomes targeted to the oxytocin receptor.

PubMed

Paul, Jonathan W; Hua, Susan; Ilicic, Marina; Tolosa, Jorge M; Butler, Trent; Robertson, Sarah; Smith, Roger

2017-03-01

The ability to provide safe and effective pharmacotherapy during obstetric complications, such as preterm labor or postpartum hemorrhage, is hampered by the systemic toxicity of therapeutic agents leading to adverse side effects in the mother and fetus. Development of novel strategies to target tocolytic and uterotonic agents specifically to uterine myocytes would improve therapeutic efficacy while minimizing the risk of side effects. Ligand-targeted liposomes have emerged as a reliable and versatile platform for targeted drug delivery to specific cell types, tissues or organs. Our objective was to develop a targeted drug delivery system for the uterus utilizing an immunoliposome platform targeting the oxytocin receptor. We conjugated liposomes to an antibody that recognizes an extracellular domain of the oxytocin receptor. We then examined the ability of oxytocin receptor-targeted liposomes to deliver contraction-blocking (nifedipine, salbutamol and rolipram) or contraction-enhancing (dofetilide) agents to strips of spontaneously contracting myometrial tissue in vitro (human and mouse). We evaluated the ability of oxytocin receptor-targeted liposomes to localize to uterine tissue in vivo, and assessed if targeted liposomes loaded with indomethacin were capable of preventing lipopolysaccharide-induced preterm birth in mice. Oxytocin receptor-targeted liposomes loaded with nifedipine, salbutamol or rolipram consistently abolished human myometrial contractions in vitro, while oxytocin receptor-targeted liposomes loaded with dofetilide increased contraction duration. Nontargeted control liposomes loaded with these agents had no effect. Similar results were observed in mouse uterine strips. Following in vivo administration to pregnant mice, oxytocin receptor-targeted liposomes localized specifically to the uterine horns and mammary tissue. Targeting increased localization to the uterus 7-fold. Localization was not detected in the maternal brain or fetus. Targeted and nontargeted liposomes also localized to the liver. Oxytocin receptor-targeted liposomes loaded with indomethacin were effective in reducing rates of preterm birth in mice, whereas nontargeted liposomes loaded with indomethacin had no effect. Our results demonstrate that oxytocin receptor-targeted liposomes can be used to either inhibit or enhance human uterine contractions in vitro. In vivo, the liposomes localized to the uterine tissue of pregnant mice and were effective in delivering agents for the prevention of inflammation-induced preterm labor. The potential clinical advantage of targeted liposomal drug delivery to the myometrium is reduced dose and reduced toxicity to both mother and fetus. Copyright © 2016. Published by Elsevier Inc.

The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy

NASA Astrophysics Data System (ADS)

Zhao, Mei-Xia; Zhu, Bing-Jie

2016-04-01

Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes.

PubMed

Yu, Nancy Y; Wagner, James R; Laird, Matthew R; Melli, Gabor; Rey, Sébastien; Lo, Raymond; Dao, Phuong; Sahinalp, S Cenk; Ester, Martin; Foster, Leonard J; Brinkman, Fiona S L

2010-07-01

PSORTb has remained the most precise bacterial protein subcellular localization (SCL) predictor since it was first made available in 2003. However, the recall needs to be improved and no accurate SCL predictors yet make predictions for archaea, nor differentiate important localization subcategories, such as proteins targeted to a host cell or bacterial hyperstructures/organelles. Such improvements should preferably be encompassed in a freely available web-based predictor that can also be used as a standalone program. We developed PSORTb version 3.0 with improved recall, higher proteome-scale prediction coverage, and new refined localization subcategories. It is the first SCL predictor specifically geared for all prokaryotes, including archaea and bacteria with atypical membrane/cell wall topologies. It features an improved standalone program, with a new batch results delivery system complementing its web interface. We evaluated the most accurate SCL predictors using 5-fold cross validation plus we performed an independent proteomics analysis, showing that PSORTb 3.0 is the most accurate but can benefit from being complemented by Proteome Analyst predictions. http://www.psort.org/psortb (download open source software or use the web interface). psort-mail@sfu.ca Supplementary data are available at Bioinformatics online.

Targeted therapy for localized non-small-cell lung cancer: a review

PubMed Central

Paleiron, Nicolas; Bylicki, Olivier; André, Michel; Rivière, Emilie; Grassin, Frederic; Robinet, Gilles; Chouaïd, Christos

2016-01-01

Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations) is a major challenge. PMID:27462164

Improved neovascularization and wound repair by targeting human basic fibroblast growth factor (bFGF) to fibrin.

PubMed

Zhao, Wenxue; Han, Qianqian; Lin, Hang; Gao, Yuan; Sun, Wenjie; Zhao, Yannan; Wang, Bin; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu

2008-10-01

Targeted therapy is a new generation of therapeutics, where two critical factors are involved. One is the particular molecular target, and the other is the specific target-binding drug. In this work, the fibrin, a main component of plasma clot at wound sites, was used as the target for human bFGF, aiming to improve therapeutic neovascularization and wound repair. To endow bFGF with fibrin-targeting ability, a fibrin-binding peptide Kringle1 (K1), derived from human plasminogen, was fused to human bFGF. The recombinant K1bFGF showed high fibrin and plasma-clot-binding ability. When applied to the wound sites with plasma clots, K1bFGF induced robust neovascularization and improved wound healing. To extend the application of K1bFGF to other cases where no plasma clots exist, we developed a fibrin-scaffold/K1bFGF system. This system could induce localized neovascularization by delivery of K1bFGF in a sustained and site-targeting manner, and provide a microenvironment promoting cell growth and tissue regeneration. In summary, we successfully used the pathologic environment fibrin clot as the target for bFGF, and based on which bFGF was designed into a targeting agent by introduction of a fibrin-binding peptide. This provides a potential approach to improve therapeutic neovascularization and wound repair.

Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

PubMed

Endo, Takao; Fujikado, Takashi; Hirota, Masakazu; Kanda, Hiroyuki; Morimoto, Takeshi; Nishida, Kohji

2018-04-20

To evaluate the improvement in targeted reaching movements toward targets of various contrasts in a patient implanted with a suprachoroidal-transretinal stimulation (STS) retinal prosthesis. An STS retinal prosthesis was implanted in the right eye of a 42-year-old man with advanced Stargardt disease (visual acuity: right eye, light perception; left eye, hand motion). In localization tests during the 1-year follow-up period, the patient attempted to touch the center of a white square target (visual angle, 10°; contrast, 96, 85, or 74%) displayed at a random position on a monitor. The distance between the touched point and the center of the target (the absolute deviation) was averaged over 20 trials with the STS system on or off. With the left eye occluded, the absolute deviation was not consistently lower with the system on than off for high-contrast (96%) targets, but was consistently lower with the system on for low-contrast (74%) targets. With both eyes open, the absolute deviation was consistently lower with the system on than off for 85%-contrast targets. With the system on and 96%-contrast targets, we detected a shorter response time while covering the right eye, which was being implanted with the STS, compared to covering the left eye (2.41 ± 2.52 vs 8.45 ± 3.78 s, p < 0.01). Performance of a reaching movement improved in a patient with an STS retinal prosthesis implanted in an eye with residual natural vision. Patients with a retinal prosthesis may be able to improve their visual performance by using both artificial vision and their residual natural vision. Beginning date of the trial: Feb. 20, 2014 Date of registration: Jan. 4, 2014 Trial registration number: UMIN000012754 Registration site: UMIN Clinical Trials Registry (UMIN-CTR) http://www.umin.ac.jp/ctr/index.htm.

Example-Based Image Colorization Using Locality Consistent Sparse Representation.

PubMed

Bo Li; Fuchen Zhao; Zhuo Su; Xiangguo Liang; Yu-Kun Lai; Rosin, Paul L

2017-11-01

Image colorization aims to produce a natural looking color image from a given gray-scale image, which remains a challenging problem. In this paper, we propose a novel example-based image colorization method exploiting a new locality consistent sparse representation. Given a single reference color image, our method automatically colorizes the target gray-scale image by sparse pursuit. For efficiency and robustness, our method operates at the superpixel level. We extract low-level intensity features, mid-level texture features, and high-level semantic features for each superpixel, which are then concatenated to form its descriptor. The collection of feature vectors for all the superpixels from the reference image composes the dictionary. We formulate colorization of target superpixels as a dictionary-based sparse reconstruction problem. Inspired by the observation that superpixels with similar spatial location and/or feature representation are likely to match spatially close regions from the reference image, we further introduce a locality promoting regularization term into the energy formulation, which substantially improves the matching consistency and subsequent colorization results. Target superpixels are colorized based on the chrominance information from the dominant reference superpixels. Finally, to further improve coherence while preserving sharpness, we develop a new edge-preserving filter for chrominance channels with the guidance from the target gray-scale image. To the best of our knowledge, this is the first work on sparse pursuit image colorization from single reference images. Experimental results demonstrate that our colorization method outperforms the state-of-the-art methods, both visually and quantitatively using a user study.

Infrared small target detection based on Danger Theory

NASA Astrophysics Data System (ADS)

Lan, Jinhui; Yang, Xiao

2009-11-01

To solve the problem that traditional method can't detect the small objects whose local SNR is less than 2 in IR images, a Danger Theory-based model to detect infrared small target is presented in this paper. First, on the analog with immunology, the definition is given, in this paper, to such terms as dangerous signal, antigens, APC, antibodies. Besides, matching rule between antigen and antibody is improved. Prior to training the detection model and detecting the targets, the IR images are processed utilizing adaptive smooth filter to decrease the stochastic noise. Then at the training process, deleting rule, generating rule, crossover rule and the mutation rule are established after a large number of experiments in order to realize immediate convergence and obtain good antibodies. The Danger Theory-based model is built after the training process, and this model can detect the target whose local SNR is only 1.5.

Two-UAV Intersection Localization System Based on the Airborne Optoelectronic Platform

PubMed Central

Bai, Guanbing; Liu, Jinghong; Song, Yueming; Zuo, Yujia

2017-01-01

To address the limitation of the existing UAV (unmanned aerial vehicles) photoelectric localization method used for moving objects, this paper proposes an improved two-UAV intersection localization system based on airborne optoelectronic platforms by using the crossed-angle localization method of photoelectric theodolites for reference. This paper introduces the makeup and operating principle of intersection localization system, creates auxiliary coordinate systems, transforms the LOS (line of sight, from the UAV to the target) vectors into homogeneous coordinates, and establishes a two-UAV intersection localization model. In this paper, the influence of the positional relationship between UAVs and the target on localization accuracy has been studied in detail to obtain an ideal measuring position and the optimal localization position where the optimal intersection angle is 72.6318°. The result shows that, given the optimal position, the localization root mean square error (RMS) will be 25.0235 m when the target is 5 km away from UAV baselines. Finally, the influence of modified adaptive Kalman filtering on localization results is analyzed, and an appropriate filtering model is established to reduce the localization RMS error to 15.7983 m. Finally, An outfield experiment was carried out and obtained the optimal results: σB=1.63×10−4 (°), σL=1.35×10−4 (°), σH=15.8 (m), σsum=27.6 (m), where σB represents the longitude error, σL represents the latitude error, σH represents the altitude error, and σsum represents the error radius. PMID:28067814

Two-UAV Intersection Localization System Based on the Airborne Optoelectronic Platform.

PubMed

Bai, Guanbing; Liu, Jinghong; Song, Yueming; Zuo, Yujia

2017-01-06

To address the limitation of the existing UAV (unmanned aerial vehicles) photoelectric localization method used for moving objects, this paper proposes an improved two-UAV intersection localization system based on airborne optoelectronic platforms by using the crossed-angle localization method of photoelectric theodolites for reference. This paper introduces the makeup and operating principle of intersection localization system, creates auxiliary coordinate systems, transforms the LOS (line of sight, from the UAV to the target) vectors into homogeneous coordinates, and establishes a two-UAV intersection localization model. In this paper, the influence of the positional relationship between UAVs and the target on localization accuracy has been studied in detail to obtain an ideal measuring position and the optimal localization position where the optimal intersection angle is 72.6318°. The result shows that, given the optimal position, the localization root mean square error (RMS) will be 25.0235 m when the target is 5 km away from UAV baselines. Finally, the influence of modified adaptive Kalman filtering on localization results is analyzed, and an appropriate filtering model is established to reduce the localization RMS error to 15.7983 m. Finally, An outfield experiment was carried out and obtained the optimal results: σ B = 1.63 × 10 - 4 ( ° ) , σ L = 1.35 × 10 - 4 ( ° ) , σ H = 15.8 ( m ) , σ s u m = 27.6 ( m ) , where σ B represents the longitude error, σ L represents the latitude error, σ H represents the altitude error, and σ s u m represents the error radius.

Improving oncoplastic breast tumor bed localization for radiotherapy planning using image registration algorithms

NASA Astrophysics Data System (ADS)

Wodzinski, Marek; Skalski, Andrzej; Ciepiela, Izabela; Kuszewski, Tomasz; Kedzierawski, Piotr; Gajda, Janusz

2018-02-01

Knowledge about tumor bed localization and its shape analysis is a crucial factor for preventing irradiation of healthy tissues during supportive radiotherapy and as a result, cancer recurrence. The localization process is especially hard for tumors placed nearby soft tissues, which undergo complex, nonrigid deformations. Among them, breast cancer can be considered as the most representative example. A natural approach to improving tumor bed localization is the use of image registration algorithms. However, this involves two unusual aspects which are not common in typical medical image registration: the real deformation field is discontinuous, and there is no direct correspondence between the cancer and its bed in the source and the target 3D images respectively. The tumor no longer exists during radiotherapy planning. Therefore, a traditional evaluation approach based on known, smooth deformations and target registration error are not directly applicable. In this work, we propose alternative artificial deformations which model the tumor bed creation process. We perform a comprehensive evaluation of the most commonly used deformable registration algorithms: B-Splines free form deformations (B-Splines FFD), different variants of the Demons and TV-L1 optical flow. The evaluation procedure includes quantitative assessment of the dedicated artificial deformations, target registration error calculation, 3D contour propagation and medical experts visual judgment. The results demonstrate that the currently, practically applied image registration (rigid registration and B-Splines FFD) are not able to correctly reconstruct discontinuous deformation fields. We show that the symmetric Demons provide the most accurate soft tissues alignment in terms of the ability to reconstruct the deformation field, target registration error and relative tumor volume change, while B-Splines FFD and TV-L1 optical flow are not an appropriate choice for the breast tumor bed localization problem, even though the visual alignment seems to be better than for the Demons algorithm. However, no algorithm could recover the deformation field with sufficient accuracy in terms of vector length and rotation angle differences.

PreCisIon: PREdiction of CIS-regulatory elements improved by gene's positION.

PubMed

Elati, Mohamed; Nicolle, Rémy; Junier, Ivan; Fernández, David; Fekih, Rim; Font, Julio; Képès, François

2013-02-01

Conventional approaches to predict transcriptional regulatory interactions usually rely on the definition of a shared motif sequence on the target genes of a transcription factor (TF). These efforts have been frustrated by the limited availability and accuracy of TF binding site motifs, usually represented as position-specific scoring matrices, which may match large numbers of sites and produce an unreliable list of target genes. To improve the prediction of binding sites, we propose to additionally use the unrelated knowledge of the genome layout. Indeed, it has been shown that co-regulated genes tend to be either neighbors or periodically spaced along the whole chromosome. This study demonstrates that respective gene positioning carries significant information. This novel type of information is combined with traditional sequence information by a machine learning algorithm called PreCisIon. To optimize this combination, PreCisIon builds a strong gene target classifier by adaptively combining weak classifiers based on either local binding sequence or global gene position. This strategy generically paves the way to the optimized incorporation of any future advances in gene target prediction based on local sequence, genome layout or on novel criteria. With the current state of the art, PreCisIon consistently improves methods based on sequence information only. This is shown by implementing a cross-validation analysis of the 20 major TFs from two phylogenetically remote model organisms. For Bacillus subtilis and Escherichia coli, respectively, PreCisIon achieves on average an area under the receiver operating characteristic curve of 70 and 60%, a sensitivity of 80 and 70% and a specificity of 60 and 56%. The newly predicted gene targets are demonstrated to be functionally consistent with previously known targets, as assessed by analysis of Gene Ontology enrichment or of the relevant literature and databases.

A review of programs that targeted environmental determinants of Aboriginal and Torres Strait Islander health.

PubMed

Johnston, Leah; Doyle, Joyce; Morgan, Bec; Atkinson-Briggs, Sharon; Firebrace, Bradley; Marika, Mayatili; Reilly, Rachel; Cargo, Margaret; Riley, Therese; Rowley, Kevin

2013-08-09

Effective interventions to improve population and individual health require environmental change as well as strategies that target individual behaviours and clinical factors. This is the basis of implementing an ecological approach to health programs and health promotion. For Aboriginal People and Torres Strait Islanders, colonisation has made the physical and social environment particularly detrimental for health. We conducted a literature review to identify Aboriginal health interventions that targeted environmental determinants of health, identifying 21 different health programs. Program activities that targeted environmental determinants of health included: Caring for Country; changes to food supply and/or policy; infrastructure for physical activity; housing construction and maintenance; anti-smoking policies; increased workforce capacity; continuous quality improvement of clinical systems; petrol substitution; and income management. Targets were categorised according to Miller's Living Systems Theory. Researchers using an Indigenous community based perspective more often identified interpersonal and community-level targets than were identified using a Western academic perspective. Although there are relatively few papers describing interventions that target environmental determinants of health, many of these addressed such determinants at multiple levels, consistent to some degree with an ecological approach. Interpretation of program targets sometimes differed between academic and community-based perspectives, and was limited by the type of data reported in the journal articles, highlighting the need for local Indigenous knowledge for accurate program evaluation. While an ecological approach to Indigenous health is increasingly evident in the health research literature, the design and evaluation of such programs requires a wide breadth of expertise, including local Indigenous knowledge.

A Review of Programs That Targeted Environmental Determinants of Aboriginal and Torres Strait Islander Health

PubMed Central

Johnston, Leah; Doyle, Joyce; Morgan, Bec; Atkinson-Briggs, Sharon; Firebrace, Bradley; Marika, Mayatili; Reilly, Rachel; Cargo, Margaret; Riley, Therese; Rowley, Kevin

2013-01-01

Objective: Effective interventions to improve population and individual health require environmental change as well as strategies that target individual behaviours and clinical factors. This is the basis of implementing an ecological approach to health programs and health promotion. For Aboriginal People and Torres Strait Islanders, colonisation has made the physical and social environment particularly detrimental for health. Methods and Results: We conducted a literature review to identify Aboriginal health interventions that targeted environmental determinants of health, identifying 21 different health programs. Program activities that targeted environmental determinants of health included: Caring for Country; changes to food supply and/or policy; infrastructure for physical activity; housing construction and maintenance; anti-smoking policies; increased workforce capacity; continuous quality improvement of clinical systems; petrol substitution; and income management. Targets were categorised according to Miller’s Living Systems Theory. Researchers using an Indigenous community based perspective more often identified interpersonal and community-level targets than were identified using a Western academic perspective. Conclusions: Although there are relatively few papers describing interventions that target environmental determinants of health, many of these addressed such determinants at multiple levels, consistent to some degree with an ecological approach. Interpretation of program targets sometimes differed between academic and community-based perspectives, and was limited by the type of data reported in the journal articles, highlighting the need for local Indigenous knowledge for accurate program evaluation. Implications: While an ecological approach to Indigenous health is increasingly evident in the health research literature, the design and evaluation of such programs requires a wide breadth of expertise, including local Indigenous knowledge. PMID:23939388

Practical ways to facilitate ergonomics improvements in occupational health practice.

PubMed

Kogi, Kazutaka

2012-12-01

Recent advances in participatory programs for improving workplace conditions are discussed to examine practical ways to facilitate ergonomics improvements. Participatory training programs are gaining importance, particularly in promoting occupational health and safety in small-scale workplaces. These programs have led to many improvements that can reduce work-related risks in varied situations. Recent experiences in participatory action-oriented training programs in small workplaces and agriculture are reviewed.The emphasis of the review is on training steps, types of improvements achieved, and the use of action tools by trainers and training participants. Immediate improvements in multiple technical areas are targeted, including materials handling,workstation design, physical environment, welfare facilities, and work organization. In facilitating ergonomics improvements in each local situation, it is important to focus on (a) building on local good practices; (b) applying practical, simple improvements that apply the basic principles of ergonomics; and (c) developing action-oriented toolkits for direct use by workers and managers. This facilitation process is effective when locally designed action toolkits are used by trainers, including local good examples, action checklists, and illustrated how-to guides. Intervention studies demonstrate the effectiveness of participatory steps that use these toolkits in promoting good practices and reducing work-related risks. In facilitating ergonomics improvements in small-scale workplaces, it is important to focus on practical, low-cost improvements that build on local good practices. The use of action-oriented toolkits reflecting basic ergonomics principles is helpful.The promotion of the intercountry networking of positive experiences in participatory training is suggested.

Ultrasound guided fluorescence molecular tomography with improved quantification by an attenuation compensated born-normalization and in vivo preclinical study of cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Baoqiang; Berti, Romain; Abran, Maxime

2014-05-15

Ultrasound imaging, having the advantages of low-cost and non-invasiveness over MRI and X-ray CT, was reported by several studies as an adequate complement to fluorescence molecular tomography with the perspective of improving localization and quantification of fluorescent molecular targets in vivo. Based on the previous work, an improved dual-modality Fluorescence-Ultrasound imaging system was developed and then validated in imaging study with preclinical tumor model. Ultrasound imaging and a profilometer were used to obtain the anatomical prior information and 3D surface, separately, to precisely extract the tissue boundary on both sides of sample in order to achieve improved fluorescence reconstruction. Furthermore,more » a pattern-based fluorescence reconstruction on the detection side was incorporated to enable dimensional reduction of the dataset while keeping the useful information for reconstruction. Due to its putative role in the current imaging geometry and the chosen reconstruction technique, we developed an attenuation compensated Born-normalization method to reduce the attenuation effects and cancel off experimental factors when collecting quantitative fluorescence datasets over large area. Results of both simulation and phantom study demonstrated that fluorescent targets could be recovered accurately and quantitatively using this reconstruction mechanism. Finally, in vivo experiment confirms that the imaging system associated with the proposed image reconstruction approach was able to extract both functional and anatomical information, thereby improving quantification and localization of molecular targets.« less

State and Local Implementation of the No Child Left Behind Act. Volume VI--Targeting and Uses of Federal Education Funds

ERIC Educational Resources Information Center

Chambers, Jay G.; Lam, Irene; Mahitivanichcha, Kanya; Esra, Phil; Shambaugh, Larisa; Stullich, Stephanie

2009-01-01

Achieving the goals of federal education legislation depends on how federal funds are distributed and used. Since the enactment of the Elementary and Secondary Education Act (ESEA) in 1965, various federal programs have been created to support educational improvement and target additional resources to meet the educational needs of children who are…

Highlights of Fire in the United States: Deaths, Injuries, Dollar Loss, and Incidents at the National, State, and Local Levels.

ERIC Educational Resources Information Center

National Fire Prevention and Control Administration (DOC), Washington, DC. National Fire Data Center.

This report provides fire departments, federal and state governments, and others active in the fire protection field with information which can be used to improve the efficacy and targeting of fire prevention programs. As a byproduct, it illustrates ways that state and local governments might analyze their own fire problems. The report describes…

Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.

PubMed

Hua, Susan; Marks, Ellen; Schneider, Jennifer J; Keely, Simon

2015-07-01

Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Prostate Bed Motion During Intensity-Modulated Radiotherapy Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klayton, Tracy; Price, Robert; Buyyounouski, Mark K.

Purpose: Conformal radiation therapy in the postprostatectomy setting requires accurate setup and localization of the prostatic fossa. In this series, we report prostate bed localization and motion characteristics, using data collected from implanted radiofrequency transponders. Methods and Materials: The Calypso four-dimensional localization system uses three implanted radiofrequency transponders for daily target localization and real-time tracking throughout a course of radiation therapy. We reviewed the localization and tracking reports for 20 patients who received ultrasonography-guided placement of Calypso transponders within the prostate bed prior to a course of intensity-modulated radiation therapy at Fox Chase Cancer Center. Results: At localization, prostate bedmore » displacement relative to bony anatomy exceeded 5 mm in 9% of fractions in the anterior-posterior (A-P) direction and 21% of fractions in the superior-inferior (S-I) direction. The three-dimensional vector length from skin marks to Calypso alignment exceeded 1 cm in 24% of all 652 fractions with available setup data. During treatment, the target exceeded the 5-mm tracking limit for at least 30 sec in 11% of all fractions, generally in the A-P or S-I direction. In the A-P direction, target motion was twice as likely to move posteriorly, toward the rectum, than anteriorly. Fifteen percent of all treatments were interrupted for repositioning, and 70% of patients were repositioned at least once during their treatment course. Conclusion: Set-up errors and motion of the prostatic fossa during radiotherapy are nontrivial, leading to potential undertreatment of target and excess normal tissue toxicity if not taken into account during treatment planning. Localization and real-time tracking of the prostate bed via implanted Calypso transponders can be used to improve the accuracy of plan delivery.« less

The Geography of Diabetes in London, Canada: The Need for Local Level Policy for Prevention and Management

PubMed Central

Tompkins, Jordan W.; Luginaah, Isaac N.; Booth, Gillian L.; Harris, Stewart B.

2010-01-01

Recent reports aimed at improving diabetes care in socially disadvantaged populations suggest that interventions must be tailored to meet the unique needs of the local community—specifically, the community’s geography. We have examined the spatial distribution of diabetes in the context of socioeconomic determinants of health in London (Ontario, Canada) to characterize neighbourhoods in an effort to target these neighbourhoods for local level community-based program planning and intervention. Multivariate spatial-statistical techniques and geographic information systems were used to examine diabetes rates and socioeconomic variables aggregated at the census tract level. Creation of a deprivation index facilitated investigation across multiple determinants of health. Findings from our research identified ‘at risk’ neighbourhoods in London with socioeconomic disadvantage and high diabetes. Future endeavours must continue to identify local level trends in order to support policy development, resource planning and care for improved health outcomes and improved equity in access to care across geographic regions. PMID:20623032

A bio-inspired swarm robot coordination algorithm for multiple target searching

NASA Astrophysics Data System (ADS)

Meng, Yan; Gan, Jing; Desai, Sachi

2008-04-01

The coordination of a multi-robot system searching for multi targets is challenging under dynamic environment since the multi-robot system demands group coherence (agents need to have the incentive to work together faithfully) and group competence (agents need to know how to work together well). In our previous proposed bio-inspired coordination method, Local Interaction through Virtual Stigmergy (LIVS), one problem is the considerable randomness of the robot movement during coordination, which may lead to more power consumption and longer searching time. To address these issues, an adaptive LIVS (ALIVS) method is proposed in this paper, which not only considers the travel cost and target weight, but also predicting the target/robot ratio and potential robot redundancy with respect to the detected targets. Furthermore, a dynamic weight adjustment is also applied to improve the searching performance. This new method a truly distributed method where each robot makes its own decision based on its local sensing information and the information from its neighbors. Basically, each robot only communicates with its neighbors through a virtual stigmergy mechanism and makes its local movement decision based on a Particle Swarm Optimization (PSO) algorithm. The proposed ALIVS algorithm has been implemented on the embodied robot simulator, Player/Stage, in a searching target. The simulation results demonstrate the efficiency and robustness in a power-efficient manner with the real-world constraints.

Evaluation of intensified image enhancement through conspicuity and triangle orientation discrimination measures

NASA Astrophysics Data System (ADS)

Dijk, Judith; van Eekeren, Adam W. M.; Toet, Alexander; den Hollander, Richard J. M.; Schutte, Klamer; van Heijningen, Ad W. P.; Bijl, Piet

2013-04-01

For many military operations, situational awareness is of great importance. During night conditions, this situational awareness can be improved using both analog and digital image-intensified cameras. The quality of image intensifiers is a topic of interest. One of the differences between a digital and analog system is noise behavior. For digital image intensifiers, the noise behavior is not as good as for analog image intensifiers, but it can be improved using noise-reduction techniques. In this paper, the improvement using temporal noise reduction and local adaptive contrast enhancement is shown and quantitatively evaluated by subjective measurement of the conspicuity and triangle orientation discrimination (TOD). The results of the conspicuity and TOD experiments are consistent with each other. The highest improvement is found for a low-clutter environment; for medium- and high-clutter environments, the improvement is less. This can be explained by the fact that image enhancement increases contrast of all image details, irrespective of whether they are targets or clutter. For low-clutter image enhancement, target conspicuity and target detection improvement will be largest, since there are not many distracting elements.

Exploiting domain information for Word Sense Disambiguation of medical documents.

PubMed

Stevenson, Mark; Agirre, Eneko; Soroa, Aitor

2012-01-01

Current techniques for knowledge-based Word Sense Disambiguation (WSD) of ambiguous biomedical terms rely on relations in the Unified Medical Language System Metathesaurus but do not take into account the domain of the target documents. The authors' goal is to improve these methods by using information about the topic of the document in which the ambiguous term appears. The authors proposed and implemented several methods to extract lists of key terms associated with Medical Subject Heading terms. These key terms are used to represent the document topic in a knowledge-based WSD system. They are applied both alone and in combination with local context. A standard measure of accuracy was calculated over the set of target words in the widely used National Library of Medicine WSD dataset. The authors report a significant improvement when combining those key terms with local context, showing that domain information improves the results of a WSD system based on the Unified Medical Language System Metathesaurus alone. The best results were obtained using key terms obtained by relevance feedback and weighted by inverse document frequency.

Exploiting domain information for Word Sense Disambiguation of medical documents

PubMed Central

Agirre, Eneko; Soroa, Aitor

2011-01-01

Objective Current techniques for knowledge-based Word Sense Disambiguation (WSD) of ambiguous biomedical terms rely on relations in the Unified Medical Language System Metathesaurus but do not take into account the domain of the target documents. The authors' goal is to improve these methods by using information about the topic of the document in which the ambiguous term appears. Design The authors proposed and implemented several methods to extract lists of key terms associated with Medical Subject Heading terms. These key terms are used to represent the document topic in a knowledge-based WSD system. They are applied both alone and in combination with local context. Measurements A standard measure of accuracy was calculated over the set of target words in the widely used National Library of Medicine WSD dataset. Results and discussion The authors report a significant improvement when combining those key terms with local context, showing that domain information improves the results of a WSD system based on the Unified Medical Language System Metathesaurus alone. The best results were obtained using key terms obtained by relevance feedback and weighted by inverse document frequency. PMID:21900701

Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks' gestation: the AVIOx study.

PubMed

Hagadorn, James I; Furey, Anne M; Nghiem, Tuyet-Hang; Schmid, Christopher H; Phelps, Dale L; Pillers, De-Ann M; Cole, Cynthia H

2006-10-01

The objective of this study was to document pulse oximeter saturation levels achieved in the first 4 weeks of life in infants who were born at < 28 weeks' gestation, compared with the levels that were targeted by local policy, and examine factors that are associated with compliance with the target range. Infants who were < 28 weeks' gestation and < or = 96 hours of age were enrolled in a prospective, multicenter cohort study. Oximetry data were collected with masked signal-extraction oximeters for a 72-hour period in each of the first 4 weeks of life. Data were compared with the pulse oximeter saturation target range prescribed by local institutional policy. Factors that were associated with intended range compliance were identified with hierarchical modeling. Fourteen centers from 3 countries enrolled 84 infants with mean +/- SD birth weight of 863 +/- 208 g and gestational age of 26 +/- 1.4 weeks. Oxygen saturation policy limits ranged between 83% and 92% for lower limits and 92% and 98% for upper limits. For infants who received respiratory support, median pulse oximeter saturation level achieved was 95%. Center-specific medial levels were within the intended range at 12 centers. Centers maintained infants within their intended range 16% to 64% of the time but were above range 20% to 73% of the time. In hierarchical modeling, wider target ranges, higher target range upper limits, presence of a policy of setting oximeter alarms close to the target range limits, and lower gestational age were associated with improved target range compliance. Success with maintaining the intended pulse oximeter saturation range varied substantially among centers, among patients within centers, and for individual patients over time. Most noncompliance was above the intended range. Methods for improving compliance and the effect of improved compliance on neonatal outcomes require additional research.

Improving health visitor emollient prescribing using a CQUIN-based approach.

PubMed

Brooks, Christina; Khatau, Tejas

2015-12-01

Prescribing is an essential element of health visiting practice. This initiative used the payment framework of Commissioning for Quality and Innovation (CQUIN) to develop health visiting practice across a large health visiting workforce in the East Midlands. A focus on emollient prescribing practice was agreed and a guidance booklet regarding preferred emollient products was produced, based on the local formulary Each health visitor benefitted from receiving additional training and was given a guidance booklet to inform their practice. Targets were set for each quarter to demonstrate an improved prescribing adherence to the preferred product list.The targets were achieved for each quarter. Prescribing rates and confidence improved across the service. Therefore, it was demonstrated that specific guidance and ongoing support can improve prescribing practice within the health visiting service.

Distributed Peer-to-Peer Target Tracking in Wireless Sensor Networks

PubMed Central

Wang, Xue; Wang, Sheng; Bi, Dao-Wei; Ma, Jun-Jie

2007-01-01

Target tracking is usually a challenging application for wireless sensor networks (WSNs) because it is always computation-intensive and requires real-time processing. This paper proposes a practical target tracking system based on the auto regressive moving average (ARMA) model in a distributed peer-to-peer (P2P) signal processing framework. In the proposed framework, wireless sensor nodes act as peers that perform target detection, feature extraction, classification and tracking, whereas target localization requires the collaboration between wireless sensor nodes for improving the accuracy and robustness. For carrying out target tracking under the constraints imposed by the limited capabilities of the wireless sensor nodes, some practically feasible algorithms, such as the ARMA model and the 2-D integer lifting wavelet transform, are adopted in single wireless sensor nodes due to their outstanding performance and light computational burden. Furthermore, a progressive multi-view localization algorithm is proposed in distributed P2P signal processing framework considering the tradeoff between the accuracy and energy consumption. Finally, a real world target tracking experiment is illustrated. Results from experimental implementations have demonstrated that the proposed target tracking system based on a distributed P2P signal processing framework can make efficient use of scarce energy and communication resources and achieve target tracking successfully.

Reducing emergency bed-days for older people? Network governance lessons from the 'Improving the Future for Older People' programme.

PubMed

Sheaff, Rod; Windle, Karen; Wistow, Gerald; Ashby, Sue; Beech, Roger; Dickinson, Angela; Henderson, Catherine; Knapp, Martin

2014-04-01

In 2007, the UK government set performance targets and public service agreements to control the escalation of emergency bed-days. Some years earlier, nine English local authorities had each created local networks with their health and third sector partners to tackle this increase. These networks formed the 'Improving the Future for Older People' initiative (IFOP), one strand of the national 'Innovation Forum' programme, set up in 2003. The nine sites set themselves one headline target to be achieved jointly over three years; a 20 per cent reduction in the number of emergency bed-days used by people aged 75 and over. Three ancillary targets were also monitored: emergency admissions, delayed discharges and project sustainability. Collectively the sites exceeded their headline target. Using a realistic evaluation approach, we explored which aspects of network governance appeared to have contributed to these emergency bed-day reductions. We found no simple link between network governance type and outcomes. The governance features associated with an effective IFOP network appeared to suggest that the selection and implementation of a small number of evidence-based services was central to networks' effectiveness. Each service needed to be coordinated by a network-based strategic group and hierarchically implemented at operational level by the responsible network member. Having a network-based implementation group with a 'joined-at-the-top' governance structure also appeared to promote network effectiveness. External factors, including NHS incentives, health reorganisations and financial targets similarly contributed to differences in performance. Targets and financial incentives could focus action but undermine horizontal networking. Local networks should specify which interventions network structures are intended to deliver. Effective projects are those likely to be evidence based, unique to the network and difficult to implement through vertical structures alone. Copyright © 2014 Elsevier Ltd. All rights reserved.

Percutaneous radiofrequency facet capsule denervation as an alternative target in lumbar facet syndrome.

PubMed

Moussa, Wael Mohamed Mohamed; Khedr, Wael

2016-11-01

Percutaneous radiofrequency denervation of the medial dorsal branch is often used in chronic low back pain of intervertebral facet etiology, which is sometimes difficult to perform and recurrence of pain often ensues. We theorized that shifting the target of RF coagulation to the facet joint capsule would provide an easier target and a longer-lived pain relieving response. A prospective randomized controlled trial where 120 patients diagnosed with CLBP of a confirmed facet origin were randomly divided into three equal groups, the first was submitted to percutaneous radiofrequency coagulation of the facet joint capsule, the second underwent percuataneous denervation of the medial dorsal branch and the third did not receive radiofrequency lesioning. All the three groups received local injection of a mixture of local anesthetic and steroid. Cases were followed for up to 3 years. 87(72.5%) patients were females. By 3 months' post procedure, improvement in VAS was significantly better than pretreatment levels in all groups (p<0.05). The control group lost improvement by 1-year follow-up (p=0.017). At 2 years' follow-up, the joint capsule denervation group maintained significant improvement (p=0.033) whereas the medial branch denervation group lost its significant effect (p=0.479). By the end of follow-up period, only joint capsule denervation group kept significant improvement (p=0.026). In CLBP of facet origin, shifting the target of percutaneous radiofrequency to the facet joint capsule provides an easier technique with an extended period of pain relief compared to the medial dorsal branch of the facet joint. Copyright © 2016 Elsevier B.V. All rights reserved.

Priority interventions to improve maternal and child diets in Sub-Saharan Africa and South Asia.

PubMed

Masters, William A; Rosettie, Katherine; Kranz, Sarah; Pedersen, Sarah H; Webb, Patrick; Danaei, Goodarz; Mozaffarian, Dariush

2018-04-01

Nutrition-sensitive interventions to improve overall diet quality are increasingly needed to improve maternal and child health. This study demonstrates feasibility of a structured process to leverage local expertise in formulating programmes tailored for current circumstances in South Asia and Africa. We assembled 41 stakeholders in 2 regional workshops and followed a prespecified protocol to elicit programme designs listing the human and other resources required, the intervention's mechanism for impact on diets, target foods and nutrients, target populations, and contact information for partners needed to implement the desired programme. Via this protocol, participants described 48 distinct interventions, which we then compared against international recommendations and global goals. Local stakeholders' priorities focused on postharvest food systems to improve access to nutrient-dense products (75% of the 48 programmes) and on production of animal sourced foods (58%), as well as education and social marketing (23%) and direct transfers to meet food needs (12.5%). Each programme included an average of 3.2 distinct elements aligned with those recommended by United Nations system agencies in the Framework for Action produced by the Second International Conference on Nutrition in 2014 and the Compendium of Actions for Nutrition developed for the Renewed Efforts Against Child Hunger initiative in 2016. Our results demonstrate that a participatory process can help local experts identify their own priorities for future investments, as a first step in a novel process of rigorous, transparent, and independent priority setting to improve diets among those at greatest risk of undernutrition. © 2017 The Authors. Maternal and Child Nutrition published by John Wiley & Sons, Ltd.

Priority interventions to improve maternal and child diets in Sub‐Saharan Africa and South Asia

PubMed Central

Masters, William A.; Rosettie, Katherine; Kranz, Sarah; Pedersen, Sarah H.; Webb, Patrick; Danaei, Goodarz; Adekugbe, Olayinka; Adhikar, Ramesh Kant; Amatya, Archana; Atomsa, Gudina Egata; Badham, Jane; Bhattacharjee, Lalita; Bhattarai, Manav; Baye, Kaleab; Beyero, Mesfin; Brahmbhatt, Viral; Chandrasekhar, S.; Chandyo, Ram Krishna; Christensen, Cheryl; Covic, Namukolo; Dalton, Babukiika; Desai, Sonalde; Dufour, Charlotte; Fracassi, Patrizia; Getahun, Zewditu; Gulati, Seema; Haidar, Jemal; Hailu, Tesfaye; Kapil, Umesh; Kazi‐Hutchins, Nabeeha; Kebede, Aweke; Kinabo, Joyce; Kussaga, Jamal Bakari; Levin, Carol; Mavrotas, George; Mehta, Ranju; Mohan, Sailesh; Mwanja, Wilson Waiswa; Oguntona, Babatunde; Oladipo, Abiodun; Oniang'o, Ruth; Paarlberg, Robert; Pandey Rana, Pooja; Prabhakaran, D.; Prakash, V.; Puri, Seema; Roy, S. K.; Sharma, Rekha; Shivakoti, Sabnam; Sibanda, Simbarashe; Sodjinou, Roger; Thorne‐Lyman, Andrew; Tom, Carol; Trilok‐Kumar, Geeta; Vosti, Steven; Wamani, Henry; Wendelin, Akwilina

2017-01-01

Abstract Nutrition‐sensitive interventions to improve overall diet quality are increasingly needed to improve maternal and child health. This study demonstrates feasibility of a structured process to leverage local expertise in formulating programmes tailored for current circumstances in South Asia and Africa. We assembled 41 stakeholders in 2 regional workshops and followed a prespecified protocol to elicit programme designs listing the human and other resources required, the intervention's mechanism for impact on diets, target foods and nutrients, target populations, and contact information for partners needed to implement the desired programme. Via this protocol, participants described 48 distinct interventions, which we then compared against international recommendations and global goals. Local stakeholders' priorities focused on postharvest food systems to improve access to nutrient‐dense products (75% of the 48 programmes) and on production of animal sourced foods (58%), as well as education and social marketing (23%) and direct transfers to meet food needs (12.5%). Each programme included an average of 3.2 distinct elements aligned with those recommended by United Nations system agencies in the Framework for Action produced by the Second International Conference on Nutrition in 2014 and the Compendium of Actions for Nutrition developed for the Renewed Efforts Against Child Hunger initiative in 2016. Our results demonstrate that a participatory process can help local experts identify their own priorities for future investments, as a first step in a novel process of rigorous, transparent, and independent priority setting to improve diets among those at greatest risk of undernutrition. PMID:28971572

Modified linear predictive coding approach for moving target tracking by Doppler radar

NASA Astrophysics Data System (ADS)

Ding, Yipeng; Lin, Xiaoyi; Sun, Ke-Hui; Xu, Xue-Mei; Liu, Xi-Yao

2016-07-01

Doppler radar is a cost-effective tool for moving target tracking, which can support a large range of civilian and military applications. A modified linear predictive coding (LPC) approach is proposed to increase the target localization accuracy of the Doppler radar. Based on the time-frequency analysis of the received echo, the proposed approach first real-time estimates the noise statistical parameters and constructs an adaptive filter to intelligently suppress the noise interference. Then, a linear predictive model is applied to extend the available data, which can help improve the resolution of the target localization result. Compared with the traditional LPC method, which empirically decides the extension data length, the proposed approach develops an error array to evaluate the prediction accuracy and thus, adjust the optimum extension data length intelligently. Finally, the prediction error array is superimposed with the predictor output to correct the prediction error. A series of experiments are conducted to illustrate the validity and performance of the proposed techniques.

Voluntary control of intracortical oscillations for reconfiguration of network activity

PubMed Central

Corlier, Juliana; Valderrama, Mario; Navarrete, Miguel; Lehongre, Katia; Hasboun, Dominique; Adam, Claude; Belaid, Hayat; Clémenceau, Stéphane; Baulac, Michel; Charpier, Stéphane; Navarro, Vincent; Le Van Quyen, Michel

2016-01-01

Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition. PMID:27808225

Deformable registration of the inflated and deflated lung in cone-beam CT-guided thoracic surgery: Initial investigation of a combined model- and image-driven approach

PubMed Central

Uneri, Ali; Nithiananthan, Sajendra; Schafer, Sebastian; Otake, Yoshito; Stayman, J. Webster; Kleinszig, Gerhard; Sussman, Marc S.; Prince, Jerry L.; Siewerdsen, Jeffrey H.

2013-01-01

Purpose: Surgical resection is the preferred modality for curative treatment of early stage lung cancer, but localization of small tumors (<10 mm diameter) during surgery presents a major challenge that is likely to increase as more early-stage disease is detected incidentally and in low-dose CT screening. To overcome the difficulty of manual localization (fingers inserted through intercostal ports) and the cost, logistics, and morbidity of preoperative tagging (coil or dye placement under CT-fluoroscopy), the authors propose the use of intraoperative cone-beam CT (CBCT) and deformable image registration to guide targeting of small tumors in video-assisted thoracic surgery (VATS). A novel algorithm is reported for registration of the lung from its inflated state (prior to pleural breach) to the deflated state (during resection) to localize surgical targets and adjacent critical anatomy. Methods: The registration approach geometrically resolves images of the inflated and deflated lung using a coarse model-driven stage followed by a finer image-driven stage. The model-driven stage uses image features derived from the lung surfaces and airways: triangular surface meshes are morphed to capture bulk motion; concurrently, the airways generate graph structures from which corresponding nodes are identified. Interpolation of the sparse motion fields computed from the bounding surface and interior airways provides a 3D motion field that coarsely registers the lung and initializes the subsequent image-driven stage. The image-driven stage employs an intensity-corrected, symmetric form of the Demons method. The algorithm was validated over 12 datasets, obtained from porcine specimen experiments emulating CBCT-guided VATS. Geometric accuracy was quantified in terms of target registration error (TRE) in anatomical targets throughout the lung, and normalized cross-correlation. Variations of the algorithm were investigated to study the behavior of the model- and image-driven stages by modifying individual algorithmic steps and examining the effect in comparison to the nominal process. Results: The combined model- and image-driven registration process demonstrated accuracy consistent with the requirements of minimally invasive VATS in both target localization (∼3–5 mm within the target wedge) and critical structure avoidance (∼1–2 mm). The model-driven stage initialized the registration to within a median TRE of 1.9 mm (95% confidence interval (CI) maximum = 5.0 mm), while the subsequent image-driven stage yielded higher accuracy localization with 0.6 mm median TRE (95% CI maximum = 4.1 mm). The variations assessing the individual algorithmic steps elucidated the role of each step and in some cases identified opportunities for further simplification and improvement in computational speed. Conclusions: The initial studies show the proposed registration method to successfully register CBCT images of the inflated and deflated lung. Accuracy appears sufficient to localize the target and adjacent critical anatomy within ∼1–2 mm and guide localization under conditions in which the target cannot be discerned directly in CBCT (e.g., subtle, nonsolid tumors). The ability to directly localize tumors in the operating room could provide a valuable addition to the VATS arsenal, obviate the cost, logistics, and morbidity of preoperative tagging, and improve patient safety. Future work includes in vivo testing, optimization of workflow, and integration with a CBCT image guidance system. PMID:23298134

Deformable registration of the inflated and deflated lung in cone-beam CT-guided thoracic surgery: initial investigation of a combined model- and image-driven approach.

PubMed

Uneri, Ali; Nithiananthan, Sajendra; Schafer, Sebastian; Otake, Yoshito; Stayman, J Webster; Kleinszig, Gerhard; Sussman, Marc S; Prince, Jerry L; Siewerdsen, Jeffrey H

2013-01-01

Surgical resection is the preferred modality for curative treatment of early stage lung cancer, but localization of small tumors (<10 mm diameter) during surgery presents a major challenge that is likely to increase as more early-stage disease is detected incidentally and in low-dose CT screening. To overcome the difficulty of manual localization (fingers inserted through intercostal ports) and the cost, logistics, and morbidity of preoperative tagging (coil or dye placement under CT-fluoroscopy), the authors propose the use of intraoperative cone-beam CT (CBCT) and deformable image registration to guide targeting of small tumors in video-assisted thoracic surgery (VATS). A novel algorithm is reported for registration of the lung from its inflated state (prior to pleural breach) to the deflated state (during resection) to localize surgical targets and adjacent critical anatomy. The registration approach geometrically resolves images of the inflated and deflated lung using a coarse model-driven stage followed by a finer image-driven stage. The model-driven stage uses image features derived from the lung surfaces and airways: triangular surface meshes are morphed to capture bulk motion; concurrently, the airways generate graph structures from which corresponding nodes are identified. Interpolation of the sparse motion fields computed from the bounding surface and interior airways provides a 3D motion field that coarsely registers the lung and initializes the subsequent image-driven stage. The image-driven stage employs an intensity-corrected, symmetric form of the Demons method. The algorithm was validated over 12 datasets, obtained from porcine specimen experiments emulating CBCT-guided VATS. Geometric accuracy was quantified in terms of target registration error (TRE) in anatomical targets throughout the lung, and normalized cross-correlation. Variations of the algorithm were investigated to study the behavior of the model- and image-driven stages by modifying individual algorithmic steps and examining the effect in comparison to the nominal process. The combined model- and image-driven registration process demonstrated accuracy consistent with the requirements of minimally invasive VATS in both target localization (∼3-5 mm within the target wedge) and critical structure avoidance (∼1-2 mm). The model-driven stage initialized the registration to within a median TRE of 1.9 mm (95% confidence interval (CI) maximum = 5.0 mm), while the subsequent image-driven stage yielded higher accuracy localization with 0.6 mm median TRE (95% CI maximum = 4.1 mm). The variations assessing the individual algorithmic steps elucidated the role of each step and in some cases identified opportunities for further simplification and improvement in computational speed. The initial studies show the proposed registration method to successfully register CBCT images of the inflated and deflated lung. Accuracy appears sufficient to localize the target and adjacent critical anatomy within ∼1-2 mm and guide localization under conditions in which the target cannot be discerned directly in CBCT (e.g., subtle, nonsolid tumors). The ability to directly localize tumors in the operating room could provide a valuable addition to the VATS arsenal, obviate the cost, logistics, and morbidity of preoperative tagging, and improve patient safety. Future work includes in vivo testing, optimization of workflow, and integration with a CBCT image guidance system.

Ocean Ambient Noise Studies for Improved Sonar Processing

DTIC Science & Technology

2013-09-30

conceptual basis of using multipath arrivals to enhance target localization still holds promise. In this project, the emphasis is on analytically and...Nosal 2006] E. Nosal and L. Neilfrazer, "Track of a sperm whale from delays between direct and surface-reflected clicks," Applied Acoustics, vol. 67, no...V. O’Connell, and K. Folkert, “Three- dimensional localization of sperm whales using a single hydrophone”, J. Acous. Soc. Am. 120, 2355-2365 (2006

Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction.

PubMed

Zhang, Li; Sun, Zhenxing; Ren, Pingping; You, Manjie; Zhang, Jing; Fang, Lingyun; Wang, Jing; Chen, Yihan; Yan, Fei; Zheng, Hairong; Xie, Mingxing

2017-01-01

Hypoxia-inducible factor 1α (HIF-1α) plays a critical protective role in ischemic heart disease. Under normoxic conditions, HIF-1α was degraded by oxygen-dependent prolyl hydroxylase-2 (PHD2). Gene therapy has become a promising strategy to inhibit the degradation of HIF-1α and to improve cardiac function after ischemic injury. However, conventional gene delivery systems are difficult to achieve a targeted and localized gene delivery into the ischemic myocardia. Here, we report the localized myocardial delivery of shRNA against PHD2 through ultrasound-targeted microbubble destruction (UTMD) for protection the heart from acute myocardial infarction. In this study, a novel cationic microbubble was fabricated by using of the thin-film hydration and sonication method. The resulting microbubbles had a 28.2 ± 2.21 mV surface zeta potential and could greatly improve DNA binding performance, achieving 17.81 ± 1.46 μg of DNA loading capacity per 5 × 10 8 microbubbles. Combined with these cationic microbubbles, UTMD-mediated gene delivery was evaluated and the gene transfection efficiency was optimized in the H9C2 cardiac cells. Knockdown of PHD2 gene was successfully realized by UTMD-mediated shPHD2 transfection, resulting in HIF-1α-dependent protective effects on H9C2 cells through increasing the expression of HIF-1α, VEGF and bFGF. We further employed UTMD-mediated shPHD2 transfection into the localized ischemic myocardia in a rat ischemia model, demonstrating significantly reduced infarct size and greatly improved the heart function. The silencing of PHD2 and the up-regulation of its downstream genes in the treated myocardia were confirmed. Histological analysis further revealed numbers of HIF-1α- and VEGF-, and CD31-positive cells/mm 2 in the shPHD2-treated group were significantly greater than those in the sham or control vector groups (P < 0.05). In conclusion, our study provides a promising strategy to realize ultrasound-mediated localized myocardial shRNA delivery to protect the heart from acute myocardial infarction via cationic microbubbles.

Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction

PubMed Central

Zhang, Li; Sun, Zhenxing; Ren, Pingping; You, Manjie; Zhang, Jing; Fang, Lingyun; Wang, Jing; Chen, Yihan; Yan, Fei; Zheng, Hairong; Xie, Mingxing

2017-01-01

Hypoxia-inducible factor 1α (HIF-1α) plays a critical protective role in ischemic heart disease. Under normoxic conditions, HIF-1α was degraded by oxygen-dependent prolyl hydroxylase-2 (PHD2). Gene therapy has become a promising strategy to inhibit the degradation of HIF-1α and to improve cardiac function after ischemic injury. However, conventional gene delivery systems are difficult to achieve a targeted and localized gene delivery into the ischemic myocardia. Here, we report the localized myocardial delivery of shRNA against PHD2 through ultrasound-targeted microbubble destruction (UTMD) for protection the heart from acute myocardial infarction. In this study, a novel cationic microbubble was fabricated by using of the thin-film hydration and sonication method. The resulting microbubbles had a 28.2 ± 2.21 mV surface zeta potential and could greatly improve DNA binding performance, achieving 17.81 ± 1.46 μg of DNA loading capacity per 5 × 108 microbubbles. Combined with these cationic microbubbles, UTMD-mediated gene delivery was evaluated and the gene transfection efficiency was optimized in the H9C2 cardiac cells. Knockdown of PHD2 gene was successfully realized by UTMD-mediated shPHD2 transfection, resulting in HIF-1α-dependent protective effects on H9C2 cells through increasing the expression of HIF-1α, VEGF and bFGF. We further employed UTMD-mediated shPHD2 transfection into the localized ischemic myocardia in a rat ischemia model, demonstrating significantly reduced infarct size and greatly improved the heart function. The silencing of PHD2 and the up-regulation of its downstream genes in the treated myocardia were confirmed. Histological analysis further revealed numbers of HIF-1α- and VEGF-, and CD31-positive cells/mm2 in the shPHD2-treated group were significantly greater than those in the sham or control vector groups (P < 0.05). In conclusion, our study provides a promising strategy to realize ultrasound-mediated localized myocardial shRNA delivery to protect the heart from acute myocardial infarction via cationic microbubbles. PMID:28042316

Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

PubMed Central

Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

2016-01-01

Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

MRI-Guided Focused Ultrasound as a New Method of Drug Delivery

PubMed Central

Thanou, M.; Gedroyc, W.

2013-01-01

Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery. PMID:23738076

Detection of Multiple Stationary Humans Using UWB MIMO Radar.

PubMed

Liang, Fulai; Qi, Fugui; An, Qiang; Lv, Hao; Chen, Fuming; Li, Zhao; Wang, Jianqi

2016-11-16

Remarkable progress has been achieved in the detection of single stationary human. However, restricted by the mutual interference of multiple humans (e.g., strong sidelobes of the torsos and the shadow effect), detection and localization of the multiple stationary humans remains a huge challenge. In this paper, ultra-wideband (UWB) multiple-input and multiple-output (MIMO) radar is exploited to improve the detection performance of multiple stationary humans for its multiple sight angles and high-resolution two-dimensional imaging capacity. A signal model of the vital sign considering both bi-static angles and attitude angle of the human body is firstly developed, and then a novel detection method is proposed to detect and localize multiple stationary humans. In this method, preprocessing is firstly implemented to improve the signal-to-noise ratio (SNR) of the vital signs, and then a vital-sign-enhanced imaging algorithm is presented to suppress the environmental clutters and mutual affection of multiple humans. Finally, an automatic detection algorithm including constant false alarm rate (CFAR), morphological filtering and clustering is implemented to improve the detection performance of weak human targets affected by heavy clutters and shadow effect. The simulation and experimental results show that the proposed method can get a high-quality image of multiple humans and we can use it to discriminate and localize multiple adjacent human targets behind brick walls.

Detection of Multiple Stationary Humans Using UWB MIMO Radar

PubMed Central

Liang, Fulai; Qi, Fugui; An, Qiang; Lv, Hao; Chen, Fuming; Li, Zhao; Wang, Jianqi

2016-01-01

Remarkable progress has been achieved in the detection of single stationary human. However, restricted by the mutual interference of multiple humans (e.g., strong sidelobes of the torsos and the shadow effect), detection and localization of the multiple stationary humans remains a huge challenge. In this paper, ultra-wideband (UWB) multiple-input and multiple-output (MIMO) radar is exploited to improve the detection performance of multiple stationary humans for its multiple sight angles and high-resolution two-dimensional imaging capacity. A signal model of the vital sign considering both bi-static angles and attitude angle of the human body is firstly developed, and then a novel detection method is proposed to detect and localize multiple stationary humans. In this method, preprocessing is firstly implemented to improve the signal-to-noise ratio (SNR) of the vital signs, and then a vital-sign-enhanced imaging algorithm is presented to suppress the environmental clutters and mutual affection of multiple humans. Finally, an automatic detection algorithm including constant false alarm rate (CFAR), morphological filtering and clustering is implemented to improve the detection performance of weak human targets affected by heavy clutters and shadow effect. The simulation and experimental results show that the proposed method can get a high-quality image of multiple humans and we can use it to discriminate and localize multiple adjacent human targets behind brick walls. PMID:27854356

Electromagnetic induction and radiation-induced abnormality of wave propagation in excitable media

NASA Astrophysics Data System (ADS)

Ma, Jun; Wu, Fuqiang; Hayat, Tasawar; Zhou, Ping; Tang, Jun

2017-11-01

Continuous wave emitting from sinus node of the heart plays an important role in wave propagating among cardiac tissue, while the heart beating can be terminated when the target wave is broken into turbulent states by electromagnetic radiation. In this investigation, local periodical forcing is applied on the media to induce continuous target wave in the improved cardiac model, which the effect of electromagnetic induction is considered by using magnetic flux, then external electromagnetic radiation is imposed on the media. It is found that target wave propagation can be blocked to stand in a local area and the excitability of media is suppressed to approach quiescent but homogeneous state when electromagnetic radiation is imposed on the media. The sampled time series for membrane potentials decrease to quiescent state due to the electromagnetic radiation. It could accounts for the mechanism of abnormality in heart failure exposed to continuous electromagnetic field.

Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

PubMed

Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

2016-12-01

Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

Adoption and Design of Emerging Dietary Policies to Improve Cardiometabolic Health in the US.

PubMed

Huang, Yue; Pomeranz, Jennifer; Wilde, Parke; Capewell, Simon; Gaziano, Tom; O'Flaherty, Martin; Kersh, Rogan; Whitsel, Laurie; Mozaffarian, Dariush; Micha, Renata

2018-04-14

Suboptimal diet is a leading cause of cardiometabolic disease and economic burdens. Evidence-based dietary policies within 5 domains-food prices, reformulation, marketing, labeling, and government food assistance programs-appear promising at improving cardiometabolic health. Yet, the extent of new dietary policy adoption in the US and key elements crucial to define in designing such policies are not well established. We created an inventory of recent US dietary policy cases aiming to improve cardiometabolic health and assessed the extent of their proposal and adoption at federal, state, local, and tribal levels; and categorized and characterized the key elements in their policy design. Recent federal dietary policies adopted to improve cardiometabolic health include reformulation (trans-fat elimination), marketing (mass-media campaigns to increase fruits and vegetables), labeling (Nutrition Facts Panel updates, menu calorie labeling), and food assistance programs (financial incentives for fruits and vegetables in the Supplemental Nutrition Assistance Program (SNAP) and Women, Infant and Children (WIC) program). Federal voluntary guidelines have been proposed for sodium reformulation and food marketing to children. Recent state proposals included sugar-sweetened beverage (SSB) taxes, marketing restrictions, and SNAP restrictions, but few were enacted. Local efforts varied significantly, with certain localities consistently leading in the proposal or adoption of relevant policies. Across all jurisdictions, most commonly selected dietary targets included fruits and vegetables, SSBs, trans-fat, added sugar, sodium, and calories; other healthy (e.g., nuts) or unhealthy (e.g., processed meats) factors were largely not addressed. Key policy elements to define in designing these policies included those common across domains (e.g., level of government, target population, dietary target, dietary definition, implementation mechanism), and domain-specific (e.g., media channels for food marketing domain) or policy-specific (e.g., earmarking for taxes) elements. Characteristics of certain elements were similarly defined (e.g., fruit and vegetable definition, warning language used in SSB warning labels), while others varied across cases within a policy (e.g., tax base for SSB taxes). Several key elements were not always sufficiently characterized in government documents, and dietary target selections and definitions did not consistently align with the evidence-base. These findings highlight recent action on dietary policies to improve cardiometabolic health in the US; and key elements necessary to design such policies.

Accounting for spatially heterogeneous conditions in local-scale surveillance strategies: case study of the biosecurity insect pest, grape phylloxera (Daktulosphaira vitifoliae (Fitch)).

PubMed

Triska, Maggie D; Powell, Kevin S; Collins, Cassandra; Pearce, Inca; Renton, Michael

2018-04-29

Surveillance strategies are often standardized and completed on grid patterns to detect pest incursions quickly; however, it may be possible to improve surveillance through more targeted surveillance that accounts for landscape heterogeneity, dispersal and the habitat requirements of the invading organism. We simulated pest spread at a local-scale, using grape phylloxera (Daktulosphaira vitifoliae (Fitch)) as a case study, and assessed the influence of incorporating spatial heterogeneity into surveillance strategies compared to current, standard surveillance strategies. Time to detection, spread within and spread beyond the vineyard were reduced by conducting surveys that target sampling effort in soil that is highly suitable to the invading pest in comparison to standard surveillance strategies. However, these outcomes were dependent on the virulence level of phylloxera as phylloxera is a complex pest with multiple genotypes that influence spread and detectability. Targeting surveillance strategies based on local-scale spatial heterogeneity can decrease the time to detection without increasing the survey cost and surveillance that targets highly suitable soil is the most efficient strategy for detecting new incursions. Additionally, combining targeted surveillance strategies with buffer zones and hygiene procedures, and updating surveillance strategies as additional species information becomes available, will further decrease the risk of pest spread. This article is protected by copyright. All rights reserved.

The new approach for infrared target tracking based on the particle filter algorithm

NASA Astrophysics Data System (ADS)

Sun, Hang; Han, Hong-xia

2011-08-01

Target tracking on the complex background in the infrared image sequence is hot research field. It provides the important basis in some fields such as video monitoring, precision, and video compression human-computer interaction. As a typical algorithms in the target tracking framework based on filtering and data connection, the particle filter with non-parameter estimation characteristic have ability to deal with nonlinear and non-Gaussian problems so it were widely used. There are various forms of density in the particle filter algorithm to make it valid when target occlusion occurred or recover tracking back from failure in track procedure, but in order to capture the change of the state space, it need a certain amount of particles to ensure samples is enough, and this number will increase in accompany with dimension and increase exponentially, this led to the increased amount of calculation is presented. In this paper particle filter algorithm and the Mean shift will be combined. Aiming at deficiencies of the classic mean shift Tracking algorithm easily trapped into local minima and Unable to get global optimal under the complex background. From these two perspectives that "adaptive multiple information fusion" and "with particle filter framework combining", we expand the classic Mean Shift tracking framework .Based on the previous perspective, we proposed an improved Mean Shift infrared target tracking algorithm based on multiple information fusion. In the analysis of the infrared characteristics of target basis, Algorithm firstly extracted target gray and edge character and Proposed to guide the above two characteristics by the moving of the target information thus we can get new sports guide grayscale characteristics and motion guide border feature. Then proposes a new adaptive fusion mechanism, used these two new information adaptive to integrate into the Mean Shift tracking framework. Finally we designed a kind of automatic target model updating strategy to further improve tracking performance. Experimental results show that this algorithm can compensate shortcoming of the particle filter has too much computation, and can effectively overcome the fault that mean shift is easy to fall into local extreme value instead of global maximum value .Last because of the gray and fusion target motion information, this approach also inhibit interference from the background, ultimately improve the stability and the real-time of the target track.

Approach to explosive hazard detection using sensor fusion and multiple kernel learning with downward-looking GPR and EMI sensor data

NASA Astrophysics Data System (ADS)

Pinar, Anthony; Masarik, Matthew; Havens, Timothy C.; Burns, Joseph; Thelen, Brian; Becker, John

2015-05-01

This paper explores the effectiveness of an anomaly detection algorithm for downward-looking ground penetrating radar (GPR) and electromagnetic inductance (EMI) data. Threat detection with GPR is challenged by high responses to non-target/clutter objects, leading to a large number of false alarms (FAs), and since the responses of target and clutter signatures are so similar, classifier design is not trivial. We suggest a method based on a Run Packing (RP) algorithm to fuse GPR and EMI data into a composite confidence map to improve detection as measured by the area-under-ROC (NAUC) metric. We examine the value of a multiple kernel learning (MKL) support vector machine (SVM) classifier using image features such as histogram of oriented gradients (HOG), local binary patterns (LBP), and local statistics. Experimental results on government furnished data show that use of our proposed fusion and classification methods improves the NAUC when compared with the results from individual sensors and a single kernel SVM classifier.

A Dependable Localization Algorithm for Survivable Belt-Type Sensor Networks.

PubMed

Zhu, Mingqiang; Song, Fei; Xu, Lei; Seo, Jung Taek; You, Ilsun

2017-11-29

As the key element, sensor networks are widely investigated by the Internet of Things (IoT) community. When massive numbers of devices are well connected, malicious attackers may deliberately propagate fake position information to confuse the ordinary users and lower the network survivability in belt-type situation. However, most existing positioning solutions only focus on the algorithm accuracy and do not consider any security aspects. In this paper, we propose a comprehensive scheme for node localization protection, which aims to improve the energy-efficient, reliability and accuracy. To handle the unbalanced resource consumption, a node deployment mechanism is presented to satisfy the energy balancing strategy in resource-constrained scenarios. According to cooperation localization theory and network connection property, the parameter estimation model is established. To achieve reliable estimations and eliminate large errors, an improved localization algorithm is created based on modified average hop distances. In order to further improve the algorithms, the node positioning accuracy is enhanced by using the steepest descent method. The experimental simulations illustrate the performance of new scheme can meet the previous targets. The results also demonstrate that it improves the belt-type sensor networks' survivability, in terms of anti-interference, network energy saving, etc.

A Dependable Localization Algorithm for Survivable Belt-Type Sensor Networks

PubMed Central

Zhu, Mingqiang; Song, Fei; Xu, Lei; Seo, Jung Taek

2017-01-01

As the key element, sensor networks are widely investigated by the Internet of Things (IoT) community. When massive numbers of devices are well connected, malicious attackers may deliberately propagate fake position information to confuse the ordinary users and lower the network survivability in belt-type situation. However, most existing positioning solutions only focus on the algorithm accuracy and do not consider any security aspects. In this paper, we propose a comprehensive scheme for node localization protection, which aims to improve the energy-efficient, reliability and accuracy. To handle the unbalanced resource consumption, a node deployment mechanism is presented to satisfy the energy balancing strategy in resource-constrained scenarios. According to cooperation localization theory and network connection property, the parameter estimation model is established. To achieve reliable estimations and eliminate large errors, an improved localization algorithm is created based on modified average hop distances. In order to further improve the algorithms, the node positioning accuracy is enhanced by using the steepest descent method. The experimental simulations illustrate the performance of new scheme can meet the previous targets. The results also demonstrate that it improves the belt-type sensor networks’ survivability, in terms of anti-interference, network energy saving, etc. PMID:29186072

Quantification of non-coding RNA target localization diversity and its application in cancers.

PubMed

Cheng, Lixin; Leung, Kwong-Sak

2018-04-01

Subcellular localization is pivotal for RNAs and proteins to implement biological functions. The localization diversity of protein interactions has been studied as a crucial feature of proteins, considering that the protein-protein interactions take place in various subcellular locations. Nevertheless, the localization diversity of non-coding RNA (ncRNA) target proteins has not been systematically studied, especially its characteristics in cancers. In this study, we provide a new algorithm, non-coding RNA target localization coefficient (ncTALENT), to quantify the target localization diversity of ncRNAs based on the ncRNA-protein interaction and protein subcellular localization data. ncTALENT can be used to calculate the target localization coefficient of ncRNAs and measure how diversely their targets are distributed among the subcellular locations in various scenarios. We focus our study on long non-coding RNAs (lncRNAs), and our observations reveal that the target localization diversity is a primary characteristic of lncRNAs in different biotypes. Moreover, we found that lncRNAs in multiple cancers, differentially expressed cancer lncRNAs, and lncRNAs with multiple cancer target proteins are prone to have high target localization diversity. Furthermore, the analysis of gastric cancer helps us to obtain a better understanding that the target localization diversity of lncRNAs is an important feature closely related to clinical prognosis. Overall, we systematically studied the target localization diversity of the lncRNAs and uncovered its association with cancer.

Locality-constrained anomaly detection for hyperspectral imagery

NASA Astrophysics Data System (ADS)

Liu, Jiabin; Li, Wei; Du, Qian; Liu, Kui

2015-12-01

Detecting a target with low-occurrence-probability from unknown background in a hyperspectral image, namely anomaly detection, is of practical significance. Reed-Xiaoli (RX) algorithm is considered as a classic anomaly detector, which calculates the Mahalanobis distance between local background and the pixel under test. Local RX, as an adaptive RX detector, employs a dual-window strategy to consider pixels within the frame between inner and outer windows as local background. However, the detector is sensitive if such a local region contains anomalous pixels (i.e., outliers). In this paper, a locality-constrained anomaly detector is proposed to remove outliers in the local background region before employing the RX algorithm. Specifically, a local linear representation is designed to exploit the internal relationship between linearly correlated pixels in the local background region and the pixel under test and its neighbors. Experimental results demonstrate that the proposed detector improves the original local RX algorithm.

State-building at the Community Level: Evaluating the Impact of Colombia’s Consolidation Program

DTIC Science & Technology

2017-10-31

municipalities. 2 These indicator covered mea ure of govemm nt phy ical control, as well as local bureaucratic capacity, social and economic integration...with the re t of Colombia, and local economic conditions. Outcomes were organized along three key dimensions of tate-building from both scholarly...territory (phy ical economic , and political). The P CRT reflected an effort to improve the GoC aero all of these dimensions in the targeted

Magnetic STAR technology for real-time localization and classification of unexploded ordnance and buried mines

NASA Astrophysics Data System (ADS)

Wiegert, R. F.

2009-05-01

A man-portable Magnetic Scalar Triangulation and Ranging ("MagSTAR") technology for Detection, Localization and Classification (DLC) of unexploded ordnance (UXO) has been developed by Naval Surface Warfare Center Panama City Division (NSWC PCD) with support from the Strategic Environmental Research and Development Program (SERDP). Proof of principle of the MagSTAR concept and its unique advantages for real-time, high-mobility magnetic sensing applications have been demonstrated by field tests of a prototype man-portable MagSTAR sensor. The prototype comprises: a) An array of fluxgate magnetometers configured as a multi-tensor gradiometer, b) A GPS-synchronized signal processing system. c) Unique STAR algorithms for point-by-point, standoff DLC of magnetic targets. This paper outlines details of: i) MagSTAR theory, ii) Design and construction of the prototype sensor, iii) Signal processing algorithms recently developed to improve the technology's target-discrimination accuracy, iv) Results of field tests of the portable gradiometer system against magnetic dipole targets. The results demonstrate that the MagSTAR technology is capable of very accurate, high-speed localization of magnetic targets at standoff distances of several meters. These advantages could readily be transitioned to a wide range of defense, security and sensing applications to provide faster and more effective DLC of UXO and buried mines.

150 {mu}A 18F{sup -} target and beam port upgrade for the IBA 18/9 cyclotron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stokely, M. H.; Peeples, J. L.; Poorman, M. C.

2012-12-19

A high power ({approx}3 kW) target platform has been developed for the IBA 18/9 cyclotron. New designs for the airlock, collimator and target subsystems have been fabricated and deployed. The primary project goal is reliable commercial production of 18F{sup -} at 150 {mu}A or greater, while secondary goals include improving serviceability and extending service intervals relative to OEM systems. Reliable operation in a production environment has been observed at beam currents up to 140 {mu}A. Challenges include ion source lifetime and localized peaking in the beam intensity distribution.

Magnetic nanoparticle-based approaches to locally target therapy and enhance tissue regeneration in vivo.

PubMed

Sensenig, Richard; Sapir, Yulia; MacDonald, Cristin; Cohen, Smadar; Polyak, Boris

2012-09-01

Magnetic-based systems utilizing superparamagnetic nanoparticles and a magnetic field gradient to exert a force on these particles have been used in a wide range of biomedical applications. This review is focused on drug targeting applications that require penetration of a cellular barrier as well as strategies to improve the efficacy of targeting in these biomedical applications. Another focus of this review is regenerative applications utilizing tissue engineered scaffolds prepared with the aid of magnetic particles, the use of remote actuation for release of bioactive molecules and magneto-mechanical cell stimulation, cell seeding and cell patterning.

Cooperative tumour cell membrane targeted phototherapy

NASA Astrophysics Data System (ADS)

Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

2017-06-01

The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Pretesh R., E-mail: patel073@mc.duke.edu; Yoo, Sua; Broadwater, Gloria

Purpose: To assess the impact of increasing experience with intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). Methods and Materials: The records of all patients who received IMRT following EPP at Duke University Medical Center between 2005 and 2010 were reviewed. Target volumes included the preoperative extent of the pleural space, chest wall incisions, involved nodal stations, and a boost to close/positive surgical margins if applicable. Patients were typically treated with 9-11 beams with gantry angles, collimator rotations, and beam apertures manually fixed to avoid the contalateral lung and to optimize target coverage. Toxicity wasmore » graded retrospectively using National Cancer Institute common toxicity criteria version 4.0. Target coverage and contralateral lung irradiation were evaluated over time by using linear regression. Local control, disease-free survival, and overall survival rates were estimated using the Kaplan-Meier method. Results: Thirty patients received IMRT following EPP; 21 patients also received systemic chemotherapy. Median follow-up was 15 months. The median dose prescribed to the entire ipsilateral hemithorax was 45 Gy (range, 40-50.4 Gy) with a boost of 8-25 Gy in 9 patients. Median survival was 23.2 months. Two-year local control, disease-free survival, and overall survival rates were 47%, 34%, and 50%, respectively. Increasing experience planning MPM cases was associated with improved coverage of planning target volumes (P=.04). Similarly, mean lung dose (P<.01) and lung V5 (volume receiving 5 Gy or more; P<.01) values decreased with increasing experience. Lung toxicity developed after IMRT in 4 (13%) patients at a median of 2.2 months after RT (three grade 3-4 and one grade 5). Lung toxicity developed in 4 of the initial 15 patients vs none of the last 15 patients treated. Conclusions: With increasing experience, target volume coverage improved and dose to the contralateral lung decreased. Rates of pulmonary toxicity were relatively low. However, both local and distant control rates remained suboptimal.« less

Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars.

PubMed

Cavanagh, Colin R; Chao, Shiaoman; Wang, Shichen; Huang, Bevan Emma; Stephen, Stuart; Kiani, Seifollah; Forrest, Kerrie; Saintenac, Cyrille; Brown-Guedira, Gina L; Akhunova, Alina; See, Deven; Bai, Guihua; Pumphrey, Michael; Tomar, Luxmi; Wong, Debbie; Kong, Stephan; Reynolds, Matthew; da Silva, Marta Lopez; Bockelman, Harold; Talbert, Luther; Anderson, James A; Dreisigacker, Susanne; Baenziger, Stephen; Carter, Arron; Korzun, Viktor; Morrell, Peter Laurent; Dubcovsky, Jorge; Morell, Matthew K; Sorrells, Mark E; Hayden, Matthew J; Akhunov, Eduard

2013-05-14

Domesticated crops experience strong human-mediated selection aimed at developing high-yielding varieties adapted to local conditions. To detect regions of the wheat genome subject to selection during improvement, we developed a high-throughput array to interrogate 9,000 gene-associated single-nucleotide polymorphisms (SNP) in a worldwide sample of 2,994 accessions of hexaploid wheat including landraces and modern cultivars. Using a SNP-based diversity map we characterized the impact of crop improvement on genomic and geographic patterns of genetic diversity. We found evidence of a small population bottleneck and extensive use of ancestral variation often traceable to founders of cultivars from diverse geographic regions. Analyzing genetic differentiation among populations and the extent of haplotype sharing, we identified allelic variants subjected to selection during improvement. Selective sweeps were found around genes involved in the regulation of flowering time and phenology. An introgression of a wild relative-derived gene conferring resistance to a fungal pathogen was detected by haplotype-based analysis. Comparing selective sweeps identified in different populations, we show that selection likely acts on distinct targets or multiple functionally equivalent alleles in different portions of the geographic range of wheat. The majority of the selected alleles were present at low frequency in local populations, suggesting either weak selection pressure or temporal variation in the targets of directional selection during breeding probably associated with changing agricultural practices or environmental conditions. The developed SNP chip and map of genetic variation provide a resource for advancing wheat breeding and supporting future population genomic and genome-wide association studies in wheat.

Genome-wide comparative diversity uncovers multiple targets of selection for improvement in hexaploid wheat landraces and cultivars

PubMed Central

Cavanagh, Colin R.; Chao, Shiaoman; Wang, Shichen; Huang, Bevan Emma; Stephen, Stuart; Kiani, Seifollah; Forrest, Kerrie; Saintenac, Cyrille; Brown-Guedira, Gina L.; Akhunova, Alina; See, Deven; Bai, Guihua; Pumphrey, Michael; Tomar, Luxmi; Wong, Debbie; Kong, Stephan; Reynolds, Matthew; da Silva, Marta Lopez; Bockelman, Harold; Talbert, Luther; Anderson, James A.; Dreisigacker, Susanne; Baenziger, Stephen; Carter, Arron; Korzun, Viktor; Morrell, Peter Laurent; Dubcovsky, Jorge; Morell, Matthew K.; Sorrells, Mark E.; Hayden, Matthew J.; Akhunov, Eduard

2013-01-01

Domesticated crops experience strong human-mediated selection aimed at developing high-yielding varieties adapted to local conditions. To detect regions of the wheat genome subject to selection during improvement, we developed a high-throughput array to interrogate 9,000 gene-associated single-nucleotide polymorphisms (SNP) in a worldwide sample of 2,994 accessions of hexaploid wheat including landraces and modern cultivars. Using a SNP-based diversity map we characterized the impact of crop improvement on genomic and geographic patterns of genetic diversity. We found evidence of a small population bottleneck and extensive use of ancestral variation often traceable to founders of cultivars from diverse geographic regions. Analyzing genetic differentiation among populations and the extent of haplotype sharing, we identified allelic variants subjected to selection during improvement. Selective sweeps were found around genes involved in the regulation of flowering time and phenology. An introgression of a wild relative-derived gene conferring resistance to a fungal pathogen was detected by haplotype-based analysis. Comparing selective sweeps identified in different populations, we show that selection likely acts on distinct targets or multiple functionally equivalent alleles in different portions of the geographic range of wheat. The majority of the selected alleles were present at low frequency in local populations, suggesting either weak selection pressure or temporal variation in the targets of directional selection during breeding probably associated with changing agricultural practices or environmental conditions. The developed SNP chip and map of genetic variation provide a resource for advancing wheat breeding and supporting future population genomic and genome-wide association studies in wheat. PMID:23630259

Occlusion handling framework for tracking in smart camera networks by per-target assistance task assignment

NASA Astrophysics Data System (ADS)

Bo, Nyan Bo; Deboeverie, Francis; Veelaert, Peter; Philips, Wilfried

2017-09-01

Occlusion is one of the most difficult challenges in the area of visual tracking. We propose an occlusion handling framework to improve the performance of local tracking in a smart camera view in a multicamera network. We formulate an extensible energy function to quantify the quality of a camera's observation of a particular target by taking into account both person-person and object-person occlusion. Using this energy function, a smart camera assesses the quality of observations over all targets being tracked. When it cannot adequately observe of a target, a smart camera estimates the quality of observation of the target from view points of other assisting cameras. If a camera with better observation of the target is found, the tracking task of the target is carried out with the assistance of that camera. In our framework, only positions of persons being tracked are exchanged between smart cameras. Thus, communication bandwidth requirement is very low. Performance evaluation of our method on challenging video sequences with frequent and severe occlusions shows that the accuracy of a baseline tracker is considerably improved. We also report the performance comparison to the state-of-the-art trackers in which our method outperforms.

Plant microRNA-Target Interaction Identification Model Based on the Integration of Prediction Tools and Support Vector Machine

PubMed Central

Meng, Jun; Shi, Lin; Luan, Yushi

2014-01-01

Background Confident identification of microRNA-target interactions is significant for studying the function of microRNA (miRNA). Although some computational miRNA target prediction methods have been proposed for plants, results of various methods tend to be inconsistent and usually lead to more false positive. To address these issues, we developed an integrated model for identifying plant miRNA–target interactions. Results Three online miRNA target prediction toolkits and machine learning algorithms were integrated to identify and analyze Arabidopsis thaliana miRNA-target interactions. Principle component analysis (PCA) feature extraction and self-training technology were introduced to improve the performance. Results showed that the proposed model outperformed the previously existing methods. The results were validated by using degradome sequencing supported Arabidopsis thaliana miRNA-target interactions. The proposed model constructed on Arabidopsis thaliana was run over Oryza sativa and Vitis vinifera to demonstrate that our model is effective for other plant species. Conclusions The integrated model of online predictors and local PCA-SVM classifier gained credible and high quality miRNA-target interactions. The supervised learning algorithm of PCA-SVM classifier was employed in plant miRNA target identification for the first time. Its performance can be substantially improved if more experimentally proved training samples are provided. PMID:25051153

Gene Therapy Targeting Glaucoma: Where Are We?

PubMed Central

Liu, Xuyang; Rasmussen, Carol A.; Gabelt, B’Ann T.; Brandt, Curtis R.; Kaufman, Paul L.

2010-01-01

In a chronic disease such as glaucoma, a therapy that provides a long lasting local effect, with minimal systemic side effects, while circumventing the issue of patient compliance, is very attractive. The field of gene therapy is growing rapidly and ocular applications are expanding. Our understanding of the molecular pathogenesis of glaucoma is leading to greater specificity in ocular tissue targeting. Improvements in gene delivery techniques, refinement of vector construction methods, and development of better animal models combine to bring this potential therapy closer to reality. PMID:19539835

Exploring a National Book-Gifting Scheme: Parents' and Children's Reactions

ERIC Educational Resources Information Center

Wray, David; Medwell, Jane

2015-01-01

Several early learning programmes have targeted children's reading, particularly their relationships with books. One, Bookstart, provided free books to babies attending their eighth-month health check at local clinics. Study of this programme suggested that it led to an improvement in language performance upon school entry. Booktime continues from…

Prediction of pesticide acute toxicity using two-dimensional chemical descriptors and target species classification

EPA Science Inventory

Previous modelling of the median lethal dose (oral rat LD50) has indicated that local class-based models yield better correlations than global models. We evaluated the hypothesis that dividing the dataset by pesticidal mechanisms would improve prediction accuracy. A linear discri...

Navigating School Safety Law and Policy

ERIC Educational Resources Information Center

Vaillancourt, Kelly; Rossen, Eric

2012-01-01

Initiatives designed to improve school safety and conditions for learning have become central to education reform efforts at the local, state, and national levels. These efforts often target the reduction and prevention of bullying, discrimination, and harassment in schools. While most states currently have some form of law or policy designed to…

An Update on Modern Approaches to Localized Esophageal Cancer

PubMed Central

Welsh, James; Amini, Arya; Likhacheva, Anna; Erasmus, Jeremy; Gomez, Daniel; Davila, Marta; Mehran, Reza J; Komaki, Ritsuko; Liao, Zhongxing; Hofstetter, Wayne L; Bhutani, Manoop; Ajani, Jaffer A

2014-01-01

Esophageal cancer treatment continues to be a topic of wide debate. Based on improvements in chemotherapy drugs, surgical techniques, and radiotherapy advances, esophageal cancer treatment approaches are becoming more specific to the stage of the tumor and the overall performance status of the patient. While surgery continues to be the standard treatment option for localized disease, the current direction favors multimodality treatment including both radiation and chemotherapy with surgery. In the next few years, we will continue to see improvements in radiation techniques and proton treatment, with more minimally invasive surgical approaches minimizing postoperative side effects, and the discovery of molecular biomarkers to help deliver more specifically targeted medication to treat esophageal cancers. PMID:21365188

Image guided radiation therapy may result in improved local control in locally advanced lung cancer patients.

PubMed

Kilburn, Jeremy M; Soike, Michael H; Lucas, John T; Ayala-Peacock, Diandra; Blackstock, William; Isom, Scott; Kearns, William T; Hinson, William H; Miller, Antonius A; Petty, William J; Munley, Michael T; Urbanic, James J

2016-01-01

Image guided radiation therapy (IGRT) is designed to ensure accurate and precise targeting, but whether improved clinical outcomes result is unknown. A retrospective comparison of locally advanced lung cancer patients treated with and without IGRT from 2001 to 2012 was conducted. Median local failure-free survival (LFFS), regional, locoregional failure-free survival (LRFFS), distant failure-free survival, progression-free survival, and overall survival (OS) were estimated. Univariate and multivariate models assessed the association between patient- and treatment-related covariates and local failure. A total of 169 patients were treated with definitive radiation therapy and concurrent chemotherapy with a median follow-up of 48 months in the IGRT cohort and 96 months in the non-IGRT cohort. IGRT was used in 36% (62 patients) of patients. OS was similar between cohorts (2-year OS, 47% vs 49%, P = .63). The IGRT cohort had improved 2-year LFFS (80% vs 64%, P = .013) and LRFFS (75% and 62%, P = .04). Univariate analysis revealed IGRT and treatment year improved LFFS, whereas group stage, dose, and positron emission tomography/computed tomography planning had no impact. IGRT remained significant in the multivariate model with an adjusted hazard ratio of 0.40 (P = .01). Distant failure-free survival (58% vs 59%, P = .67) did not differ significantly. IGRT with daily cone beam computed tomography confers an improvement in the therapeutic ratio relative to patients treated without this technology. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

An Accurate and Fault-Tolerant Target Positioning System for Buildings Using Laser Rangefinders and Low-Cost MEMS-Based MARG Sensors

PubMed Central

Zhao, Lin; Guan, Dongxue; Landry, René Jr.; Cheng, Jianhua; Sydorenko, Kostyantyn

2015-01-01

Target positioning systems based on MEMS gyros and laser rangefinders (LRs) have extensive prospects due to their advantages of low cost, small size and easy realization. The target positioning accuracy is mainly determined by the LR’s attitude derived by the gyros. However, the attitude error is large due to the inherent noises from isolated MEMS gyros. In this paper, both accelerometer/magnetometer and LR attitude aiding systems are introduced to aid MEMS gyros. A no-reset Federated Kalman Filter (FKF) is employed, which consists of two local Kalman Filters (KF) and a Master Filter (MF). The local KFs are designed by using the Direction Cosine Matrix (DCM)-based dynamic equations and the measurements from the two aiding systems. The KFs can estimate the attitude simultaneously to limit the attitude errors resulting from the gyros. Then, the MF fuses the redundant attitude estimates to yield globally optimal estimates. Simulation and experimental results demonstrate that the FKF-based system can improve the target positioning accuracy effectively and allow for good fault-tolerant capability. PMID:26512672

A Hybrid Search Algorithm for Swarm Robots Searching in an Unknown Environment

PubMed Central

Li, Shoutao; Li, Lina; Lee, Gordon; Zhang, Hao

2014-01-01

This paper proposes a novel method to improve the efficiency of a swarm of robots searching in an unknown environment. The approach focuses on the process of feeding and individual coordination characteristics inspired by the foraging behavior in nature. A predatory strategy was used for searching; hence, this hybrid approach integrated a random search technique with a dynamic particle swarm optimization (DPSO) search algorithm. If a search robot could not find any target information, it used a random search algorithm for a global search. If the robot found any target information in a region, the DPSO search algorithm was used for a local search. This particle swarm optimization search algorithm is dynamic as all the parameters in the algorithm are refreshed synchronously through a communication mechanism until the robots find the target position, after which, the robots fall back to a random searching mode. Thus, in this searching strategy, the robots alternated between two searching algorithms until the whole area was covered. During the searching process, the robots used a local communication mechanism to share map information and DPSO parameters to reduce the communication burden and overcome hardware limitations. If the search area is very large, search efficiency may be greatly reduced if only one robot searches an entire region given the limited resources available and time constraints. In this research we divided the entire search area into several subregions, selected a target utility function to determine which subregion should be initially searched and thereby reduced the residence time of the target to improve search efficiency. PMID:25386855

A hybrid search algorithm for swarm robots searching in an unknown environment.

PubMed

Li, Shoutao; Li, Lina; Lee, Gordon; Zhang, Hao

2014-01-01

This paper proposes a novel method to improve the efficiency of a swarm of robots searching in an unknown environment. The approach focuses on the process of feeding and individual coordination characteristics inspired by the foraging behavior in nature. A predatory strategy was used for searching; hence, this hybrid approach integrated a random search technique with a dynamic particle swarm optimization (DPSO) search algorithm. If a search robot could not find any target information, it used a random search algorithm for a global search. If the robot found any target information in a region, the DPSO search algorithm was used for a local search. This particle swarm optimization search algorithm is dynamic as all the parameters in the algorithm are refreshed synchronously through a communication mechanism until the robots find the target position, after which, the robots fall back to a random searching mode. Thus, in this searching strategy, the robots alternated between two searching algorithms until the whole area was covered. During the searching process, the robots used a local communication mechanism to share map information and DPSO parameters to reduce the communication burden and overcome hardware limitations. If the search area is very large, search efficiency may be greatly reduced if only one robot searches an entire region given the limited resources available and time constraints. In this research we divided the entire search area into several subregions, selected a target utility function to determine which subregion should be initially searched and thereby reduced the residence time of the target to improve search efficiency.

Biomimetic transport and rational drug delivery.

PubMed

Ranney, D F

2000-01-15

Medicine and pharmaceutics are encountering critical needs and opportunities for transvascular drug delivery that improves site targeting and tissue permeation by mimicking natural tissue addressing and transport mechanisms. This is driven by the accelerated development of genomic agents requiring targeted controlled release. Although rationally designed for in vitro activity, such agents are not highly effective in vivo, due to opsonization and degradation by plasma constituents, and failure to transport across the local vascular endothelium and tissue matrix. A growing knowledge of the addresses of the body can be applied to engineer "Bio-Logically" staged delivery systems with sequential bioaddressins complementary to the discontinuous compartments encountered--termed discontinuum pharmaceutics. Effective tissue targeting is accomplished by leukocytes, bacteria, and viruses. We are increasingly able to mimic their bioaddressins by genomic means. Approaches described in this commentary include: (a) endothelial-directed adhesion mediated by oligosaccharides and carbohydrates (e.g. dermatan sulfate as a mimic of sulfated CD44) and peptidomimetics interacting with adhesins, selectins, integrins, hyaluronans, and locally induced growth factors (e.g. vascular endothelial growth factor, VEGF) and coagulation factors (e.g. factor VIII antigen); (b) improved tissue permeation conferred by hydrophilically "cloaked" carrier systems; (c) "uncloaking" by matrix dilution or selective triggering near the target cells; and (d) target binding-internalization by terminally exposed hydrophobic moieties, cationic polymers, and receptor-binding lectins, peptides, or carbohydrates. This commentary also describes intermediate technology solutions (e.g. "hybrid drugs"), and highlights the high-resolution, dynamic magnetic resonance imaging and radiopharmaceutical imaging technologies plus the groups and organizations capable of accelerating these important initiatives.

Improvement of Aspergillus nidulans penicillin production by targeting AcvA to peroxisomes.

PubMed

Herr, Andreas; Fischer, Reinhard

2014-09-01

Aspergillus nidulans is able to synthesize penicillin and serves as a model to study the regulation of its biosynthesis. Only three enzymes are required to form the beta lactam ring tripeptide, which is comprised of l-cysteine, l-valine and l-aminoadipic acid. Whereas two enzymes, AcvA and IpnA localize to the cytoplasm, AatA resides in peroxisomes. Here, we tested a novel strategy to improve penicillin production, namely the change of the residence of the enzymes involved in the biosynthesis. We tested if targeting of AcvA or IpnA (or both) to peroxisomes would increase the penicillin yield. Indeed, AcvA peroxisomal targeting led to a 3.2-fold increase. In contrast, targeting IpnA to peroxisomes caused a complete loss of penicillin production. Overexpression of acvA, ipnA or aatA resulted in 1.4, 2.8 and 3.1-fold more penicillin, respectively in comparison to wildtype. Simultaneous overexpression of all three enzymes resulted even in 6-fold more penicillin. Combination of acvA peroxisomal targeting and overexpression of the gene led to 5-fold increase of the penicillin titer. At last, the number of peroxisomes was increased through overexpression of pexK. A strain with the double number of peroxisomes produced 2.3 times more penicillin. These results show that penicillin production can be triggered at several levels of regulation, one of which is the subcellular localization of the enzymes. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Human ergology that promotes participatory approach to improving safety, health and working conditions at grassroots workplaces: achievements and actions.

PubMed

Kawakami, Tsuyoshi

2011-12-01

Participatory approaches are increasingly applied to improve safety, health and working conditions of grassroots workplaces in Asia. The core concepts and methods in human ergology research such as promoting real work life studies, relying on positive efforts of local people (daily life-technology), promoting active participation of local people to identify practical solutions, and learning from local human networks to reach grassroots workplaces, have provided useful viewpoints to devise such participatory training programmes. This study was aimed to study and analyze how human ergology approaches were applied in the actual development and application of three typical participatory training programmes: WISH (Work Improvement for Safe Home) with home workers in Cambodia, WISCON (Work Improvement in Small Construction Sites) with construction workers in Thailand, and WARM (Work Adjustment for Recycling and Managing Waste) with waste collectors in Fiji. The results revealed that all the three programmes, in the course of their developments, commonly applied direct observation methods of the work of target workers before devising the training programmes, learned from existing local good examples and efforts, and emphasized local human networks for cooperation. These methods and approaches were repeatedly applied in grassroots workplaces by taking advantage of their the sustainability and impacts. It was concluded that human ergology approaches largely contributed to the developments and expansion of participatory training programmes and could continue to support the self-help initiatives of local people for promoting human-centred work.

A Computerized Microelectrode Recording to Magnetic Resonance Imaging Mapping System for Subthalamic Nucleus Deep Brain Stimulation Surgery.

PubMed

Dodani, Sunjay S; Lu, Charles W; Aldridge, J Wayne; Chou, Kelvin L; Patil, Parag G

2018-06-01

Accurate electrode placement is critical to the success of deep brain stimulation (DBS) surgery. Suboptimal targeting may arise from poor initial target localization, frame-based targeting error, or intraoperative brain shift. These uncertainties can make DBS surgery challenging. To develop a computerized system to guide subthalamic nucleus (STN) DBS electrode localization and to estimate the trajectory of intraoperative microelectrode recording (MER) on magnetic resonance (MR) images algorithmically during DBS surgery. Our method is based upon the relationship between the high-frequency band (HFB; 500-2000 Hz) signal from MER and voxel intensity on MR images. The HFB profile along an MER trajectory recorded during surgery is compared to voxel intensity profiles along many potential trajectories in the region of the surgically planned trajectory. From these comparisons of HFB recordings and potential trajectories, an estimate of the MER trajectory is calculated. This calculated trajectory is then compared to actual trajectory, as estimated by postoperative high-resolution computed tomography. We compared 20 planned, calculated, and actual trajectories in 13 patients who underwent STN DBS surgery. Targeting errors for our calculated trajectories (2.33 mm ± 0.2 mm) were significantly less than errors for surgically planned trajectories (2.83 mm ± 0.2 mm; P = .01), improving targeting prediction in 70% of individual cases (14/20). Moreover, in 4 of 4 initial MER trajectories that missed the STN, our method correctly indicated the required direction of targeting adjustment for the DBS lead to intersect the STN. A computer-based algorithm simultaneously utilizing MER and MR information potentially eases electrode localization during STN DBS surgery.

Community-made mobile videos as a mechanism for maternal, newborn and child health education in rural Uganda; a qualitative evaluation.

PubMed

Mutanda, Juliet Ntuulo; Waiswa, Peter; Namutamba, Sarah

2016-12-01

In Uganda, the maternal, newborn and child mortality is highest in rural areas, which are least served by health services and are also least reached by effective behavior change communication for health. Though maternal and child health related messages are available, they are still not culture and context specific for effective behaviour change. This study aimed at evaluating the feasibility of using locally made videos by local community groups in local languages as a channel for increasing knowledge, practices, demand and use of maternal and child health messages among women living in rural communities in Eastern Uganda. This paper describes the qualitative findings from a quasi experimental study targeting the rural semi-illiterate populations in hard to reach areas. Videos were developed and implemented based on Ministry of Health. Focus group discussions and KIs targeted pregnant and post natal mothers. Data transcription and content analysis was done. Local mobile community videos were effective in communicating knowledge about key maternal and child health messages to both women and their male partners. Locally made mobile community videos are effective in improving knowledge, attitudes, practices and use of maternal and child health messages among rural semi-illiterate communities.

Evidence That P-glycoprotein Inhibitor (Elacridar)-Loaded Nanocarriers Improve Epidermal Targeting of an Anticancer Drug via Absorptive Cutaneous Transporters Inhibition.

PubMed

Giacone, Daniela V; Carvalho, Vanessa F M; Costa, Soraia K P; Lopes, Luciana B

2018-02-01

Because P-glycoprotein (P-gp) plays an absorptive role in the skin, its pharmacological inhibition represents a strategy to promote cutaneous localization of anticancer agents that serve as its substrates, improving local efficacy while reducing systemic exposure. Here, we evaluated the ability of a nanoemulsion (NE) coencapsulating a P-gp inhibitor (elacridar) with the antitumor drug paclitaxel to promote epidermal targeting. Loaded NE displayed a nanometric size (45.2 ± 4.0 nm) and negative zeta potential (-4.2 ± 0.8 mV). Elacridar improved NE ability to inhibit verapamil-induced ATPase activity of P-gp; unloaded NE-inhibited P-gp when used at a concentration of 1500 μM, while elacridar encapsulation decreased this concentration by 3-fold (p <0.05). Elacridar-loaded NE reduced paclitaxel penetration into the dermis of freshly excised mice skin and its percutaneous permeation by 1.5- and 1.7-fold (p <0.05), respectively at 6 h, whereas larger drug amounts (1.4-fold, p <0.05) were obtained in viable epidermis. Assessment of cutaneous distribution of a fluorescent paclitaxel derivative confirmed the smaller delivery into the dermis at elacridar presence. In conclusion, we have provided novel evidence that NE containing elacridar exhibited a clear potential for P-gp inhibition and enabled epidermal targeting of paclitaxel, which in turn, can potentially reduce adverse effects associated with systemic exposure to anticancer therapy. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Surface Gravity Data Contribution to the Puerto Rico and U.S. Virgin Islands Geoid Model

NASA Astrophysics Data System (ADS)

Li, X.; Gerhards, C.; Holmes, S. A.; Saleh, J.; Shaw, B.

2015-12-01

The Gravity for the Redefinition of the American Vertical Datum (GRAV-D) project provides updated local gravity field information for the XGEOID15 models. In particular, its airborne gravity data in the area of Puerto Rico and U.S. Virgin Islands (PRVI) made substantial improvements (~60%) on the precision of the geoid models at the local GNSS/Leveling bench marks in the target area. Fortunately, PRVI is free of the huge systematic error in the North American Vertical Datum of 1988 (NAVD88). Thus, the airborne contribution was evaluated more realistically. In addition, the airborne data picked up more detailed gravity field information in the medium wavelength band (spherical harmonic degree 200 to 600) that are largely beyond the resolution of the current satellite missions, especially along the nearby ocean trench areas. Under this circumstance (significant airborne contributions in the medium band), local surface gravity data need to be examined more carefully than before during merging with the satellite and airborne information for local geoid improvement, especially considering the well-known systematic problems in the NGS historical gravity holdings (Saleh et al 2013 JoG). Initial tests showed that it is very important to maintain high consistency between the surface data sets and the airborne enhanced reference model. In addition, a new aggregation method (Gerhards 2014, Inverse Problems) will also be tested to optimally combine the local surface data with the reference model. The data cleaning and combining procedures in the target area will be summarized here as reference for future applications.

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

PubMed

Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

2014-04-01

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns

PubMed Central

Castleberry, Steven A.; Golberg, Alexander; Sharkh, Malak Abu; Khan, Saiqa; Almquist, Benjamin D.; Austen, William G.; Yarmush, Martin L.; Hammond, Paula T.

2017-01-01

Wound healing is an incredibly complex biological process that often results in thickened collagen-enriched healed tissue called scar. Cutaneous scars lack many functional structures of the skin such as hair follicles, sweat glands, and papillae. The absence of these structures contributes to a number of the long-term morbidities of wound healing, including loss of function for tissues, increased risk of re-injury, and aesthetic complications. Scar formation is a pervasive factor in our daily lives; however, in the case of serious traumatic injury, scars can create long-lasting complications due to contraction and poor tissue remodeling. Within this report we target the expression of connective tissue growth factor (CTGF), a key mediator of TGFβ pro-fibrotic response in cutaneous wound healing, with controlled local delivery of RNA interference. Through this work we describe both a thorough in vitro analysis of nanolayer coated sutures for the controlled delivery of siRNA and its application to improve scar outcomes in a third-degree burn induced scar model in rats. We demonstrate that the knockdown of CTGF significantly altered the local expression of αSMA, TIMP1, and Col1a1, which are known to play roles in scar formation. The knockdown of CTGF within the healing burn wounds resulted in improved tissue remodeling, reduced scar contraction, and the regeneration of papillary structures within the healing tissue. This work adds support to a number of previous reports that indicate CTGF as a potential therapeutic target for fibrosis. Additionally, we believe that the controlled local delivery of siRNA from ultrathin polymer coatings described within this work is a promising approach in RNA interference that could be applied in developing improved cancer therapies, regenerative medicine, and fundamental scientific research. PMID:27108403

Joint detection and tracking of size-varying infrared targets based on block-wise sparse decomposition

NASA Astrophysics Data System (ADS)

Li, Miao; Lin, Zaiping; Long, Yunli; An, Wei; Zhou, Yiyu

2016-05-01

The high variability of target size makes small target detection in Infrared Search and Track (IRST) a challenging task. A joint detection and tracking method based on block-wise sparse decomposition is proposed to address this problem. For detection, the infrared image is divided into overlapped blocks, and each block is weighted on the local image complexity and target existence probabilities. Target-background decomposition is solved by block-wise inexact augmented Lagrange multipliers. For tracking, label multi-Bernoulli (LMB) tracker tracks multiple targets taking the result of single-frame detection as input, and provides corresponding target existence probabilities for detection. Unlike fixed-size methods, the proposed method can accommodate size-varying targets, due to no special assumption for the size and shape of small targets. Because of exact decomposition, classical target measurements are extended and additional direction information is provided to improve tracking performance. The experimental results show that the proposed method can effectively suppress background clutters, detect and track size-varying targets in infrared images.

Action Enhances Acoustic Cues for 3-D Target Localization by Echolocating Bats

PubMed Central

Wohlgemuth, Melville J.

2016-01-01

Under natural conditions, animals encounter a barrage of sensory information from which they must select and interpret biologically relevant signals. Active sensing can facilitate this process by engaging motor systems in the sampling of sensory information. The echolocating bat serves as an excellent model to investigate the coupling between action and sensing because it adaptively controls both the acoustic signals used to probe the environment and movements to receive echoes at the auditory periphery. We report here that the echolocating bat controls the features of its sonar vocalizations in tandem with the positioning of the outer ears to maximize acoustic cues for target detection and localization. The bat’s adaptive control of sonar vocalizations and ear positioning occurs on a millisecond timescale to capture spatial information from arriving echoes, as well as on a longer timescale to track target movement. Our results demonstrate that purposeful control over sonar sound production and reception can serve to improve acoustic cues for localization tasks. This finding also highlights the general importance of movement to sensory processing across animal species. Finally, our discoveries point to important parallels between spatial perception by echolocation and vision. PMID:27608186

Specific muscle stabilizing as home exercises for persistent pelvic girdle pain after pregnancy: a randomized, controlled clinical trial.

PubMed

Gutke, Annelie; Sjödahl, Jenny; Oberg, Birgitta

2010-11-01

To investigate the efficacy of home-based specific stabilizing exercises focusing on the local stabilizing muscles as the only intervention in the treatment of persistent postpartum pelvic girdle pain. A prospective, randomized, single-blinded, clinically controlled study. Eighty-eight women with pelvic girdle pain were recruited 3 months after delivery. The treatment consisted of specific stabilizing exercises targeting the local trunk muscles. The reference group had a single telephone contact with a physiotherapist. Primary outcome was disability measured with Oswestry Disability Index. Secondary outcomes were pain, health-related quality of life (EQ-5D), symptom satisfaction, and muscle function. No significant differences between groups could be found at 3- or 6-month follow-up regarding primary outcome in disability. Within-group comparisons showed some improvement in both groups in terms of disability, pain, symptom satisfaction and muscle function compared with baseline, although the majority still experienced pelvic girdle pain. Treatment with this home-training concept of specific stabilizing exercises targeting the local muscles was no more effective in improving consequences of persistent postpartum pelvic girdle pain than the clinically natural course. Regardless of whether treatment with specific stabilizing exercises was carried out, the majority of women still experienced some back pain almost one year after pregnancy.

The use of shock waves in peripheral nerve regeneration: new perspectives?

PubMed

Hausner, Thomas; Nógrádi, Antal

2013-01-01

Low-energy extracorporeal shock wave treatment (ESWT) is a relatively new therapeutic tool that is widely used for the treatment of epicondylitis and plantar fasciitis and to foster bone and wound healing. Shock waves, sonic pulses with high energy impact, are thought to induce biochemical changes within the targeted tissues through mechanotransduction. The biological effects of ESWT are manifested in improved vascularization, the local release of growth factors, and local anti-inflammatory effects, but the target cells too are influenced. ESWT appears to have differential effects on peripheral nerves and has been proved to promote axonal regeneration after axotomy. This review discusses the effects of ESWT on intact and injured peripheral nerves and suggests a multiple mechanism of action. © 2013 Elsevier Inc. All rights reserved.

Frontline Field Epidemiology Training Programs as a Strategy to Improve Disease Surveillance and Response

PubMed Central

Lopez, Augusto; Perkins, Samantha; Lambert, Stephanie; Chace, Lesley; Noudeke, Nestor; Fall, Aissatou; Pedalino, Biagio

2017-01-01

Since 1980, Field Epidemiology Training Programs (FETPs) have trained highly qualified field epidemiologists to work for ministries of health (MOH) around the world. However, the 2013–2015 Ebola epidemic in West Africa, which primarily affected Guinea, Liberia, and Sierra Leone, demonstrated a lack of field epidemiologists at the local levels. Trained epidemiologists at these levels could have detected the Ebola outbreak earlier. In 2015, the US Centers for Disease Control and Prevention (CDC) launched FETP-Frontline, a 3-month field training program targeting local MOH staff in 24 countries to augment local public health capacity. As of December 2016, FETP-Frontline has trained 1,354 graduates in 24 countries. FETP-Frontline enhances global health security by training local public health staff to improve surveillance quality in their jurisdictions, which can be a valuable strategy to strengthen the capacity of countries to more rapidly detect, respond to, and contain public health emergencies at the source. PMID:29155657

Kalman filter data assimilation: targeting observations and parameter estimation.

PubMed

Bellsky, Thomas; Kostelich, Eric J; Mahalov, Alex

2014-06-01

This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly located observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.

Kalman filter data assimilation: Targeting observations and parameter estimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bellsky, Thomas, E-mail: bellskyt@asu.edu; Kostelich, Eric J.; Mahalov, Alex

2014-06-15

This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly locatedmore » observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.« less

Drug-induced amplification of nanoparticle targeting to tumors

PubMed Central

Lin, Kevin Y.; Kwon, Ester J.; Lo, Justin H.; Bhatia, Sangeeta N.

2018-01-01

Summary Nanomedicines have the potential to significantly impact cancer therapy by improving drug efficacy and decreasing off-target effects, yet our ability to efficiently home nanoparticles to disease sites remains limited. One frequently overlooked constraint of current active targeting schemes is the relative dearth of targetable antigens within tumors, which restricts the amount of cargo that can be delivered in a tumor-specific manner. To address this limitation, we exploit tumor-specific responses to drugs to construct a cooperative targeting system where a small molecule therapeutic modulates the disease microenvironment to amplify nanoparticle recruitment in vivo. We first administer a vascular disrupting agent, ombrabulin, which selectively affects tumors and leads to locally elevated presentation of the stress-related protein, p32. This increase in p32 levels provides more binding sites for circulating p32-targeted nanoparticles, enhancing their delivery of diagnostic or therapeutic cargos to tumors. We show that this cooperative targeting system recruits over five times higher doses of nanoparticles to tumors and decreases tumor burden when compared with non-cooperative controls. These results suggest that using nanomedicine in conjunction with drugs that enhance the presentation of target antigens in the tumor environment may be an effective strategy for improving the diagnosis and treatment of cancer. PMID:29731806

The reliability and internal consistency of one-shot and flicker change detection for measuring individual differences in visual working memory capacity.

PubMed

Pailian, Hrag; Halberda, Justin

2015-04-01

We investigated the psychometric properties of the one-shot change detection task for estimating visual working memory (VWM) storage capacity-and also introduced and tested an alternative flicker change detection task for estimating these limits. In three experiments, we found that the one-shot whole-display task returns estimates of VWM storage capacity (K) that are unreliable across set sizes-suggesting that the whole-display task is measuring different things at different set sizes. In two additional experiments, we found that the one-shot single-probe variant shows improvements in the reliability and consistency of K estimates. In another additional experiment, we found that a one-shot whole-display-with-click task (requiring target localization) also showed improvements in reliability and consistency. The latter results suggest that the one-shot task can return reliable and consistent estimates of VWM storage capacity (K), and they highlight the possibility that the requirement to localize the changed target is what engenders this enhancement. Through a final series of four experiments, we introduced and tested an alternative flicker change detection method that also requires the observer to localize the changing target and that generates, from response times, an estimate of VWM storage capacity (K). We found that estimates of K from the flicker task correlated with estimates from the traditional one-shot task and also had high reliability and consistency. We highlight the flicker method's ability to estimate executive functions as well as VWM storage capacity, and discuss the potential for measuring multiple abilities with the one-shot and flicker tasks.

Surrogate MRI markers for hyperthermia-induced release of doxorubicin from thermosensitive liposomes in tumors.

PubMed

Peller, Michael; Willerding, Linus; Limmer, Simone; Hossann, Martin; Dietrich, Olaf; Ingrisch, Michael; Sroka, Ronald; Lindner, Lars H

2016-09-10

The efficacy of systemically applied, classical anti-cancer drugs is limited by insufficient selectivity to the tumor and the applicable dose is limited by side effects. Efficacy could be further improved by targeting of the drug to the tumor. Using thermosensitive liposomes (TSL) as a drug carrier, targeting is achieved by control of temperature in the target volume. In such an approach, effective local hyperthermia (40-43°C) (HT) of the tumor is considered essential but technically challenging. Thus, visualization of local heating and drug release using TSL is considered an important tool for further improvement. Visualization and feasibility of chemodosimetry by magnetic resonance imaging (MRI) has previously been demonstrated using TSL encapsulating both, contrast agent (CA) and doxorubicin (DOX) simultaneously in the same TSL. Dosimetry has been facilitated using T1-relaxation time change as a surrogate marker for DOX deposition in the tumor. To allow higher loading of the TSL and to simplify clinical development of new TSL formulations a new approach using a mixture of TSL either loaded with DOX or MRI-CA is suggested. This was successfully tested using phosphatidyldiglycerol-based TSL (DPPG2-TSL) in Brown Norway rats with syngeneic soft tissue sarcomas (BN175) implanted at both hind legs. After intravenous application of DOX-TSL and CA-TSL, heating of one tumor above 40°C for 1h using laser light resulted in highly selective DOX uptake. The DOX-concentration in the heated tumor tissue compared to the non-heated tumor showed an almost 10-fold increase. T1 and additional MRI surrogate parameters such as signal phase change were correlated to intratumoral DOX concentration. Visualization of DOX delivery in the sense of a chemodosimetry was demonstrated. Although phase-based MR-thermometry was affected by CA-TSL, phase information was found suitable for DOX concentration assessment. Local differences of DOX concentration in the tumors indicated the need for visualization of drug release for further improvement of targeting. Copyright © 2016 Elsevier B.V. All rights reserved.

Magnetic nanoparticle-based approaches to locally target therapy and enhance tissue regeneration in vivo

PubMed Central

Sensenig, Richard; Sapir, Yulia; MacDonald, Cristin; Cohen, Smadar; Polyak, Boris

2013-01-01

Magnetic-based systems utilizing superparamagnetic nanoparticles and a magnetic field gradient to exert a force on these particles have been used in a wide range of biomedical applications. This review is focused on drug targeting applications that require penetration of a cellular barrier as well as strategies to improve the efficacy of targeting in these biomedical applications. Another focus of this review is regenerative applications utilizing tissue engineered scaffolds prepared with the aid of magnetic particles, the use of remote actuation for release of bioactive molecules and magneto–mechanical cell stimulation, cell seeding and cell patterning. PMID:22994959

Design of a targeted peptide nucleic acid prodrug to inhibit hepatic human microsomal triglyceride transfer protein expression in hepatocytes.

PubMed

Biessen, Erik A L; Sliedregt-Bol, Karen; 'T Hoen, Peter A Chr; Prince, Perry; Van der Bilt, Erica; Valentijn, A Rob P M; Meeuwenoord, Nico J; Princen, Hans; Bijsterbosch, Martin K; Van der Marel, Gijs A; Van Boom, Jacques H; Van Berkel, Theo J C

2002-01-01

In this study, we present the design and synthesis of an antisense peptide nucleic acid (asPNA) prodrug, which displays an improved biodistribution profile and an equally improved capacity to reduce the levels of target mRNA. The prodrug, K(GalNAc)(2)-asPNA, comprised of a 14-mer sequence complementary to the human microsomal triglyceride transfer protein (huMTP) gene, conjugated to a high-affinity tag for the hepatic asialoglycoprotein receptor (K(GalNAc)(2)). The prodrug was avidly bound and rapidly internalized by HepG2s. After iv injection into mice, K(GalNAc)(2)-asPNA accumulated in the parenchymal liver cells to a much greater extent than nonconjugated PNA (46% +/- 1% vs 3.1% +/- 0.5% of the injected dose, respectively). The prodrug was able to reduce MTP mRNA levels in HepG2 cells by 35-40% (P < 0.02) at 100 nM in an asialoglycoprotein receptor- and sequence-dependent fashion. In conclusion, hepatocyte-targeted PNA prodrugs combine a greatly improved tropism with an enhanced local intracellular availability and activity, making them attractive therapeutics to lower the expression level of hepatic target genes such as MTP.

The Identification of Filters and Interdependencies for Effective Resource Allocation: Coupling the Mitigation of Natural Hazards to Economic Development.

NASA Astrophysics Data System (ADS)

Agar, S. M.; Kunreuther, H.

2005-12-01

Policy formulation for the mitigation and management of risks posed by natural hazards requires that governments confront difficult decisions for resource allocation and be able to justify their spending. Governments also need to recognize when spending offers little improvement and the circumstances in which relatively small amounts of spending can make substantial differences. Because natural hazards can have detrimental impacts on local and regional economies, patterns of economic development can also be affected by spending decisions for disaster mitigation. This paper argues that by mapping interdependencies among physical, social and economic factors, governments can improve resource allocation to mitigate the risks of natural hazards while improving economic development on local and regional scales. Case studies of natural hazards in Turkey have been used to explore specific "filters" that act to modify short- and long-term outcomes. Pre-event filters can prevent an event from becoming a natural disaster or change a routine event into a disaster. Post-event filters affect both short and long-term recovery and development. Some filters cannot be easily modified by spending (e.g., rural-urban migration) but others (e.g., land-use practices) provide realistic spending targets. Net social benefits derived from spending, however, will also depend on the ways by which filters are linked, or so-called "interdependencies". A single weak link in an interdependent system, such as a power grid, can trigger a cascade of failures. Similarly, weak links in social and commercial networks can send waves of disruption through communities. Conversely, by understanding the positive impacts of interdependencies, spending can be targeted to maximize net social benefits while mitigating risks and improving economic development. Detailed information on public spending was not available for this study but case studies illustrate how networks of interdependent filters can modify social benefits and costs. For example, spending after the 1992 Erzincan earthquake targeted local businesses but limited alternative employment, labor losses and diminished local markets all contributed to economic stagnation. Spending after the 1995 Dinar earthquake provided rent subsidies, supporting a major exodus from the town. Consequently many local people were excluded from reconstruction decisions and benefits offered by reconstruction funds. After the 1999 Marmara earthquakes, a 3-year economic decline in Yalova illustrates the vulnerability of local economic stability to weak regulation enforcement by a few agents. A resource allocation framework indicates that government-community relations, lack of economic diversification, beliefs, and compensation are weak links for effective spending. Stronger positive benefits could be achieved through spending to target land-use regulation enforcement, labor losses, time-critical needs of small businesses, and infrastructure. While the impacts of the Marmara earthquakes were devastating, strong commercial networks and international interests helped to re-establish the regional economy. Interdependencies may have helped to drive a recovery. Smaller events in eastern Turkey, however, can wipe out entire communities and can have long-lasting impacts on economic development. These differences may accelerate rural to urban migration and perpetuate regional economic divergence in the country. 1: Research performed in the Wharton MBA Program, Univ. of Pennsylvania.

Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis.

PubMed

Wang, Junjuan; Wang, Jiaqiu; Lu, Ping; Cai, Youzhi; Wang, Yafei; Hong, Lan; Ren, Hao; Heng, Boon Chin; Liu, Hua; Zhou, Jing; Ouyang, Hongwei

2015-09-01

FTY720 has recently been approved as an oral drug for treating relapsing forms of multiple sclerosis, and exerts its therapeutic effect by acting as an immunological inhibitor targeting the sphingosine-1-phosphate (S1P) receptor subtype (S1P1) of T cells. Recently studies demonstrated positive efficacy of this drug on spinal cord injury (SCI) in animal models after systemic administration, albeit with significant adverse side effects. We hereby hypothesize that localized delivery of FTY720 can promote SCI recovery by reducing pathological astrogliosis. The mechanistic functions of FTY720 were investigated in vitro and in vivo utilizing immunofluorescence, histology, MRI and behavioral analysis. The in vitro study showed that FTY720 can reduce astrocyte migration and proliferation activated by S1P. FTY720 can prolong internalization of S1P1 and exert antagonistic effects on S1P1. In vivo study of SCI animal models demonstrated that local delivery of FTY720 with polycaprolactone (PCL) membrane significantly decreased S1P1 expression and glial scarring compared with the control group. Furthermore, FTY720-treated groups exhibited less cavitation volume and neuron loss, which significantly improved recovery of motor function. These findings demonstrated that localized delivery of FTY720 can promote SCI recovery by targeting the S1P1 receptor of astrocytes, provide a new therapeutic strategy for SCI treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Visuospatial selective attention in chickens.

PubMed

Sridharan, Devarajan; Ramamurthy, Deepa L; Schwarz, Jason S; Knudsen, Eric I

2014-05-13

Voluntary control of attention promotes intelligent, adaptive behaviors by enabling the selective processing of information that is most relevant for making decisions. Despite extensive research on attention in primates, the capacity for selective attention in nonprimate species has never been quantified. Here we demonstrate selective attention in chickens by applying protocols that have been used to characterize visual spatial attention in primates. Chickens were trained to localize and report the vertical position of a target in the presence of task-relevant distracters. A spatial cue, the location of which varied across individual trials, indicated the horizontal, but not vertical, position of the upcoming target. Spatial cueing improved localization performance: accuracy (d') increased and reaction times decreased in a space-specific manner. Distracters severely impaired perceptual performance, and this impairment was greatly reduced by spatial cueing. Signal detection analysis with an "indecision" model demonstrated that spatial cueing significantly increased choice certainty in localizing targets. By contrast, error-aversion certainty (certainty of not making an error) remained essentially constant across cueing protocols, target contrasts, and individuals. The results show that chickens shift spatial attention rapidly and dynamically, following principles of stimulus selection that closely parallel those documented in primates. The findings suggest that the mechanisms that control attention have been conserved through evolution, and establish chickens--a highly visual species that is easily trained and amenable to cutting-edge experimental technologies--as an attractive model for linking behavior to neural mechanisms of selective attention.

Optimization of prostate biopsy: the role of magnetic resonance imaging targeted biopsy in detection, localization and risk assessment.

PubMed

Bjurlin, Marc A; Meng, Xiaosong; Le Nobin, Julien; Wysock, James S; Lepor, Herbert; Rosenkrantz, Andrew B; Taneja, Samir S

2014-09-01

Optimization of prostate biopsy requires addressing the shortcomings of standard systematic transrectal ultrasound guided biopsy, including false-negative rates, incorrect risk stratification, detection of clinically insignificant disease and the need for repeat biopsy. Magnetic resonance imaging is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of biopsy, and thereby enhances clinical risk assessment and improves the ability to appropriately counsel patients regarding therapy. In this review we 1) summarize the various sequences that comprise a prostate multiparametric magnetic resonance imaging examination along with its performance characteristics in cancer detection, localization and reporting standards; 2) evaluate potential applications of magnetic resonance imaging targeting in prostate biopsy among men with no previous biopsy, a negative previous biopsy and those with low stage cancer; and 3) describe the techniques of magnetic resonance imaging targeted biopsy and comparative study outcomes. A bibliographic search covering the period up to October 2013 was conducted using MEDLINE®/PubMed®. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Multiparametric magnetic resonance imaging consists of anatomical T2-weighted imaging coupled with at least 2 functional imaging techniques. It has demonstrated improved prostate cancer detection sensitivity up to 80% in the peripheral zone and 81% in the transition zone. A prostate cancer magnetic resonance imaging suspicion score has been developed, and is depicted using the Likert or PI-RADS (Prostate Imaging Reporting and Data System) scale for better standardization of magnetic resonance imaging interpretation and reporting. Among men with no previous biopsy, magnetic resonance imaging increases the frequency of significant cancer detection to 50% in low risk and 71% in high risk patients. In low risk men the negative predictive value of a combination of negative magnetic resonance imaging with prostate volume parameters is nearly 98%, suggesting a potential role in avoiding biopsy and reducing over detection/overtreatment. Among men with a previous negative biopsy 72% to 87% of cancers detected by magnetic resonance imaging guidance are clinically significant. Among men with a known low risk cancer, repeat biopsy using magnetic resonance targeting demonstrates a high likelihood of confirming low risk disease in low suspicion score lesions and of upgrading in high suspicion score lesions. Techniques of magnetic resonance imaging targeted biopsy include visual estimation transrectal ultrasound guided biopsy; software co-registered magnetic resonance imaging-ultrasound, transrectal ultrasound guided biopsy; and in-bore magnetic resonance imaging guided biopsy. Although the improvement in accuracy and efficiency of visual estimation biopsy compared to systematic appears limited, co-registered magnetic resonance imaging-ultrasound biopsy as well as in-bore magnetic resonance imaging guided biopsy appear to increase cancer detection rates in conjunction with increasing suspicion score. Use of magnetic resonance imaging for targeting prostate biopsies has the potential to reduce the sampling error associated with conventional biopsy by providing better disease localization and sampling. More accurate risk stratification through improved cancer sampling may impact therapeutic decision making. Optimal clinical application of magnetic resonance imaging targeted biopsy remains under investigation. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Frequency-Modulated, Continuous-Wave Laser Ranging Using Photon-Counting Detectors

NASA Technical Reports Server (NTRS)

Erkmen, Baris I.; Barber, Zeb W.; Dahl, Jason

2014-01-01

Optical ranging is a problem of estimating the round-trip flight time of a phase- or amplitude-modulated optical beam that reflects off of a target. Frequency- modulated, continuous-wave (FMCW) ranging systems obtain this estimate by performing an interferometric measurement between a local frequency- modulated laser beam and a delayed copy returning from the target. The range estimate is formed by mixing the target-return field with the local reference field on a beamsplitter and detecting the resultant beat modulation. In conventional FMCW ranging, the source modulation is linear in instantaneous frequency, the reference-arm field has many more photons than the target-return field, and the time-of-flight estimate is generated by balanced difference- detection of the beamsplitter output, followed by a frequency-domain peak search. This work focused on determining the maximum-likelihood (ML) estimation algorithm when continuous-time photoncounting detectors are used. It is founded on a rigorous statistical characterization of the (random) photoelectron emission times as a function of the incident optical field, including the deleterious effects caused by dark current and dead time. These statistics enable derivation of the Cramér-Rao lower bound (CRB) on the accuracy of FMCW ranging, and derivation of the ML estimator, whose performance approaches this bound at high photon flux. The estimation algorithm was developed, and its optimality properties were shown in simulation. Experimental data show that it performs better than the conventional estimation algorithms used. The demonstrated improvement is a factor of 1.414 over frequency-domainbased estimation. If the target interrogating photons and the local reference field photons are costed equally, the optimal allocation of photons between these two arms is to have them equally distributed. This is different than the state of the art, in which the local field is stronger than the target return. The optimal processing of the photocurrent processes at the outputs of the two detectors is to perform log-matched filtering followed by a summation and peak detection. This implies that neither difference detection, nor Fourier-domain peak detection, which are the staples of the state-of-the-art systems, is optimal when a weak local oscillator is employed.

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

An improved artifact removal in exposure fusion with local linear constraints

NASA Astrophysics Data System (ADS)

Zhang, Hai; Yu, Mali

2018-04-01

In exposure fusion, it is challenging to remove artifacts because of camera motion and moving objects in the scene. An improved artifact removal method is proposed in this paper, which performs local linear adjustment in artifact removal progress. After determining a reference image, we first perform high-dynamic-range (HDR) deghosting to generate an intermediate image stack from the input image stack. Then, a linear Intensity Mapping Function (IMF) in each window is extracted based on the intensities of intermediate image and reference image, the intensity mean and variance of reference image. Finally, with the extracted local linear constraints, we reconstruct a target image stack, which can be directly used for fusing a single HDR-like image. Some experiments have been implemented and experimental results demonstrate that the proposed method is robust and effective in removing artifacts especially in the saturated regions of the reference image.

75 FR 29740 - Office of Elementary and Secondary Education; Overview Information; Gulf Coast Recovery Grant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

... assist local educational agencies (LEAs) in improving education in areas affected by Hurricanes Katrina... eligible for individual assistance due to damage caused by Hurricanes Katrina, Ike, or Gustav. For the... impact of the hurricane(s) on each school targeted for services under the project (10 points). Note: In...

A Case Study: Innovation of Internal Teaching and Learning Evaluation System in Higher Education Institutions

ERIC Educational Resources Information Center

Huiru, Yin

2009-01-01

The ultimate target of the education and teaching reform in higher education institutions is to improve the quality of teaching and talent training. As a key comprehensive university under the jurisdiction of the provincial government, Heilongjiang University sees its responsibility as training qualified talent to promote local economic…

Improving Education for Migrant-Background Students: A Transatlantic Comparison of School Funding

ERIC Educational Resources Information Center

Sugarman, Julie; Morris-Lange, Simon; McHugh, Margie

2016-01-01

The educational needs of migrant-background students in primary and secondary schools pose a growing challenge for policymakers and educators around the world. Some national, regional, and local governments have well-designed systems of support for such students, while others are just beginning to establish targeted policies and practices to meet…

Antibiotic use and good practice in 314 French hospitals: The 2010 SPA2 prevalence study.

PubMed

Alfandari, S; Robert, J; Péan, Y; Rabaud, C; Bedos, J P; Varon, E; Lepape, A; Bru, J P; Gauzit, R

2015-01-01

We aimed to assess antibiotic prescriptions to identify potential targets for improvement. We conducted a point prevalence survey (November 2010) of antibiotic use in 314 voluntary hospitals recruited by the French Infectious Diseases Society (SPILF) and the National Observatory for Epidemiology of Bacterial Resistance to Antimicrobials (ONERBA). Data were entered online, immediately analyzed and exported. The prevalence of antibiotic use was 19.5% (9059/46,446patients). A higher prevalence was observed in the infectious disease (58.4%), hematology (58%), and intensive care (48.7%) units. The three most frequently used antibiotic classes were aminopenicillins (23.8%), fluoroquinolones (17.9%), and 3rd-generation cephalosporins (16.7%). A monotherapy was prescribed to 64% of patients. The reasons for the antibiotic prescription were written in the medical records of 74% of patients and 62% were consistent with the local guidelines. Our results are similar to that of other studies. Various local targets for improvement have been identified to help hospitals define a better antibiotic stewardship. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Progress in Rectal Cancer Treatment

PubMed Central

Ceelen, Wim P.

2012-01-01

The dramatic improvement in local control of rectal cancer observed during the last decades is to be attributed to attention to surgical technique and to the introduction of neoadjuvant therapy regimens. Nevertheless, systemic relapse remains frequent and is currently insufficiently addressed. Intensification of neoadjuvant therapy by incorporating chemotherapy with or without targeted agents before the start of (chemo)radiation or during the waiting period to surgery may present an opportunity to improve overall survival. An increasing number of patients can nowadays undergo sphincter preserving surgery. In selected patients, local excision or even a “wait and see” approach may be feasible following active neoadjuvant therapy. Molecular and genetic biomarkers as well as innovative imaging techniques may in the future allow better selection of patients for this treatment option. Controversy persists concerning the selection of patients for adjuvant chemotherapy and/or targeted therapy after neoadjuvant regimens. The currently available evidence suggests that in complete pathological responders long-term outcome is excellent and adjuvant therapy may be omitted. The results of ongoing trials will help to establish the ideal tailored approach in resectable rectal cancer. PMID:22970381

WE-AB-BRA-01: 3D-2D Image Registration for Target Localization in Spine Surgery: Comparison of Similarity Metrics Against Robustness to Content Mismatch

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Silva, T; Ketcha, M; Siewerdsen, J H

Purpose: In image-guided spine surgery, mapping 3D preoperative images to 2D intraoperative images via 3D-2D registration can provide valuable assistance in target localization. However, the presence of surgical instrumentation, hardware implants, and soft-tissue resection/displacement causes mismatches in image content, confounding existing registration methods. Manual/semi-automatic methods to mask such extraneous content is time consuming, user-dependent, error prone, and disruptive to clinical workflow. We developed and evaluated 2 novel similarity metrics within a robust registration framework to overcome such challenges in target localization. Methods: An IRB-approved retrospective study in 19 spine surgery patients included 19 preoperative 3D CT images and 50 intraoperativemore » mobile radiographs in cervical, thoracic, and lumbar spine regions. A neuroradiologist provided truth definition of vertebral positions in CT and radiography. 3D-2D registration was performed using the CMA-ES optimizer with 4 gradient-based image similarity metrics: (1) gradient information (GI); (2) gradient correlation (GC); (3) a novel variant referred to as gradient orientation (GO); and (4) a second variant referred to as truncated gradient correlation (TGC). Registration accuracy was evaluated in terms of the projection distance error (PDE) of the vertebral levels. Results: Conventional similarity metrics were susceptible to gross registration error and failure modes associated with the presence of surgical instrumentation: for GI, the median PDE and interquartile range was 33.0±43.6 mm; similarly for GC, PDE = 23.0±92.6 mm respectively. The robust metrics GO and TGC, on the other hand, demonstrated major improvement in PDE (7.6 ±9.4 mm and 8.1± 18.1 mm, respectively) and elimination of gross failure modes. Conclusion: The proposed GO and TGC similarity measures improve registration accuracy and robustness to gross failure in the presence of strong image content mismatch. Such registration capability could offer valuable assistance in target localization without disruption of clinical workflow. G. Kleinszig and S. Vogt are employees of Siemens Healthcare.« less

Primary small-bowel malignancy: update in tumor biology, markers, and management strategies.

PubMed

Shenoy, Santosh

2014-12-01

Primary small-bowel malignancies (SBM) are rare tumors but their incidence is rising. An estimated 9160 new cases and 1210 deaths due to SBM may occur in the USA in 2014. We review advances made in tumor biology, immunohistochemistry, and discuss treatment strategies for these malignancies. Relevant articles from PubMed/Medline and Embase searches were collected using the phrases "small-bowel adenocarcinoma, gastrointestinal carcinoids, gastrointestinal stromal tumors, small-bowel leiomyosarcoma, and small-bowel lymphoma". Advances in imaging techniques such as wireless capsule endoscopy, CT and MRI enterography, and endoscopy (balloon enteroscopy) along with discovery of molecular markers such as c-kit and PDGFRA for GIST tumors have improved our ability to diagnose, localize, and treat these patients. Early detection and surgical resection offers the best chance for long-term survival in all tumors except bowel lymphoma where chemotherapy plays the main role. Adjuvant therapy with imatinib has improved overall survival for GIST tumors, somatostatin analogs have improved symptoms and also inhibited tumor growth and stabilized metastatic disease in carcinoid disease, but chemotherapy has not improved survival for adenocarcinoma. Recent advances in molecular characterization holds promise in novel targeted therapies. Currently ongoing trials are exploring efficacy of targeted therapies and role of adjuvant therapy for adenocarcinoma and results are awaited. Early detection and aggressive surgical therapy for all localized tumors and lymph node sampling particularly for adenocarcinoma remains the main treatment modality.

Improving polio vaccination coverage in Nigeria through the use of geographic information system technology.

PubMed

Barau, Inuwa; Zubairu, Mahmud; Mwanza, Michael N; Seaman, Vincent Y

2014-11-01

Historically, microplanning for polio vaccination campaigns in Nigeria relied on inaccurate and incomplete hand-drawn maps, resulting in the exclusion of entire settlements and missed children. The goal of this work was to create accurate, coordinate-based maps for 8 polio-endemic states in northern Nigeria to improve microplanning and support tracking of vaccination teams, thereby enhancing coverage, supervision, and accountability. Settlement features were identified in the target states, using high-resolution satellite imagery. Field teams collected names and geocoordinates for each settlement feature, with the help of local guides. Global position system (GPS) tracking of vaccination teams was conducted in selected areas and daily feedback provided to supervisors. Geographic information system (GIS)-based maps were created for 2238 wards in the 8 target states. The resulting microplans included all settlements and more-efficient team assignments, owing to the improved spatial reference. GPS tracking was conducted in 111 high-risk local government areas, resulting in improved team performance and the identification of missed/poorly covered settlements. Accurate and complete maps are a necessary part of an effective polio microplan, and tracking vaccinators gives supervisors a tool to ensure that all settlements are visited. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Virtual local target method for avoiding local minimum in potential field based robot navigation.

PubMed

Zou, Xi-Yong; Zhu, Jing

2003-01-01

A novel robot navigation algorithm with global path generation capability is presented. Local minimum is a most intractable but is an encountered frequently problem in potential field based robot navigation. Through appointing appropriately some virtual local targets on the journey, it can be solved effectively. The key concept employed in this algorithm are the rules that govern when and how to appoint these virtual local targets. When the robot finds itself in danger of local minimum, a virtual local target is appointed to replace the global goal temporarily according to the rules. After the virtual target is reached, the robot continues on its journey by heading towards the global goal. The algorithm prevents the robot from running into local minima anymore. Simulation results showed that it is very effective in complex obstacle environments.

Using a Geographic Information System to Improve Childhood Lead-Screening Efforts

PubMed Central

2013-01-01

The Idaho Division of Public Health conducted a pilot study to produce a lead-exposure–risk map to help local and state agencies better target childhood lead-screening efforts. Priority lead-screening areas, at the block group level, were created by using county tax assessor data and geographic information system software. A series of maps were produced, indicating childhood lead-screening prevalence in areas in which there was high potential for exposure to lead. These maps could enable development of more systematically targeted and cost-effective childhood lead-screening efforts. PMID:23764346

A Collaborative Secure Localization Algorithm Based on Trust Model in Underwater Wireless Sensor Networks

PubMed Central

Han, Guangjie; Liu, Li; Jiang, Jinfang; Shu, Lei; Rodrigues, Joel J.P.C.

2016-01-01

Localization is one of the hottest research topics in Underwater Wireless Sensor Networks (UWSNs), since many important applications of UWSNs, e.g., event sensing, target tracking and monitoring, require location information of sensor nodes. Nowadays, a large number of localization algorithms have been proposed for UWSNs. How to improve location accuracy are well studied. However, few of them take location reliability or security into consideration. In this paper, we propose a Collaborative Secure Localization algorithm based on Trust model (CSLT) for UWSNs to ensure location security. Based on the trust model, the secure localization process can be divided into the following five sub-processes: trust evaluation of anchor nodes, initial localization of unknown nodes, trust evaluation of reference nodes, selection of reference node, and secondary localization of unknown node. Simulation results demonstrate that the proposed CSLT algorithm performs better than the compared related works in terms of location security, average localization accuracy and localization ratio. PMID:26891300

Technological advances in radiotherapy for cervical cancer.

PubMed

Walsh, Lorraine; Morgia, Marita; Fyles, Anthony; Milosevic, Michael

2011-09-01

To discuss the important technological advances that have taken place in the planning and delivery of both external beam radiotherapy and brachytherapy for patients with locally advanced cervical cancer, and the implications for improved clinical outcomes. Technological advances in external beam radiation treatment and brachytherapy for patients with cervical cancer allow more precise targeting of tumour and relative sparing of surrounding normal organs and tissues. Early evidence is emerging to indicate that these advances will translate into improvements in tumour control and reduced side effects. However, there are patient, tumour and treatment-related factors that can detract from these benefits. Foremost among these is complex, unpredictable and sometimes dramatic internal tumour and normal organ motion during treatment. The focus of current research and clinical development is on tracking internal anatomic change in individual patients and adapting treatment plans as required to assure that optimal tumour coverage and normal tissue sparing is maintained at all times. The success of this approach will depend on clear definitions of target volumes, high resolution daily soft tissue imaging, and new software tools for rapid contouring, treatment planning and quality assurance. Radiation treatment of locally advanced cervical cancer is evolving rapidly, driven by advances in technology, towards more individualized patient care that has the potential to substantially improve clinical outcomes.

Small target pre-detection with an attention mechanism

NASA Astrophysics Data System (ADS)

Wang, Yuehuan; Zhang, Tianxu; Wang, Guoyou

2002-04-01

We introduce the concept of predetection based on an attention mechanism to improve the efficiency of small-target detection by limiting the image region of detection. According to the characteristics of small-target detection, local contrast is taken as the only feature in predetection and a nonlinear sampling model is adopted to make the predetection adaptive to detect small targets with different area sizes. To simplify the predetection itself and decrease the false alarm probability, neighboring nodes in the sampling grid are used to generate a saliency map, and a short-term memory is adopted to accelerate the `pop-out' of targets. We discuss the fact that the proposed approach is simple enough in computational complexity. In addition, even in a cluttered background, attention can be led to targets in a satisfying few iterations, which ensures that the detection efficiency will not be decreased due to false alarms. Experimental results are presented to demonstrate the applicability of the approach.

Changes in intrinsic local connectivity after reading intervention in children with autism.

PubMed

Maximo, Jose O; Murdaugh, Donna L; O'Kelley, Sarah; Kana, Rajesh K

2017-12-01

Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery-based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs-fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD-EXP; n=14) and a Wait-list control group (ASD-WLC; n=14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4-h per day, 10-weeks, 200h of face-to-face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD-EXP group showed significant improvement, compared to the ASD-WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD-EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD-WLC group post-intervention; (III) intervention-related changes in local brain connectivity were observed in the ASD-EXP from pre to post-intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs. Published by Elsevier Inc.

SU-E-T-170: Characterization of the Location, Extent, and Proximity to Critical Structures of Target Volumes Provides Detail for Improved Outcome Predictions Among Pancreatic Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Z; Moore, J; Rosati, L

Purpose: In radiotherapy, size, location and proximity of the target to critical structures influence treatment decisions. It has been shown that proximity of the target predicts dosimetric sparing of critical structures. In addition to dosimetry, precise location of disease has further implications such as tumor invasion, or proximity to major arteries that inhibit surgery. Knowledge of which patients can be converted to surgical candidates by radiation may have high impact on future treat/no-treat decisions. We propose a method to improve our characterization of the location of pancreatic cancer and treatment volume extent with respect to nearby arteries with the goalmore » of developing features to improve clinical predictions and decisions. Methods: Oncospace is a local learning health system that systematically captures clinical outcomes and all aspects of radiotherapy treatment plans, including overlap volume histograms (OVH) – a measure of spatial relationships between two structures. Minimum and maximum distances of PTV and OARs based on OVH, PTV volume, anatomic location by ICD-9 code, and surgical outcome were queried. Normalized distance to center from the left and right kidney was calculated to indicate tumor location and laterality. Distance to critical arteries (celiac, superior mesenteric, common hepatic) is validated by surgical status (borderline resectable, locally advanced converted to resectable). Results: There were 205 pancreas stereotactic body radiotherapy patients treated from 2009–2015 queried. Location/laterality of tumor based on kidney OVH show strong trends between location by OVH and by ICD-9. Compared to the locally advanced group, the borderline resectable group showed larger geometrical distance from critical arteries (p=0.03). Conclusion: Our platform enabled analysis of shape/size-location relationships. These data suggest that PTV volume and attention to distance between PTVs and surrounding OARs and major arteries may be promising for improving characterization of treatment anatomy that can refine our ability for outcome predictions and decision making. Elekta, Toshiba.« less

Improved protein model quality assessments by changing the target function.

PubMed

Uziela, Karolis; Menéndez Hurtado, David; Shu, Nanjiang; Wallner, Björn; Elofsson, Arne

2018-06-01

Protein modeling quality is an important part of protein structure prediction. We have for more than a decade developed a set of methods for this problem. We have used various types of description of the protein and different machine learning methodologies. However, common to all these methods has been the target function used for training. The target function in ProQ describes the local quality of a residue in a protein model. In all versions of ProQ the target function has been the S-score. However, other quality estimation functions also exist, which can be divided into superposition- and contact-based methods. The superposition-based methods, such as S-score, are based on a rigid body superposition of a protein model and the native structure, while the contact-based methods compare the local environment of each residue. Here, we examine the effects of retraining our latest predictor, ProQ3D, using identical inputs but different target functions. We find that the contact-based methods are easier to predict and that predictors trained on these measures provide some advantages when it comes to identifying the best model. One possible reason for this is that contact based methods are better at estimating the quality of multi-domain targets. However, training on the S-score gives the best correlation with the GDT_TS score, which is commonly used in CASP to score the global model quality. To take the advantage of both of these features we provide an updated version of ProQ3D that predicts local and global model quality estimates based on different quality estimates. © 2018 Wiley Periodicals, Inc.

Decomposition of the Multistatic Response Matrix and Target Characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chambers, D H

2008-02-14

Decomposition of the time-reversal operator for an array, or equivalently the singular value decomposition of the multistatic response matrix, has been used to improve imaging and localization of targets in complicated media. Typically, each singular value is associated with one scatterer even though it has been shown in several cases that a single scatterer can generate several singular values. In this paper we review the analysis of the time-reversal operator (TRO), or equivalently the multistatic response matrix (MRM), of an array system and a small target. We begin with two-dimensional scattering from a small cylinder then show the results formore » a small non-spherical target in three dimensions. We show that the number and magnitudes of the singular values contain information about target composition, shape, and orientation.« less

Distributed MIMO chaotic radar based on wavelength-division multiplexing technology.

PubMed

Yao, Tingfeng; Zhu, Dan; Ben, De; Pan, Shilong

2015-04-15

A distributed multiple-input multiple-output chaotic radar based on wavelength-division multiplexing technology (WDM) is proposed and demonstrated. The wideband quasi-orthogonal chaotic signals generated by different optoelectronic oscillators (OEOs) are emitted by separated antennas to gain spatial diversity against the fluctuation of a target's radar cross section and enhance the detection capability. The received signals collected by the receive antennas and the reference signals from the OEOs are delivered to the central station for joint processing by exploiting WDM technology. The centralized signal processing avoids precise time synchronization of the distributed system and greatly simplifies the remote units, which improves the localization accuracy of the entire system. A proof-of-concept experiment for two-dimensional localization of a metal target is demonstrated. The maximum position error is less than 6.5 cm.

A New Era of Image Guidance with Magnetic Resonance-guided Radiation Therapy for Abdominal and Thoracic Malignancies

PubMed Central

Paliwal, Bhudatt; Hill, Patrick; Bayouth, John E; Geurts, Mark W; Baschnagel, Andrew M; Bradley, Kristin A; Harari, Paul M; Rosenberg, Stephen; Brower, Jeffrey V; Wojcieszynski, Andrzej P; Hullett, Craig; Bayliss, R A; Labby, Zacariah E; Bassetti, Michael F

2018-01-01

Magnetic resonance-guided radiation therapy (MRgRT) offers advantages for image guidance for radiotherapy treatments as compared to conventional computed tomography (CT)-based modalities. The superior soft tissue contrast of magnetic resonance (MR) enables an improved visualization of the gross tumor and adjacent normal tissues in the treatment of abdominal and thoracic malignancies. Online adaptive capabilities, coupled with advanced motion management of real-time tracking of the tumor, directly allow for high-precision inter-/intrafraction localization. The primary aim of this case series is to describe MR-based interventions for localizing targets not well-visualized with conventional image-guided technologies. The abdominal and thoracic sites of the lung, kidney, liver, and gastric targets are described to illustrate the technological advancement of MR-guidance in radiotherapy. PMID:29872602

Image contrast enhancement using adjacent-blocks-based modification for local histogram equalization

NASA Astrophysics Data System (ADS)

Wang, Yang; Pan, Zhibin

2017-11-01

Infrared images usually have some non-ideal characteristics such as weak target-to-background contrast and strong noise. Because of these characteristics, it is necessary to apply the contrast enhancement algorithm to improve the visual quality of infrared images. Histogram equalization (HE) algorithm is a widely used contrast enhancement algorithm due to its effectiveness and simple implementation. But a drawback of HE algorithm is that the local contrast of an image cannot be equally enhanced. Local histogram equalization algorithms are proved to be the effective techniques for local image contrast enhancement. However, over-enhancement of noise and artifacts can be easily found in the local histogram equalization enhanced images. In this paper, a new contrast enhancement technique based on local histogram equalization algorithm is proposed to overcome the drawbacks mentioned above. The input images are segmented into three kinds of overlapped sub-blocks using the gradients of them. To overcome the over-enhancement effect, the histograms of these sub-blocks are then modified by adjacent sub-blocks. We pay more attention to improve the contrast of detail information while the brightness of the flat region in these sub-blocks is well preserved. It will be shown that the proposed algorithm outperforms other related algorithms by enhancing the local contrast without introducing over-enhancement effects and additional noise.

Plastoglobule-Targeting Competence of a Putative Transit Peptide Sequence from Rice Phytoene Synthase 2 in Plastids.

PubMed

You, Min Kyoung; Kim, Jin Hwa; Lee, Yeo Jin; Jeong, Ye Sol; Ha, Sun-Hwa

2016-12-22

Plastoglobules (PGs) are thylakoid membrane microdomains within plastids that are known as specialized locations of carotenogenesis. Three rice phytoene synthase proteins (OsPSYs) involved in carotenoid biosynthesis have been identified. Here, the N-terminal 80-amino-acid portion of OsPSY2 (PTp) was demonstrated to be a chloroplast-targeting peptide by displaying cytosolic localization of OsPSY2(ΔPTp):mCherry in rice protoplast, in contrast to chloroplast localization of OsPSY2:mCherry in a punctate pattern. The peptide sequence of a PTp was predicted to harbor two transmembrane domains eligible for a putative PG-targeting signal. To assess and enhance the PG-targeting ability of PTp, the original PTp DNA sequence ( PTp ) was modified to a synthetic DNA sequence ( stPTp ), which had 84.4% similarity to the original sequence. The motivation of this modification was to reduce the GC ratio from 75% to 65% and to disentangle the hairpin loop structures of PTp . These two DNA sequences were fused to the sequence of the synthetic green fluorescent protein (sGFP) and drove GFP expression with different efficiencies. In particular, the RNA and protein levels of stPTp-sGFP were slightly improved to 1.4-fold and 1.3-fold more than those of sGFP, respectively. The green fluorescent signals of their mature proteins were all observed as speckle-like patterns with slightly blurred stromal signals in chloroplasts. These discrete green speckles of PTp - sGFP and stPTp - sGFP corresponded exactly to the red fluorescent signal displayed by OsPSY2:mCherry in both etiolated and greening protoplasts and it is presumed to correspond to distinct PGs. In conclusion, we identified PTp as a transit peptide sequence facilitating preferential translocation of foreign proteins to PGs, and developed an improved PTp sequence, a s tPTp , which is expected to be very useful for applications in plant biotechnologies requiring precise micro-compartmental localization in plastids.

Temporal Restricted Visual Tracking Via Reverse-Low-Rank Sparse Learning.

PubMed

Yang, Yehui; Hu, Wenrui; Xie, Yuan; Zhang, Wensheng; Zhang, Tianzhu

2017-02-01

An effective representation model, which aims to mine the most meaningful information in the data, plays an important role in visual tracking. Some recent particle-filter-based trackers achieve promising results by introducing the low-rank assumption into the representation model. However, their assumed low-rank structure of candidates limits the robustness when facing severe challenges such as abrupt motion. To avoid the above limitation, we propose a temporal restricted reverse-low-rank learning algorithm for visual tracking with the following advantages: 1) the reverse-low-rank model jointly represents target and background templates via candidates, which exploits the low-rank structure among consecutive target observations and enforces the temporal consistency of target in a global level; 2) the appearance consistency may be broken when target suffers from sudden changes. To overcome this issue, we propose a local constraint via l 1,2 mixed-norm, which can not only ensures the local consistency of target appearance, but also tolerates the sudden changes between two adjacent frames; and 3) to alleviate the inference of unreasonable representation values due to outlier candidates, an adaptive weighted scheme is designed to improve the robustness of the tracker. By evaluating on 26 challenge video sequences, the experiments show the effectiveness and favorable performance of the proposed algorithm against 12 state-of-the-art visual trackers.

In the eye of the stakeholder: The challenges of governing social forest values.

PubMed

Sténs, Anna; Bjärstig, Therese; Nordström, Eva-Maria; Sandström, Camilla; Fries, Clas; Johansson, Johanna

2016-02-01

This study examines which kinds of social benefits derived from forests are emphasised by Swedish stakeholders and what governance modes and management tools they accept. Our study shows that there exists a great variety among stakeholders' perceptions of forests' social values, where tourism and recreation is the most common reference. There are also differences in preferred governance modes and management where biomass and bioenergy sectors advocate business as usual (i.e. framework regulations and voluntarism) and other stakeholders demand rigid tools (i.e. coercion and targeting) and improved landscape planning. This divide will have implications for future policy orientations and require deliberative policy processes and improved dialogue among stakeholders and authorities. We suggest that there is a potential for these improvements, since actors from almost all stakeholder groups support local influence on governance and management, acknowledged and maintained either by the authorities, i.e. targeting, or by the stakeholders themselves, i.e. voluntarism.

Compartmentalization of metabolic pathways in yeast mitochondria improves production of branched chain alcohols

PubMed Central

Avalos, José L.; Fink, Gerald R.; Stephanopoulos, Gregory

2013-01-01

Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeted expression of metabolic pathways to mitochondria can increase production levels compared with expression of the same pathways in the cytoplasm. Compartmentalisation of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overexpressing only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains reveals that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves higher local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion, and reducing the loss of intermediates to competing pathways. PMID:23417095

When being narrow minded is a good thing: locally biased people show stronger contextual cueing.

PubMed

Bellaera, Lauren; von Mühlenen, Adrian; Watson, Derrick G

2014-01-01

Repeated contexts allow us to find relevant information more easily. Learning such contexts has been proposed to depend upon either global processing of the repeated contexts, or alternatively processing of the local region surrounding the target information. In this study, we measured the extent to which observers were by default biased to process towards a more global or local level. The findings showed that the ability to use context to help guide their search was strongly related to an observer's local/global processing bias. Locally biased people could use context to help improve their search better than globally biased people. The results suggest that the extent to which context can be used depends crucially on the observer's attentional bias and thus also to factors and influences that can change this bias.

An infrared small target detection method based on multiscale local homogeneity measure

NASA Astrophysics Data System (ADS)

Nie, Jinyan; Qu, Shaocheng; Wei, Yantao; Zhang, Liming; Deng, Lizhen

2018-05-01

Infrared (IR) small target detection plays an important role in the field of image detection area owing to its intrinsic characteristics. This paper presents a multiscale local homogeneity measure (MLHM) for infrared small target detection, which can enhance the performance of IR small target detection system. Firstly, intra-patch homogeneity of the target itself and the inter-patch heterogeneity between target and the local background regions are integrated to enhance the significant of small target. Secondly, a multiscale measure based on local regions is proposed to obtain the most appropriate response. Finally, an adaptive threshold method is applied to small target segmentation. Experimental results on three different scenarios indicate that the MLHM has good performance under the interference of strong noise.

Use of a Novel Embryonic Mammary Stem Cell Gene Signature to Improve Human Breast Cancer Diagnostics and Therapeutic Decision Making

DTIC Science & Technology

2015-12-01

Our major goals are to determine whether Fetal Mammary Stem Cell (fMaSC) signatures correlate with response to chemotherapy and metastasis in...these aims will enable us to: 1) better categorize distinct cell types within the fMaSC population, 2) identify biomarkers for prospective stem cell purification...and in situ localization, and 3) identify candidate stem cell regulatory pathways that should reveal therapeutic targets and improved

Use of a Novel Embryonic Mammary Stem Cell Gene Signature to Improve Human Breast Cancer Diagnostics and Therapeutic Decision Making

DTIC Science & Technology

2014-10-01

Our major goals are to determine whether Fetal Mammary Stem Cell (fMaSC) signatures correlate with response to chemotherapy and metastasis in...these aims will enable us to: 1) better categorize distinct cell types within the fMaSC population, 2) identify biomarkers for prospective stem cell purification...and in situ localization, and 3) identify candidate stem cell regulatory pathways that should reveal therapeutic targets and improved

Improving the quality of primary care by allocating performance-based targets, in a diverse insured population.

PubMed

Peled, Ronit; Porath, Avi; Wilf-Miron, Rachel

2016-11-21

Primary Care Health organizations, operating under universal coverage and a regulated package of benefits, compete mainly over quality of care. Monitoring, primary care clinical performance, has been repeatedly proven effective in improving the quality of care. In 2004, Maccabi Healthcare Services (MHS), the second largest Israeli HMO, launched its Performance Measurement System (PMS) based on clinical quality indicators. A unique module was built in the PMS to adjust for case mix while tailoring targets to the local units. This article presents the concept and formulas developed to adjust targets to the units' current performance, and analyze change in clinical indicators over a six year period, between sub-population groups. Six process and intermediate outcome indicators, representing screening for breast and colorectal cancer and care for patients with diabetes and cardiovascular disease, were selected and analyzed for change over time (2003-2009) in overall performance, as well as the difference between the lowest and the highest socio-economic ranks (SERs) and Arab and non-Arab members. MHS demonstrated a significant improvement in the selected indicators over the years. Performance of members from low SERs and Arabs improved to a greater extent, as compared to members from high ranks and non-Arabs, respectively. The performance measurement system, with its module for tailoring of units' targets, served as a managerial vehicle for bridging existing gaps by allocating more resources to lower performing units. This concept was proven effective in improving performance while reducing disparities between diverse population groups.

Adaptive non-local means on local principle neighborhood for noise/artifacts reduction in low-dose CT images.

PubMed

Zhang, Yuanke; Lu, Hongbing; Rong, Junyan; Meng, Jing; Shang, Junliang; Ren, Pinghong; Zhang, Junying

2017-09-01

Low-dose CT (LDCT) technique can reduce the x-ray radiation exposure to patients at the cost of degraded images with severe noise and artifacts. Non-local means (NLM) filtering has shown its potential in improving LDCT image quality. However, currently most NLM-based approaches employ a weighted average operation directly on all neighbor pixels with a fixed filtering parameter throughout the NLM filtering process, ignoring the non-stationary noise nature of LDCT images. In this paper, an adaptive NLM filtering scheme on local principle neighborhoods (PC-NLM) is proposed for structure-preserving noise/artifacts reduction in LDCT images. Instead of using neighboring patches directly, in the PC-NLM scheme, the principle component analysis (PCA) is first applied on local neighboring patches of the target patch to decompose the local patches into uncorrelated principle components (PCs), then a NLM filtering is used to regularize each PC of the target patch and finally the regularized components is transformed to get the target patch in image domain. Especially, in the NLM scheme, the filtering parameter is estimated adaptively from local noise level of the neighborhood as well as the signal-to-noise ratio (SNR) of the corresponding PC, which guarantees a "weaker" NLM filtering on PCs with higher SNR and a "stronger" filtering on PCs with lower SNR. The PC-NLM procedure is iteratively performed several times for better removal of the noise and artifacts, and an adaptive iteration strategy is developed to reduce the computational load by determining whether a patch should be processed or not in next round of the PC-NLM filtering. The effectiveness of the presented PC-NLM algorithm is validated by experimental phantom studies and clinical studies. The results show that it can achieve promising gain over some state-of-the-art methods in terms of artifact suppression and structure preservation. With the use of PCA on local neighborhoods to extract principal structural components, as well as adaptive NLM filtering on PCs of the target patch using filtering parameter estimated based on the local noise level and corresponding SNR, the proposed PC-NLM method shows its efficacy in preserving fine anatomical structures and suppressing noise/artifacts in LDCT images. © 2017 American Association of Physicists in Medicine.

34 CFR 200.88 - Exclusion of supplemental State and local funds from supplement, not supplant and comparability...

Code of Federal Regulations, 2011 CFR

2011-07-01

... EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Migrant Education Program § 200.88... migratory children, as defined in section 1309 of the ESEA. (2) The program is based on performance targets... these requirements. (4) The grantee monitors program performance to ensure that these requirements are...

MRI-guided brachytherapy

PubMed Central

Tanderup, Kari; Viswanathan, Akila; Kirisits, Christian; Frank, Steven J.

2014-01-01

The application of MRI-guided brachytherapy has demonstrated significant growth during the last two decades. Clinical improvements in cervix cancer outcomes have been linked to the application of repeated MRI for identification of residual tumor volumes during radiotherapy. This has changed clinical practice in the direction of individualized dose administration, and mounting evidence of improved clinical outcome with regard to local control, overall survival as well as morbidity. MRI-guided prostate HDR and LDR brachytherapy has improved the accuracy of target and organs-at-risk (OAR) delineation, and the potential exists for improved dose prescription and reporting for the prostate gland and organs at risk. Furthermore, MRI-guided prostate brachytherapy has significant potential to identify prostate subvolumes and dominant lesions to allow for dose administration reflecting the differential risk of recurrence. MRI-guided brachytherapy involves advanced imaging, target concepts, and dose planning. The key issue for safe dissemination and implementation of high quality MRI-guided brachytherapy is establishment of qualified multidisciplinary teams and strategies for training and education. PMID:24931089

Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization.

PubMed

Perera, Yasser; Costales, Heydi C; Diaz, Yakelin; Reyes, Osvaldo; Farina, Hernan G; Mendez, Lissandra; Gómez, Roberto E; Acevedo, Boris E; Gomez, Daniel E; Alonso, Daniel F; Perea, Silvio E

2012-04-01

CIGB-300 is a novel anticancer peptide that impairs the casein kinase 2-mediated phosphorylation by direct binding to the conserved phosphoacceptor site on their substrates. Previous findings indicated that CIGB-300 inhibits tumor cell proliferation in vitro and induces tumor growth delay in vivo in cancer animal models. Interestingly, we had previously demonstrated that the putative oncogene B23/nucleophosmin (NPM) is the major intracellular target for CIGB-300 in a sensitive human lung cancer cell line. However, the ability of this peptide to target B23/NPM in cancer cells with differential CIGB-300 response phenotype remained to be determined. Interestingly, in this work, we evidenced that CIGB-300's antiproliferative activity on tumor cells strongly correlates with its nucleolar localization, the main subcellular localization of the previously identified B23/NPM target. Likewise, using CIGB-300 equipotent doses (concentration that inhibits 50% of proliferation), we demonstrated that this peptide interacts and inhibits B23/NPM phosphorylation in different cancer cell lines as evidenced by in vivo pull-down and metabolic labeling experiments. Moreover, such inhibition was followed by a fast apoptosis on CIGB-300-treated cells and also an impairment of cell cycle progression mainly after 5 h of treatment. Altogether, our data not only validates B23/NPM as a main target for CIGB-300 in cancer cells but also provides the first experimental clues to explain their differential antiproliferative response. Importantly, our findings suggest that further improvements to this cell penetrating peptide-based drug should entail its more efficient intracellular delivery at such subcellular localization. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

All purulence is local – epidemiology and management of skin and soft tissue infections in three urban emergency departments

PubMed Central

2013-01-01

Background Skin and soft tissue infection (SSTIs) are commonly treated in emergency departments (EDs). While the precise role of antibiotics in treating SSTIs remains unclear, most SSTI patients receive empiric antibiotics, often targeted toward methicillin-resistant Staphylococcus aureus (MRSA). The goal of this study was to assess the efficiency with which ED clinicians targeted empiric therapy against MRSA, and to identify factors that may allow ED clinicians to safely target antibiotic use. Methods We performed a retrospective analysis of patient visits for community-acquired SSTIs to three urban, academic EDs in one northeastern US city during the first quarter of 2010. We examined microbiologic patterns among cultured SSTIs, and relationships between clinical and demographic factors and management of SSTIs. Results Antibiotics were prescribed to 86.1% of all patients. Though S. aureus (60% MRSA) was the most common pathogen cultured, antibiotic susceptibility differed between adult and pediatric patients. Susceptibility of S. aureus from ED SSTIs differed from published local antibiograms, with greater trimethoprim resistance and less fluoroquinolone resistance than seen in S. aureus from all hospital sources. Empiric antibiotics covered the resultant pathogen in 85.3% of cases, though coverage was frequently broader than necessary. Conclusions Though S. aureus remained the predominant pathogen in community-acquired SSTIs, ED clinicians did not accurately target therapy toward the causative pathogen. Incomplete local epidemiologic data may contribute to this degree of discordance. Future efforts should seek to identify when antibiotic use can be narrowed or withheld. Local, disease-specific antibiotic resistance patterns should be publicized with the goal of improving antibiotic stewardship. PMID:24359038

Fusion-based multi-target tracking and localization for intelligent surveillance systems

NASA Astrophysics Data System (ADS)

Rababaah, Haroun; Shirkhodaie, Amir

2008-04-01

In this paper, we have presented two approaches addressing visual target tracking and localization in complex urban environment. The two techniques presented in this paper are: fusion-based multi-target visual tracking, and multi-target localization via camera calibration. For multi-target tracking, the data fusion concepts of hypothesis generation/evaluation/selection, target-to-target registration, and association are employed. An association matrix is implemented using RGB histograms for associated tracking of multi-targets of interests. Motion segmentation of targets of interest (TOI) from the background was achieved by a Gaussian Mixture Model. Foreground segmentation, on other hand, was achieved by the Connected Components Analysis (CCA) technique. The tracking of individual targets was estimated by fusing two sources of information, the centroid with the spatial gating, and the RGB histogram association matrix. The localization problem is addressed through an effective camera calibration technique using edge modeling for grid mapping (EMGM). A two-stage image pixel to world coordinates mapping technique is introduced that performs coarse and fine location estimation of moving TOIs. In coarse estimation, an approximate neighborhood of the target position is estimated based on nearest 4-neighbor method, and in fine estimation, we use Euclidean interpolation to localize the position within the estimated four neighbors. Both techniques were tested and shown reliable results for tracking and localization of Targets of interests in complex urban environment.

Sounds Activate Visual Cortex and Improve Visual Discrimination

PubMed Central

Störmer, Viola S.; Martinez, Antigona; McDonald, John J.; Hillyard, Steven A.

2014-01-01

A recent study in humans (McDonald et al., 2013) found that peripheral, task-irrelevant sounds activated contralateral visual cortex automatically as revealed by an auditory-evoked contralateral occipital positivity (ACOP) recorded from the scalp. The present study investigated the functional significance of this cross-modal activation of visual cortex, in particular whether the sound-evoked ACOP is predictive of improved perceptual processing of a subsequent visual target. A trial-by-trial analysis showed that the ACOP amplitude was markedly larger preceding correct than incorrect pattern discriminations of visual targets that were colocalized with the preceding sound. Dipole modeling of the scalp topography of the ACOP localized its neural generators to the ventrolateral extrastriate visual cortex. These results provide direct evidence that the cross-modal activation of contralateral visual cortex by a spatially nonpredictive but salient sound facilitates the discriminative processing of a subsequent visual target event at the location of the sound. Recordings of event-related potentials to the targets support the hypothesis that the ACOP is a neural consequence of the automatic orienting of visual attention to the location of the sound. PMID:25031419

A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells.

PubMed

Glaffig, Markus; Stergiou, Natascha; Hartmann, Sebastian; Schmitt, Edgar; Kunz, Horst

2018-01-08

A MUC1 anticancer vaccine equipped with covalently linked divalent mannose ligands was found to improve the antigen uptake and presentation by targeting mannose-receptor-positive macrophages and dendritic cells. It induced much stronger specific IgG immune responses in mice than the non-mannosylated reference vaccine. Mannose coupling also led to increased numbers of macrophages, dendritic cells, and CD4 + T cells in the local lymph organs. Comparison of di- and tetravalent mannose ligands revealed an increased binding of the tetravalent version, suggesting that higher valency improves binding to the mannose receptor. The mannose-coupled vaccine and the non-mannosylated reference vaccine induced IgG antibodies that exhibited similar binding to human breast tumor cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The “Long Tail” and Public Health: New Thinking for Addressing Health Disparities

PubMed Central

Hovmand, Peter; Pfeiffer, Debbie J.; Fairchild, Maggie; Rath, Suchitra; Golla, Balaji; Casey, Chris

2014-01-01

The prevailing approach to improving population health focuses on shifting population means through a few targeted and universal interventions. The success of this approach for eliminating health disparities depends on an assumption about the distribution of demand for such interventions. We explored whether long tail thinking from business might yield greater progress in eliminating disparities. We examined 2011 to 2013 data from 513 state and local health agency representatives in 47 states who used an online system to create 4351 small media and client reminder products promoting colorectal cancer screening. Products in the long tail were more likely to target minority groups with higher rates of colorectal cancer and lower rates of screening than Whites. Long tail thinking could help improve the public's health and eliminate disparities. PMID:25322308

Should the Centers for Disease Control and Prevention's childhood lead poisoning intervention level be lowered?

PubMed

Bernard, Susan M

2003-08-01

The US Centers for Disease Control and Prevention (CDC) in 1991 chose 10 micro g/dL as an initial screening level for lead in children's blood. Current data on health risks and intervention options do not support generally lowering that level, but federal lead poisoning prevention efforts can be improved by revising the follow-up testing schedule for infants aged 1 year or less with blood lead levels of 5 micro g/dL or higher; universal education about lead exposure risks; universal administration of improved, locally validated risk-screening questionnaires; enhanced compliance with targeted screening recommendations and federal health program requirements; and development by regulatory agencies of primary prevention criteria that do not use the CDC's intervention level as a target "safe" lead exposure.

Algorithm for Automatic Detection, Localization and Characterization of Magnetic Dipole Targets Using the Laser Scalar Gradiometer

DTIC Science & Technology

2016-06-01

TECHNICAL REPORT Algorithm for Automatic Detection, Localization and Characterization of Magnetic Dipole Targets Using the Laser Scalar...Automatic Detection, Localization and Characterization of Magnetic Dipole Targets Using the Laser Scalar Gradiometer Leon Vaizer, Jesse Angle, Neil...of Magnetic Dipole Targets Using LSG i June 2016 TABLE OF CONTENTS INTRODUCTION

Testing neuropsychological hypotheses for cognitive deficits in psychopathic criminals: a study of global-local processing.

PubMed

Kosson, David S; Miller, Sarah K; Byrnes, Katherine A; Leveroni, Catherine L

2007-03-01

Competing hypotheses about neuropsychological mechanisms underlying psychopathy are seldom examined in the same study. We tested the left hemisphere activation hypothesis and the response modulation hypothesis of psychopathy in 172 inmates completing a global-local processing task under local bias, global bias, and neutral conditions. Consistent with the left hemisphere activation hypothesis, planned comparisons showed that psychopathic inmates classified local targets more slowly than nonpsychopathic inmates in a local bias condition and exhibited a trend toward similar deficits for global targets in this condition. However, contrary to the response modulation hypothesis, psychopaths were no slower to respond to local targets in a global bias condition. Because psychopathic inmates were not generally slower to respond to local targets, results are also not consistent with a general left hemisphere dysfunction account. Correlational analyses also indicated deficits specific to conditions presenting most targets at the local level initially. Implications for neuropsychological conceptualizations of psychopathy are considered.

Apparatus, Method and Program Storage Device for Determining High-Energy Neutron/Ion Transport to a Target of Interest

NASA Technical Reports Server (NTRS)

Wilson, John W. (Inventor); Tripathi, Ram K. (Inventor); Cucinotta, Francis A. (Inventor); Badavi, Francis F. (Inventor)

2012-01-01

An apparatus, method and program storage device for determining high-energy neutron/ion transport to a target of interest. Boundaries are defined for calculation of a high-energy neutron/ion transport to a target of interest; the high-energy neutron/ion transport to the target of interest is calculated using numerical procedures selected to reduce local truncation error by including higher order terms and to allow absolute control of propagated error by ensuring truncation error is third order in step size, and using scaling procedures for flux coupling terms modified to improve computed results by adding a scaling factor to terms describing production of j-particles from collisions of k-particles; and the calculated high-energy neutron/ion transport is provided to modeling modules to control an effective radiation dose at the target of interest.

Monitoring and evaluation of disaster response efforts undertaken by local health departments: a rapid realist review.

PubMed

Gossip, Kate; Gouda, Hebe; Lee, Yong Yi; Firth, Sonja; Bermejo, Raoul; Zeck, Willibald; Jimenez Soto, Eliana

2017-06-29

Local health departments are often at the forefront of a disaster response, attending to the immediate trauma inflicted by the disaster and also the long term health consequences. As the frequency and severity of disasters are projected to rise, monitoring and evaluation (M&E) efforts are critical to help local health departments consolidate past experiences and improve future response efforts. Local health departments often conduct M&E work post disaster, however, many of these efforts fail to improve response procedures. We undertook a rapid realist review (RRR) to examine why M&E efforts undertaken by local health departments do not always result in improved disaster response efforts. We aimed to complement existing frameworks by focusing on the most basic and pragmatic steps of a M&E cycle targeted towards continuous system improvements. For these purposes, we developed a theoretical framework that draws on the quality improvement literature to 'frame' the steps in the M&E cycle. This framework encompassed a M&E cycle involving three stages (i.e., document and assess, disseminate and implement) that must be sequentially completed to learn from past experiences and improve future disaster response efforts. We used this framework to guide our examination of the literature and to identify any context-mechanism-outcome (CMO) configurations which describe how M&E may be constrained or enabled at each stage of the M&E cycle. This RRR found a number of explanatory CMO configurations that provide valuable insights into some of the considerations that should be made when using M&E to improve future disaster response efforts. Firstly, to support the accurate documentation and assessment of a disaster response, local health departments should consider how they can: establish a culture of learning within health departments; use embedded training methods; or facilitate external partnerships. Secondly, to enhance the widespread dissemination of lessons learned and facilitate inter-agency learning, evaluation reports should use standardised formats and terminology. Lastly, to increase commitment to improvement processes, local health department leaders should possess positive leadership attributes and encourage shared decision making. This study is among the first to conduct a synthesis of the CMO configurations which facilitate or hinder M&E efforts aimed at improving future disaster responses. It makes a significant contribution to the disaster literature and provides an evidence base that can be used to provide pragmatic guidance for improving M&E efforts of local health departments. PROSPERO 2015: CRD42015023526 .

Reducing intraoperative red blood cell unit wastage in a large academic medical center.

PubMed

Whitney, Gina M; Woods, Marcella C; France, Daniel J; Austin, Thomas M; Deegan, Robert J; Paroskie, Allison; Booth, Garrett S; Young, Pampee P; Dmochowski, Roger R; Sandberg, Warren S; Pilla, Michael A

2015-11-01

The wastage of red blood cell (RBC) units within the operative setting results in significant direct costs to health care organizations. Previous education-based efforts to reduce wastage were unsuccessful at our institution. We hypothesized that a quality and process improvement approach would result in sustained reductions in intraoperative RBC wastage in a large academic medical center. Utilizing a failure mode and effects analysis supplemented with time and temperature data, key drivers of perioperative RBC wastage were identified and targeted for process improvement. Multiple contributing factors, including improper storage and transport and lack of accurate, locally relevant RBC wastage event data were identified as significant contributors to ongoing intraoperative RBC unit wastage. Testing and implementation of improvements to the process of transport and storage of RBC units occurred in liver transplant and adult cardiac surgical areas due to their history of disproportionately high RBC wastage rates. Process interventions targeting local drivers of RBC wastage resulted in a significant reduction in RBC wastage (p < 0.0001; adjusted odds ratio, 0.24; 95% confidence interval, 0.15-0.39), despite an increase in operative case volume over the period of the study. Studied process interventions were then introduced incrementally in the remainder of the perioperative areas. These results show that a multidisciplinary team focused on the process of blood product ordering, transport, and storage was able to significantly reduce operative RBC wastage and its associated costs using quality and process improvement methods. © 2015 AABB.

Reducing intraoperative red blood cell unit wastage in a large academic medical center

PubMed Central

Whitney, Gina M.; Woods, Marcella C.; France, Daniel J.; Austin, Thomas M.; Deegan, Robert J.; Paroskie, Allison; Booth, Garrett S.; Young, Pampee P.; Dmochowski, Roger R.; Sandberg, Warren S.; Pilla, Michael A.

2015-01-01

BACKGROUND The wastage of red blood cell (RBC) units within the operative setting results in significant direct costs to health care organizations. Previous education-based efforts to reduce wastage were unsuccessful at our institution. We hypothesized that a quality and process improvement approach would result in sustained reductions in intraoperative RBC wastage in a large academic medical center. STUDY DESIGN AND METHODS Utilizing a failure mode and effects analysis supplemented with time and temperature data, key drivers of perioperative RBC wastage were identified and targeted for process improvement. RESULTS Multiple contributing factors, including improper storage and transport and lack of accurate, locally relevant RBC wastage event data were identified as significant contributors to ongoing intraoperative RBC unit wastage. Testing and implementation of improvements to the process of transport and storage of RBC units occurred in liver transplant and adult cardiac surgical areas due to their history of disproportionately high RBC wastage rates. Process interventions targeting local drivers of RBC wastage resulted in a significant reduction in RBC wastage (p <0.0001; adjusted odds ratio, 0.24; 95% confidence interval, 0.15–0.39), despite an increase in operative case volume over the period of the study. Studied process interventions were then introduced incrementally in the remainder of the perioperative areas. CONCLUSIONS These results show that a multidisciplinary team focused on the process of blood product ordering, transport, and storage was able to significantly reduce operative RBC wastage and its associated costs using quality and process improvement methods. PMID:26202213

Bilateral Versus Unilateral Cochlear Implantation in Adult Listeners: Speech-On-Speech Masking and Multitalker Localization.

PubMed

Rana, Baljeet; Buchholz, Jörg M; Morgan, Catherine; Sharma, Mridula; Weller, Tobias; Konganda, Shivali Appaiah; Shirai, Kyoko; Kawano, Atsushi

2017-01-01

Binaural hearing helps normal-hearing listeners localize sound sources and understand speech in noise. However, it is not fully understood how far this is the case for bilateral cochlear implant (CI) users. To determine the potential benefits of bilateral over unilateral CIs, speech comprehension thresholds (SCTs) were measured in seven Japanese bilateral CI recipients using Helen test sentences (translated into Japanese) in a two-talker speech interferer presented from the front (co-located with the target speech), ipsilateral to the first-implanted ear (at +90° or -90°), and spatially symmetric at ±90°. Spatial release from masking was calculated as the difference between co-located and spatially separated SCTs. Localization was assessed in the horizontal plane by presenting either male or female speech or both simultaneously. All measurements were performed bilaterally and unilaterally (with the first implanted ear) inside a loudspeaker array. Both SCTs and spatial release from masking were improved with bilateral CIs, demonstrating mean bilateral benefits of 7.5 dB in spatially asymmetric and 3 dB in spatially symmetric speech mixture. Localization performance varied strongly between subjects but was clearly improved with bilateral over unilateral CIs with the mean localization error reduced by 27°. Surprisingly, adding a second talker had only a negligible effect on localization.

Beamforming using subspace estimation from a diagonally averaged sample covariance.

PubMed

Quijano, Jorge E; Zurk, Lisa M

2017-08-01

The potential benefit of a large-aperture sonar array for high resolution target localization is often challenged by the lack of sufficient data required for adaptive beamforming. This paper introduces a Toeplitz-constrained estimator of the clairvoyant signal covariance matrix corresponding to multiple far-field targets embedded in background isotropic noise. The estimator is obtained by averaging along subdiagonals of the sample covariance matrix, followed by covariance extrapolation using the method of maximum entropy. The sample covariance is computed from limited data snapshots, a situation commonly encountered with large-aperture arrays in environments characterized by short periods of local stationarity. Eigenvectors computed from the Toeplitz-constrained covariance are used to construct signal-subspace projector matrices, which are shown to reduce background noise and improve detection of closely spaced targets when applied to subspace beamforming. Monte Carlo simulations corresponding to increasing array aperture suggest convergence of the proposed projector to the clairvoyant signal projector, thereby outperforming the classic projector obtained from the sample eigenvectors. Beamforming performance of the proposed method is analyzed using simulated data, as well as experimental data from the Shallow Water Array Performance experiment.

Mitochondria-targeted cationic porphyrin-triphenylamine hybrids for enhanced two-photon photodynamic therapy.

PubMed

Hammerer, Fabien; Poyer, Florent; Fourmois, Laura; Chen, Su; Garcia, Guillaume; Teulade-Fichou, Marie-Paule; Maillard, Philippe; Mahuteau-Betzer, Florence

2018-01-01

The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protecting children from harmful food marketing: options for local government to make a difference.

PubMed

Harris, Jennifer L; Graff, Samantha K

2011-09-01

The obesity epidemic cannot be reversed without substantial improvements in the food marketing environment that surrounds children. Food marketing targeted to children almost exclusively promotes calorie-dense, nutrient-poor foods and takes advantage of children's vulnerability to persuasive messages. Increasing scientific evidence reveals potentially profound effects of food marketing on children's lifelong eating behaviors and health. Much of this marketing occurs in nationwide media (eg, television, the Internet), but companies also directly target children in their own communities through the use of billboards and through local environments such as stores, restaurants, and schools. Given the harmful effect of this marketing environment on children's health and the industry's reluctance to make necessary changes to its food marketing practices, government at all levels has an obligation to act. This article focuses on policy options for municipalities that are seeking ways to limit harmful food marketing at the community level.

Recent advances in radiation cancer therapy

NASA Astrophysics Data System (ADS)

Ma, C.-M. Charlie

2007-03-01

This paper presents the recent advances in radiation therapy techniques for the treatment of cancer. Significant improvement has been made in imaging techniques such as CT, MRI, MRS, PET, ultrasound, etc. that have brought marked advances in tumor target and critical structure delineation for treatment planning and patient setup and target localization for accurate dose delivery in radiation therapy of cancer. Recent developments of novel treatment modalities including intensity-modulated x-ray therapy (IMXT), energy- and intensity modulated electron therapy (MERT) and intensity modulated proton therapy (IMPT) together with the use of advanced image guidance have enabled precise dose delivery for dose escalation and hypofractionation studies that may result in better local control and quality of life. Particle acceleration using laser-induced plasmas has great potential for new cost-effective radiation sources that may have a great impact on the management of cancer using radiation therapy.

Augmented Reality Tool for the Situational Awareness Improvement of UAV Operators

PubMed Central

Ruano, Susana; Cuevas, Carlos; Gallego, Guillermo; García, Narciso

2017-01-01

Unmanned Aerial Vehicles (UAVs) are being extensively used nowadays. Therefore, pilots of traditional aerial platforms should adapt their skills to operate them from a Ground Control Station (GCS). Common GCSs provide information in separate screens: one presents the video stream while the other displays information about the mission plan and information coming from other sensors. To avoid the burden of fusing information displayed in the two screens, an Augmented Reality (AR) tool is proposed in this paper. The AR system has two functionalities for Medium-Altitude Long-Endurance (MALE) UAVs: route orientation and target identification. Route orientation allows the operator to identify the upcoming waypoints and the path that the UAV is going to follow. Target identification allows a fast target localization, even in the presence of occlusions. The AR tool is implemented following the North Atlantic Treaty Organization (NATO) standards so that it can be used in different GCSs. The experiments show how the AR tool improves significantly the situational awareness of the UAV operators. PMID:28178189

Augmented Reality Tool for the Situational Awareness Improvement of UAV Operators.

PubMed

Ruano, Susana; Cuevas, Carlos; Gallego, Guillermo; García, Narciso

2017-02-06

Unmanned Aerial Vehicles (UAVs) are being extensively used nowadays. Therefore, pilots of traditional aerial platforms should adapt their skills to operate them from a Ground Control Station (GCS). Common GCSs provide information in separate screens: one presents the video stream while the other displays information about the mission plan and information coming from other sensors. To avoid the burden of fusing information displayed in the two screens, an Augmented Reality (AR) tool is proposed in this paper. The AR system has two functionalities for Medium-Altitude Long-Endurance (MALE) UAVs: route orientation and target identification. Route orientation allows the operator to identify the upcoming waypoints and the path that the UAV is going to follow. Target identification allows a fast target localization, even in the presence of occlusions. The AR tool is implemented following the North Atlantic Treaty Organization (NATO) standards so that it can be used in different GCSs. The experiments show how the AR tool improves significantly the situational awareness of the UAV operators.

[C-terminal lysosome targeting domain of CD63 modifies cellular localization of rabies virus glycoprotein].

PubMed

Starodubova, E S; Kuzmenko, Y V; Latanova, A A; Preobrazhenskaya, O V; Karpov, V L

2017-01-01

The glycoprotein of rabies virus is the central antigen elicited the immune response to infection; therefore, the majority of developing anti-rabies vaccines are based on this protein. In order to increase the efficacy of DNA immunogen encoding rabies virus glycoprotein, the construction of chimeric protein with the CD63 domain has been proposed. The CD63 is a transmembrane protein localized on the cell surface and in lysosomes. The lysosome targeting motif GYEVM is located at its C-terminus. We used the domain that bears this motif (c-CD63) to generate chimeric glycoprotein in order to relocalize it into lysosomes. Here, it was shown that, in cells transfected with plasmid that encodes glycoprotein with c-CD63 motif at the C-terminus, the chimeric protein was predominantly observed in lysosomes and at the cell membrane where the unmodified glycoprotein is localized in the endoplasmic reticulum and at the cell surface. We suppose that current modification of the glycoprotein may improve the immunogenicity of anti-rabies DNA vaccines due to more efficient antibody production.

Nuclear Localizing Peptide-Conjugated, Redox-Sensitive Polymersomes for Delivering Curcumin and Doxorubicin to Pancreatic Cancer Microtumors.

PubMed

Anajafi, Tayebeh; Yu, Junru; Sedigh, Abbas; Haldar, Manas K; Muhonen, Wallace W; Oberlander, Seth; Wasness, Heather; Froberg, Jamie; Molla, Md Shahjahan; Katti, Kalpana S; Choi, Yongki; Shabb, John B; Srivastava, D K; Mallik, Sanku

2017-06-05

Improving the therapeutic index of anticancer agents is an enormous challenge. Targeting decreases the side effects of the therapeutic agents by delivering the drugs to the intended destination. Nanocarriers containing the nuclear localizing peptide sequences (NLS) translocate to the cell nuclei. However, the nuclear localization peptides are nonselective and cannot distinguish the malignant cells from the healthy counterparts. In this study, we designed a "masked" NLS peptide which is activated only in the presence of overexpressed matrix metalloproteinase-7 (MMP-7) enzyme in the pancreatic cancer microenvironment. This peptide is conjugated to the surface of redox responsive polymersomes to deliver doxorubicin and curcumin to the pancreatic cancer cell nucleus. We have tested the formulation in both two- and three-dimensional cultures of pancreatic cancer and normal cells. Our studies revealed that the drug-encapsulated polymeric vesicles are significantly more toxic toward the cancer cells (shrinking the spheroids up to 49%) compared to the normal cells (shrinking the spheroids up to 24%). This study can lead to the development of other organelle targeted drug delivery systems for various human malignancies.

Increasing walking at the C&O Canal National Historical Park: an intervention focused on local employees

Treesearch

Dave Smaldone

2009-01-01

This study sought to increase walking in the C&O Canal National Historical Park (NHP). C&O Canal NHP joined with Georgetown University, George Washington University, and the Georgetown Business Improvement District to target the employees of these businesses. The study was very similar to a multi-worksite employee wellness research program. Volunteer...

National Tests in Denmark--CAT as a Pedagogic Tool

ERIC Educational Resources Information Center

Wandall, Jakob

2011-01-01

Testing and test results can be used in different ways. They can be used for regulation and control, but they can also be a pedagogic tool for assessment of student proficiency in order to target teaching, improve learning and facilitate local pedagogical leadership. To serve these purposes the test has to be used for low stakes purposes, and to…

DOA Estimation for Underwater Wideband Weak Targets Based on Coherent Signal Subspace and Compressed Sensing.

PubMed

Li, Jun; Lin, Qiu-Hua; Kang, Chun-Yu; Wang, Kai; Yang, Xiu-Ting

2018-03-18

Direction of arrival (DOA) estimation is the basis for underwater target localization and tracking using towed line array sonar devices. A method of DOA estimation for underwater wideband weak targets based on coherent signal subspace (CSS) processing and compressed sensing (CS) theory is proposed. Under the CSS processing framework, wideband frequency focusing is accompanied by a two-sided correlation transformation, allowing the DOA of underwater wideband targets to be estimated based on the spatial sparsity of the targets and the compressed sensing reconstruction algorithm. Through analysis and processing of simulation data and marine trial data, it is shown that this method can accomplish the DOA estimation of underwater wideband weak targets. Results also show that this method can considerably improve the spatial spectrum of weak target signals, enhancing the ability to detect them. It can solve the problems of low directional resolution and unreliable weak-target detection in traditional beamforming technology. Compared with the conventional minimum variance distortionless response beamformers (MVDR), this method has many advantages, such as higher directional resolution, wider detection range, fewer required snapshots and more accurate detection for weak targets.

A research agenda for malaria eradication: vector control.

PubMed

2011-01-25

Different challenges are presented by the variety of malaria transmission environments present in the world today. In each setting, improved control for reduction of morbidity is a necessary first step towards the long-range goal of malaria eradication and a priority for regions where the disease burden is high. For many geographic areas where transmission rates are low to moderate, sustained and well-managed application of currently available tools may be sufficient to achieve local elimination. The research needs for these areas will be to sustain and perhaps improve the effectiveness of currently available tools. For other low-to-moderate transmission regions, notably areas where the vectors exhibit behaviours such as outdoor feeding and resting that are not well targeted by current strategies, new interventions that target predictable features of the biology/ecologies of the local vectors will be required. To achieve elimination in areas where high levels of transmission are sustained by very efficient vector species, radically new interventions that significantly reduce the vectorial capacity of wild populations will be needed. Ideally, such interventions should be implemented with a one-time application with a long-lasting impact, such as genetic modification of the vectorial capacity of the wild vector population.

Maria Auxiliadora Hospital in Lima, Peru as a model for neurosurgical outreach to international charity hospitals.

PubMed

Hayden, Melanie G; Hughes, Samuel; Hahn, Edward J; Aryan, Henry E; Levy, Michael L; Jandial, Rahul

2011-01-01

A myriad of geopolitical and financial obstacles have kept modern neurosurgery from effectively reaching the citizens of the developing world. Targeted neurosurgical outreach by academic neurosurgeons to equip neurosurgical operating theaters and train local neurosurgeons is one method to efficiently and cost effectively improve sustainable care provided by international charity hospitals. The International Neurosurgical Children's Association (INCA) effectively improved the available neurosurgical care in the Maria Auxiliadora Hospital of Lima, Peru through the advancement of local specialist education and training. Neurosurgical equipment and training were provided for the local neurosurgeons by a mission team from the University of California at San Diego. At the end of 3 years, with one intensive week trip per year, the host neurosurgeons were proficiently and independently applying microsurgical techniques to previously performed operations, and performing newly learned operations such as neuroendoscopy and minimally invasive neurosurgery. Our experiences may serve as a successful template for the execution of other small scale, sustainable neurosurgery missions worldwide.

Working memory load can both improve and impair selective attention: evidence from the Navon paradigm.

PubMed

Ahmed, Lubna; de Fockert, Jan W

2012-10-01

Selective attention to relevant targets has been shown to depend on the availability of working memory (WM). Under conditions of high WM load, processing of irrelevant distractors is enhanced. Here we showed that this detrimental effect of WM load on selective attention efficiency is reversed when the task requires global- rather than local-level processing. Participants were asked to attend to either the local or the global level of a hierarchical Navon stimulus while keeping either a low or a high load in WM. In line with previous findings, during attention to the local level, distractors at the global level produced more interference under high than under low WM load. By contrast, loading WM had the opposite effect of improving selective attention during attention to the global level. The findings demonstrate that the impact of WM load on selective attention is not invariant, but rather is dependent on the level of the to-be-attended information.

The influence of participation in target-shooting sport for children with inattentive, hyperactive and impulsive symptoms - A controlled study of best practice.

PubMed

Månsson, Annegrete Gohr; Elmose, Mette; Dalsgaard, Søren; Roessler, Kirsten K

2017-03-28

Practising target-shooting sport requires focused attention and motoric steadiness. A previous non-controlled pilot study suggests that children with impairing symptoms of attention-deficit/hyperactivity disorder (ADHD) benefit from participating in target-shooting sport in local shooting associations, as rated by parents and teachers. This study aims at examining if, and to which extent, target-shooting sport reduces parent- and teacher-reported severity of inattentiveness, hyperactivity, and impulsivity in children with attention difficulties, and if, and to which extend, target-shooting sport improves the children's wellbeing and quality of life. A mixed method approach is applied. A non-blinded, waiting list controlled study is combined with a case study, consisting of interviews and observations. The intervention consists of children practising target-shooting sport, by attending a local shooting association, once a week for six months, during regular school hours. Data from questionnaires (ADHD-RS, SDQ, Kidscreen-27), as well as a computerized continued performance test (Qb test), measure the children's activity and attention. The study includes 50 children in an intervention group and 50 children in a waiting list control group. The Qb test collects data from at least 20 children from the intervention group and at least 20 children from the waiting list control group. Data from the questionnaires and Qb-test is collected at baseline, and six months post intervention. In addition, a case study is carried out, consisting of interviews of at least five children from the intervention group, their parents, teachers and shooting instructors. Observations are carried out, when children are in school and while they are attending the local shooting association. The case study adds to an in-depth understanding of children's participation in target-shooting sports. At present, little is known about the effects and influence of practising target-shooting sport for children experiencing difficulties with inattentiveness, hyperactivity and impulsivity. This study is expected to contribute to an understanding of the influence of participating in target-shooting sports on inattentive, hyperactive and impulsive symptoms, and the effects on the children's psychological wellbeing and quality of life. Current Controlled Trials NCT02898532 . Retrospectively registered 14 September 2016.

Magnetic nanoparticles as potential candidates for biomedical and biological applications.

PubMed

Zeinali Sehrig, Fatemeh; Majidi, Sima; Nikzamir, Nasrin; Nikzamir, Nasim; Nikzamir, Mohammad; Akbarzadeh, Abolfazl

2016-05-01

Magnetic iron oxide nanoparticles have become the main candidates for biomedical and biological applications, and the application of small iron oxide nanoparticles in in vitro diagnostics has been practiced for about half a century. Magnetic nanoparticles (MNPs), in combination with an external magnetic field and/or magnetizable grafts, allow the delivery of particles to the chosen target area, fix them at the local site while the medication is released, and act locally. In this review, we focus mostly on the potential use of MNPs for biomedical and biotechnological applications, and the improvements made in using these nanoparticles (NPs) in biological applications.

Recent advances in understanding and managing chordomas.

PubMed

Youssef, Carl; Aoun, Salah G; Moreno, Jessica R; Bagley, Carlos A

2016-01-01

Chordomas are rare primary bone tumors arising from embryonic remnants of the notochord. They are slow-growing, locally aggressive, and destructive and typically involve the axial skeleton. Genetic studies have identified several mutations implicated in the pathogenesis of these tumors. Treatment poses a challenge given their insidious progression, degree of local invasion at presentation, and high recurrence rate. They tend to respond poorly to conventional chemotherapy and radiation. This makes radical resection the mainstay of their treatment. Recent advances in targeted chemotherapy and focused particle beam radiation, however, have improved the management and prognosis of these tumors.

Generation and evaluation of an ultra-high-field atlas with applications in DBS planning

NASA Astrophysics Data System (ADS)

Wang, Brian T.; Poirier, Stefan; Guo, Ting; Parrent, Andrew G.; Peters, Terry M.; Khan, Ali R.

2016-03-01

Purpose Deep brain stimulation (DBS) is a common treatment for Parkinson's disease (PD) and involves the use of brain atlases or intrinsic landmarks to estimate the location of target deep brain structures, such as the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi). However, these structures can be difficult to localize with conventional clinical magnetic resonance imaging (MRI), and thus targeting can be prone to error. Ultra-high-field imaging at 7T has the ability to clearly resolve these structures and thus atlases built with these data have the potential to improve targeting accuracy. Methods T1 and T2-weighted images of 12 healthy control subjects were acquired using a 7T MR scanner. These images were then used with groupwise registration to generate an unbiased average template with T1w and T2w contrast. Deep brain structures were manually labelled in each subject by two raters and rater reliability was assessed. We compared the use of this unbiased atlas with two other methods of atlas-based segmentation (single-template and multi-template) for subthalamic nucleus (STN) segmentation on 7T MRI data. We also applied this atlas to clinical DBS data acquired at 1.5T to evaluate its efficacy for DBS target localization as compared to using a standard atlas. Results The unbiased templates provide superb detail of subcortical structures. Through one-way ANOVA tests, the unbiased template is significantly (p <0.05) more accurate than a single-template in atlas-based segmentation and DBS target localization tasks. Conclusion The generated unbiased averaged templates provide better visualization of deep brain nuclei and an increase in accuracy over single-template and lower field strength atlases.

Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smart, Oliver S., E-mail: osmart@globalphasing.com; Womack, Thomas O.; Flensburg, Claus

2012-04-01

Local structural similarity restraints (LSSR) provide a novel method for exploiting NCS or structural similarity to an external target structure. Two examples are given where BUSTER re-refinement of PDB entries with LSSR produces marked improvements, enabling further structural features to be modelled. Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct ‘target’ structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less thanmore » 5.5 Å between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and @@target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries http://scripts.iucr.org/cgi-bin/cr.cgi?rm, where -target enables the correct ligand-binding structure to be found, and http://scripts.iucr.org/cgi-bin/cr.cgi?rm, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand.« less

Controlling range expansion in habitat networks by adaptively targeting source populations.

PubMed

Hock, Karlo; Wolff, Nicholas H; Beeden, Roger; Hoey, Jessica; Condie, Scott A; Anthony, Kenneth R N; Possingham, Hugh P; Mumby, Peter J

2016-08-01

Controlling the spread of invasive species, pests, and pathogens is often logistically limited to interventions that target specific locations at specific periods. However, in complex, highly connected systems, such as marine environments connected by ocean currents, populations spread dynamically in both space and time via transient connectivity links. This results in nondeterministic future distributions of species in which local populations emerge dynamically and concurrently over a large area. The challenge, therefore, is to choose intervention locations that will maximize the effectiveness of the control efforts. We propose a novel method to manage dynamic species invasions and outbreaks that identifies the intervention locations most likely to curtail population expansion by selectively targeting local populations most likely to expand their future range. Critically, at any point during the development of the invasion or outbreak, the method identifies the local intervention that maximizes the long-term benefit across the ecosystem by restricting species' potential to spread. In so doing, the method adaptively selects the intervention targets under dynamically changing circumstances. To illustrate the effectiveness of the method we applied it to controlling the spread of crown-of-thorns starfish (Acanthaster sp.) outbreaks across Australia's Great Barrier Reef. Application of our method resulted in an 18-fold relative improvement in management outcomes compared with a random targeting of reefs in putative starfish control scenarios. Although we focused on applying the method to reducing the spread of an unwanted species, it can also be used to facilitate the spread of desirable species through connectivity networks. For example, the method could be used to select those fragments of habitat most likely to rebuild a population if they were sufficiently well protected. © 2016 Society for Conservation Biology.

An open label trial of folate receptor-targeted intraoperative molecular imaging to localize pulmonary squamous cell carcinomas

PubMed Central

Predina, Jarrod D.; Newton, Andrew D.; Xia, Leilei; Corbett, Christopher; Connolly, Courtney; Shin, Michael; Sulyok, Lydia Frezel; Litzky, Leslie; Deshpande, Charuhas; Nie, Shuming; Kularatne, Sumith A.; Low, Philip S.; Singhal, Sunil

2018-01-01

Background Clinical applicability of folate receptor-targeted intraoperative molecular imaging (FR-IMI) has been established for surgically resectable pulmonary adenocarcinoma. A role for FR-IMI in other lung cancer histologies has not been studied. In this study, we evaluate feasibility of FR-IMI in patients undergoing pulmonary resection for squamous cell carcinomas (SCCs). Methods In a human clinical trial (NCT02602119), twelve subjects with pulmonary SCCs underwent FR-IMI with a near-infrared contrast agent that targets the folate receptor-α (FRα), OTL38. Near-infrared signal from tumors and benign lung was quantified to calculate tumor-to-background ratios (TBR). Folate receptor-alpha expression was characterized, and histopathologic correlative analyses were performed to evaluate patterns of OTL38 accumulation. An exploratory analysis was performed to determine patient and histopathologic variables that predict tumor fluorescence. Results 9 of 13 SCCs (in 9 of 12 of subjects) displayed intraoperative fluorescence upon NIR evaluation (median TBR, 3.9). OTL38 accumulated within SCCs in a FRα-dependent manner. FR-IMI was reliable in localizing nodules as small as 1.1 cm, and prevented conversion to thoracotomy for nodule localization in three subjects. Upon evaluation of patient and histopathologic variables, in situ fluorescence was associated with distance from the pleural surface, and was independent of alternative variables including tumor size and metabolic activity. Conclusions This work demonstrates that FR-IMI is potentially feasible in 70% of SCC patients, and that molecular imaging can improve localization during minimally invasive pulmonary resection. These findings complement previous data demonstrating that ∼98% of pulmonary adenocarcinomas are localized during FR-IMI and suggest broad applicability for NSCLC patients undergoing resection. PMID:29568374

Local health and social care responses to implementing the national cold weather plan.

PubMed

Heffernan, C; Jones, L; Ritchie, B; Erens, B; Chalabi, Zaid; Mays, N

2017-09-18

The Cold Weather Plan (CWP) for England was launched by the Department of Health in 2011 to prevent avoidable harm to health by cold weather by enabling individuals to prepare and respond appropriately. This study sought the views of local decision makers involved in the implementation of the CWP in the winter of 2012/13 to establish the effects of the CWP on local planning. It was part of a multi-component independent evaluation of the CWP. Ten LA areas were purposively sampled which varied in level of deprivation and urbanism. Fifty-two semi-structured interviews were held with health and social care managers involved in local planning between November 2012 and May 2013. Thematic analysis revealed that the CWP was considered a useful framework to formalize working arrangements between agencies though local leadership varied across localities. There were difficulties in engaging general practitioners, differences in defining vulnerable individuals and a lack of performance monitoring mechanisms. The CWP was welcomed by local health and social care managers, and improved proactive winter preparedness. Areas for improvement include better integration with general practice, and targeting resources at socially isolated individuals in cold homes with specific interventions aimed at reducing social isolation and building community resilience. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Targeted therapies in the treatment of urothelial cancers.

PubMed

Aragon-Ching, Jeanny B; Trump, Donald L

2017-07-01

Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

Using local authority data for action on health inequalities: the Caerphilly Health and Social Needs Study.

PubMed Central

Fone, David; Jones, Andrew; Watkins, John; Lester, Nathan; Cole, Jane; Thomas, Gary; Webber, Margaret; Coyle, Edward

2002-01-01

BACKGROUND: Primary care organisations in the United Kingdom have been given new and challenging population health responsibilities to improve health and address health inequality in local communities through partnership working with local authorities. This requires robust health and social needs assessment data for effective local planning. AIM: To assess the use and value of local authority data shared through partnership working between Caerphilly Local Health Group and Caerphilly County Borough Council. DESIGN OF STUDY: Cross-sectional analysis of aggregate electoral division data. SETTING: Caephilly County Borough, south-east Wales. METHOD: Local authority datasets identified were categorised into one of six domains: income, unemployment, housing, health, education, and social services. Data were presented at electoral division level as rates in thematic maps and correlations between the variables within and between each domain were explored using Spearman's rank correlation coefficient, with particular focus on children in families. Local planning documents were scrutinised to ascertain the use and value of the data. RESULTS: A broad range of data described a comprehensive picture of health and social inequalities within the borough. Multiple deprivation tended to cluster in electoral divisions, particularly for data relating to children, painting an overwhelming picture of inequality in life chances. The data were used in a wide range of local partnership planning initiatives, including the Health Improvement Programme, Children's Services Plan, and a successful Healthy Living Centre bid. CONCLUSION: Local authority data can help primary care organisations in a population approach to needs assessment for use in local partnership planning targeted at reducing health inequalities. PMID:12392118

Perceptual learning through optimization of attentional weighting: human versus optimal Bayesian learner

NASA Technical Reports Server (NTRS)

Eckstein, Miguel P.; Abbey, Craig K.; Pham, Binh T.; Shimozaki, Steven S.

2004-01-01

Human performance in visual detection, discrimination, identification, and search tasks typically improves with practice. Psychophysical studies suggest that perceptual learning is mediated by an enhancement in the coding of the signal, and physiological studies suggest that it might be related to the plasticity in the weighting or selection of sensory units coding task relevant information (learning through attention optimization). We propose an experimental paradigm (optimal perceptual learning paradigm) to systematically study the dynamics of perceptual learning in humans by allowing comparisons to that of an optimal Bayesian algorithm and a number of suboptimal learning models. We measured improvement in human localization (eight-alternative forced-choice with feedback) performance of a target randomly sampled from four elongated Gaussian targets with different orientations and polarities and kept as a target for a block of four trials. The results suggest that the human perceptual learning can occur within a lapse of four trials (<1 min) but that human learning is slower and incomplete with respect to the optimal algorithm (23.3% reduction in human efficiency from the 1st-to-4th learning trials). The greatest improvement in human performance, occurring from the 1st-to-2nd learning trial, was also present in the optimal observer, and, thus reflects a property inherent to the visual task and not a property particular to the human perceptual learning mechanism. One notable source of human inefficiency is that, unlike the ideal observer, human learning relies more heavily on previous decisions than on the provided feedback, resulting in no human learning on trials following a previous incorrect localization decision. Finally, the proposed theory and paradigm provide a flexible framework for future studies to evaluate the optimality of human learning of other visual cues and/or sensory modalities.

Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713.

PubMed

Leichman, Cynthia Gail; McDonough, Shannon L; Smalley, Stephen R; Billingsley, Kevin G; Lenz, Heinz-Josef; Beldner, Matthew A; Hezel, Aram F; Velasco, Mario R; Guthrie, Katherine A; Blanke, Charles D; Hochster, Howard S

2018-03-01

Neoadjuvant chemoradiation (NCRT) is standard treatment for locally advanced rectal cancer. Pathologic complete response (pCR) has associated with improved survival. In modern phase III trials of NCRT, pCR ranges from 10% to 20%. Cetuximab improves response in KRAS (KRAS proto-oncogene) wild type (wt) metastatic colorectal cancer. S0713 was designed to assess improvement in pCR with additional use of cetuximab with induction chemotherapy and NCRT for locally advanced, KRAS-wt rectal cancer. Patient eligibility: stage II to III biopsy-proven, KRAS-wt rectal adenocarcinoma; no bowel obstruction; adequate hematologic, hepatic and renal function; performance status of 0 to 2. Target enrollment: 80 patients. induction chemotherapy with wCAPOX (weekly capecitabine and oxaliplatin) and cetuximab followed by the same regimen concurrent with radiation (omitting day 15 oxaliplatin). If fewer than 7 pCRs were observed at planned interim analysis after 40 patients received all therapy, the study would close. Eighty eligible patients would provide 90% power given a true pCR rate > 35% at a significance of 0.04. The regimen would lack future interest if pCR probability was ≤ 20%. Between February 2009 and April 2013, 83 patients registered. Four were ineligible and 4 not treated, leaving 75 evaluable for clinical outcomes and toxicity, of whom 65 had surgery. Of 75 patients, 20 had pCR (27%; 95% confidence interval [CI], 17%-38%); 19 (25%) had microscopic cancer; 36 (48%) had minor/no response (including 10 without surgery). Three-year disease-free survival was 73% (95% CI, 63%-83%). Our trial did not meet the pCR target of 35%. Toxicity was generally acceptable. This regimen cannot be recommended outside the clinical trial setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Enabling nutrient security and sustainability through systems research.

PubMed

Kaput, Jim; Kussmann, Martin; Mendoza, Yery; Le Coutre, Ronit; Cooper, Karen; Roulin, Anne

2015-05-01

Human and companion animal health depends upon nutritional quality of foods. Seed varieties, seasonal and local growing conditions, transportation, food processing, and storage, and local food customs can influence the nutrient content of food. A new and intensive area of investigation is emerging that recognizes many factors in these agri-food systems that influence the maintenance of nutrient quality which is fundamental to ensure nutrient security for world populations. Modeling how these systems function requires data from different sectors including agricultural, environmental, social, and economic, but also must incorporate basic nutrition and other biomedical sciences. Improving the agri-food system through advances in pre- and post-harvest processing methods, biofortification, or fortifying processed foods will aid in targeting nutrition for populations and individuals. The challenge to maintain and improve nutrient quality is magnified by the need to produce food locally and globally in a sustainable and consumer-acceptable manner for current and future populations. An unmet requirement for assessing how to improve nutrient quality, however, is the basic knowledge of how to define health. That is, health cannot be maintained or improved by altering nutrient quality without an adequate definition of what health means for individuals and populations. Defining and measuring health therefore becomes a critical objective for basic nutritional and other biomedical sciences.

Minimally invasive treatment for localized prostate cancer.

PubMed

Porres, D; Pfister, D; Heidenreich, A

2012-12-01

The vast majority of men newly diagnosed with prostate cancer have clinically localized disease. Besides active surveillance in low risk cancers and open radical prostatectomy as the traditional gold standard more and more patients demand a effective tumor control through a minimally invasive approach. After the introduction of laparoscopy for the treatment of prostate cancer especially the robot-assisted radical prostatectomy gained in importance. In recent years the accuracy for cancer localisation within the prostate was considerably improved, which enables the increasing use of focal therapy techniques. In addition to the robot-assisted and conventional laparoscopic radical prostatectomy the current and future importance of cryotherapy, HIFU and vascular targeted photodynamic therapy for localized prostate cancer will be analyzed in the following review article.

Localized CT-Guided Irradiation Inhibits Neurogenesis in Specific Regions of the Adult Mouse Brain

PubMed Central

Ford, E. C.; Achanta, P.; Purger, D.; Armour, M.; Reyes, J.; Fong, J.; Kleinberg, L.; Redmond, K.; Wong, J.; Jang, M. H.; Jun, H.; Song, H-J.; Quinones-Hinojosa, A.

2011-01-01

Radiation is used in the study of neurogenesis in the adult mouse both as a model for patients undergoing radiation therapy for CNS malignancies and as a tool to interrupt neurogenesis. We describe the use of a dedicated CT-guided precision device to irradiate specific sub-regions of the adult mouse brain. Improved CT visualization was accomplished with intrathecal injection of iodinated contrast agent, which enhances the lateral ventricles. T2-weighted MRI images were also used for target localization. Visualization of delivered beams (10 Gy) in tissue was accomplished with immunohistochemical staining for the protein γ-H2AX, a marker of DNA double-strand breaks. γ-H2AX stains showed that the lateral ventricle wall could be targeted with an accuracy of 0.19 mm (n = 10). In the hippocampus, γ-H2AX staining showed that the dentate gyrus can be irradiated unilaterally with a localized arc treatment. This resulted in a significant decrease of proliferative neural progenitor cells as measured by Ki-67 staining (P < 0.001) while leaving the contralateral side intact. Two months after localized irradiation, neurogenesis was significantly inhibited in the irradiated region as seen with EdU/NeuN double labeling (P < 0.001). Localized radiation in the rodent brain is a promising new tool for the study of neurogenesis. PMID:21449714

Assessing the performance of quantitative image features on early stage prediction of treatment effectiveness for ovary cancer patients: a preliminary investigation

NASA Astrophysics Data System (ADS)

Zargari, Abolfazl; Du, Yue; Thai, Theresa C.; Gunderson, Camille C.; Moore, Kathleen; Mannel, Robert S.; Liu, Hong; Zheng, Bin; Qiu, Yuchen

2018-02-01

The objective of this study is to investigate the performance of global and local features to better estimate the characteristics of highly heterogeneous metastatic tumours, for accurately predicting the treatment effectiveness of the advanced stage ovarian cancer patients. In order to achieve this , a quantitative image analysis scheme was developed to estimate a total of 103 features from three different groups including shape and density, Wavelet, and Gray Level Difference Method (GLDM) features. Shape and density features are global features, which are directly applied on the entire target image; wavelet and GLDM features are local features, which are applied on the divided blocks of the target image. To assess the performance, the new scheme was applied on a retrospective dataset containing 120 recurrent and high grade ovary cancer patients. The results indicate that the three best performed features are skewness, root-mean-square (rms) and mean of local GLDM texture, indicating the importance of integrating local features. In addition, the averaged predicting performance are comparable among the three different categories. This investigation concluded that the local features contains at least as copious tumour heterogeneity information as the global features, which may be meaningful on improving the predicting performance of the quantitative image markers for the diagnosis and prognosis of ovary cancer patients.

Manage your human sigma.

PubMed

Fleming, John H; Coffman, Curt; Harter, James K

2005-01-01

If sales and service organizations are to improve, they must learn to measure and manage the quality of the employee-customer encounter. Quality improvement methodologies such as Six Sigma are extremely useful in manufacturing contexts, but they're less useful when it comes to human interactions. To address this problem, the authors have developed a quality improvement approach they refer to as Human Sigma. It weaves together a consistent method for assessing the employee-customer encounter and a disciplined process for managing and improving it. There are several core principles for measuring and managing the employee-customer encounter: It's important not to think like an economist or an engineer when assessing interactions because emotions inform both sides' judgments and behavior. The employee-customer encounter must be measured and managed locally, because there are enormous variations in quality at the work-group and individual levels. And to improve the quality of the employee-customer interaction, organizations must conduct both short-term, transactional interventions and long-term, transformational ones. Employee engagement and customer engagement are intimately connected--and, taken together, they have an outsized effect on financial performance. They therefore need to be managed holistically. That is, the responsibility for measuring and monitoring the health of employee-customer relationships must reside within a single organizational structure, with an executive champion who has the authority to initiate and manage change. Nevertheless, the local manager remains the single most important factor in local group performance. A local manager whose work group shows suboptimal performance should be encouraged to conduct interventions, such as targeted training, performance reviews, action learning, and individual coaching.

Synthetic aperture imaging in ultrasound calibration

NASA Astrophysics Data System (ADS)

Ameri, Golafsoun; Baxter, John S. H.; McLeod, A. Jonathan; Jayaranthe, Uditha L.; Chen, Elvis C. S.; Peters, Terry M.

2014-03-01

Ultrasound calibration allows for ultrasound images to be incorporated into a variety of interventional applica­ tions. Traditional Z- bar calibration procedures rely on wired phantoms with an a priori known geometry. The line fiducials produce small, localized echoes which are then segmented from an array of ultrasound images from different tracked probe positions. In conventional B-mode ultrasound, the wires at greater depths appear blurred and are difficult to segment accurately, limiting the accuracy of ultrasound calibration. This paper presents a novel ultrasound calibration procedure that takes advantage of synthetic aperture imaging to reconstruct high resolution ultrasound images at arbitrary depths. In these images, line fiducials are much more readily and accu­ rately segmented, leading to decreased calibration error. The proposed calibration technique is compared to one based on B-mode ultrasound. The fiducial localization error was improved from 0.21mm in conventional B-mode images to 0.15mm in synthetic aperture images corresponding to an improvement of 29%. This resulted in an overall reduction of calibration error from a target registration error of 2.00mm to 1.78mm, an improvement of 11%. Synthetic aperture images display greatly improved segmentation capabilities due to their improved resolution and interpretability resulting in improved calibration.

Toward Intraoperative Image-Guided Transoral Robotic Surgery

PubMed Central

Liu, Wen P.; Reaugamornrat, Sureerat; Deguet, Anton; Sorger, Jonathan M.; Siewerdsen, Jeffrey H.; Richmon, Jeremy; Taylor, Russell H.

2014-01-01

This paper presents the development and evaluation of video augmentation on the stereoscopic da Vinci S system with intraoperative image guidance for base of tongue tumor resection in transoral robotic surgery (TORS). Proposed workflow for image-guided TORS begins by identifying and segmenting critical oropharyngeal structures (e.g., the tumor and adjacent arteries and nerves) from preoperative computed tomography (CT) and/or magnetic resonance (MR) imaging. These preoperative planned data can be deformably registered to the intraoperative endoscopic view using mobile C-arm cone-beam computed tomography (CBCT) [1, 2]. Augmentation of TORS endoscopic video defining surgical targets and critical structures has the potential to improve navigation, spatial orientation, and confidence in tumor resection. Experiments in animal specimens achieved statistically significant improvement in target localization error when comparing the proposed image guidance system to simulated current practice. PMID:25525474

Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives

PubMed Central

2016-01-01

Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response. PMID:27672421

The development of skin immersion clearing method for increasing of laser exposure efficiency on subcutaneous objects

NASA Astrophysics Data System (ADS)

Kozina, Alexandra M.; Genina, Elina A.; Terentyuk, Georgy S.; Terentyuk, Artem G.; Bashkatov, Alexey N.; Tuchin, Valery V.; Khlebtsov, Boris N.

2012-06-01

In this paper we have studied effect of a hyperosmotic optical clearing agent (OCA), such as polyethylene glycol, on the fluorescence intensity from a target located in subcutaneous area in the model experiments. As a fluorescence agent the nanocomposite including gold nanorods with hematophorphyrin was used. The remitted fluorescent signal traveling to the tissue surface was monitored over time as the tissue was treated with the OCA. The detected fluorescent signal increased as the scattering in tissue samples was substantially reduced. The study has shown how OCA can be used to improve the detected signal at localization of subcutaneous target tissue at the photothermal or photodynamic therapy. Immersion clearing of skin can be also useful for improvement of laser exposure efficiency due to the increasing of light penetration depth.

Should the Centers for Disease Control and Prevention’s Childhood Lead Poisoning Intervention Level Be Lowered?

PubMed Central

Bernard, Susan M.

2003-01-01

The US Centers for Disease Control and Prevention (CDC) in 1991 chose 10 μg/dL as an initial screening level for lead in children’s blood. Current data on health risks and intervention options do not support generally lowering that level, but federal lead poisoning prevention efforts can be improved by revising the follow-up testing schedule for infants aged 1 year or less with blood lead levels of 5 μg/dL or higher; universal education about lead exposure risks; universal administration of improved, locally validated risk-screening questionnaires; enhanced compliance with targeted screening recommendations and federal health program requirements; and development by regulatory agencies of primary prevention criteria that do not use the CDC’s intervention level as a target “safe” lead exposure. PMID:12893607

SU-F-BRB-13: Correlation of Improved Target and Organ-At-Risk Dosimetric Quantities and Clinical Outcomes for Helical Tomotherapy Treated Mesothelioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, S; Kishan, A; Alexander, S

2015-06-15

Purpose: We have observed improved local control probability (LCP) for adjuvant mesothelioma radiotherapy following pleurectomy/decortication using Tomotherapy compared to the conventional 3D technique (p<0.05). This work assesses the correlation between the improved clinical outcomes against dosimetry quantities. Methods: Thirty-eight mesothelioma cases consecutively treated at our clinic were retrospectively analyzed. Sixteen patients were treated using 3D technique planned on the Eclipse for c-arm accelerators prior to 7/2012; the other 22 cases were treated on Tomotherapy using helical IMRT after 7/2012. Typical 3D plans consisting of 15 MV AP/PA photon fields prescribed to 10 cm depth followed by matching electron fields withmore » energy ranging from 8–16 MeV. Tomotherapy plans were designed using 2.5cm jaw, 0.287 pitch with directional blocking of the contralateral lung. The same prescription of 45 Gy (1.8GyX25) was used for both techniques. The dosimetry metrics for the critical structures: ipsilateral-/contralateral-lung, heart, cord, esophagus, etc were compared between two techniques. Results: Superior LCP is closely associated with improved target coverage. Tomotherapy plans yielded dramatically better target coverage and less dose heterogeneity despite of more advanced/larger disease. The averaged PTV volumes were 2287.3±569.9 (Tomotherapy) vs. 1904.8±312.3cc (3D); V100s were: 91.1±4.0 (%) vs. 47.8±12.7 (%) with heterogeneity indices of 1.20±0.1 vs.1.37±0.38 and for the Tomotherapy and 3D plans, respectively. Compared to the 3D technique, we observed significant lower maximum cord doses (p<0.001), lower mean esophagus doses (p<0.002), and lower heart mean doses when tumor was left-sided (p=0.002). For ipsilateral-/contralateral-lungs, however, the mean doses and V20, V5 of Tomotherapy plans were significantly higher than the 3D plans (p<0.01) regardless which sides of lung were treated. However, rates of radiation pneumonitis were no different. Conclusion: Tomotherapy achieved great improvement of plan quality including target coverage, resulting in significantly better local control over the traditional 3D technique for adjuvant radiotherapy for mesothelioma.« less

Cancer active targeting by nanoparticles: a comprehensive review of literature

PubMed Central

Bazak, Remon; Houri, Mohamad; Achy, Samar El; Kamel, Serag

2016-01-01

Purpose Cancer is one of the leading causes of death, and thus, the scientific community has but great efforts to improve cancer management. Among the major challenges in cancer management is development of agents that can be used for early diagnosis and effective therapy. Conventional cancer management frequently lacks accurate tools for detection of early tumors and has an associated risk of serious side effects of chemotherapeutics. The need to optimize therapeutic ratio as the difference with which a treatment affects cancer cells versus healthy tissues lead to idea that it is needful to have a treatment that could act a the “magic bullet”—recognize cancer cells only. Nanoparticle platforms offer a variety of potentially efficient solutions for development of targeted agents that can be exploited for cancer diagnosis and treatment. There are two ways by which targeting of nanoparticles can be achieved, namely passive and active targeting. Passive targeting allows for the efficient localization of nanoparticles within the tumor microenvironment. Active targeting facilitates the active uptake of nanoparticles by the tumor cells themselves. Methods Relevant English electronic databases and scientifically published original articles and reviews were systematically searched for the purpose of this review. Results In this report, we present a comprehensive review of literatures focusing on the active targeting of nanoparticles to cancer cells, including antibody and antibody fragment-based targeting, antigen-based targeting, aptamer-based targeting, as well as ligand-based targeting. Conclusion To date, the optimum targeting strategy has not yet been announced, each has its own advantages and disadvantages even though a number of them have found their way for clinical application. Perhaps, a combination of strategies can be employed to improve the precision of drug delivery, paving the way for a more effective personalized therapy. PMID:25005786

Multispectral photoacoustic decomposition with localized regularization for detecting targeted contrast agent

NASA Astrophysics Data System (ADS)

Tavakoli, Behnoosh; Chen, Ying; Guo, Xiaoyu; Kang, Hyun Jae; Pomper, Martin; Boctor, Emad M.

2015-03-01

Targeted contrast agents can improve the sensitivity of imaging systems for cancer detection and monitoring the treatment. In order to accurately detect contrast agent concentration from photoacoustic images, we developed a decomposition algorithm to separate photoacoustic absorption spectrum into components from individual absorbers. In this study, we evaluated novel prostate-specific membrane antigen (PSMA) targeted agents for imaging prostate cancer. Three agents were synthesized through conjugating PSMA-targeting urea with optical dyes ICG, IRDye800CW and ATTO740 respectively. In our preliminary PA study, dyes were injected in a thin wall plastic tube embedded in water tank. The tube was illuminated with pulsed laser light using a tunable Q-switch ND-YAG laser. PA signal along with the B-mode ultrasound images were detected with a diagnostic ultrasound probe in orthogonal mode. PA spectrums of each dye at 0.5 to 20 μM concentrations were estimated using the maximum PA signal extracted from images which are obtained at illumination wavelengths of 700nm-850nm. Subsequently, we developed nonnegative linear least square optimization method along with localized regularization to solve the spectral unmixing. The algorithm was tested by imaging mixture of those dyes. The concentration of each dye was estimated with about 20% error on average from almost all mixtures albeit the small separation between dyes spectrums.

Laser-induced disruption of systemically administered liposomes for targeted drug delivery

NASA Astrophysics Data System (ADS)

Mackanos, Mark A.; Larabi, Malika; Shinde, Rajesh; Simanovskii, Dmitrii M.; Guccione, Samira; Contag, Christopher H.

2009-07-01

Liposomal formulations of drugs have been shown to enhance drug efficacy by prolonging circulation time, increasing local concentration and reducing off-target effects. Controlled release from these formulations would increase their utility, and hyperthermia has been explored as a stimulus for targeted delivery of encapsulated drugs. Use of lasers as a thermal source could provide improved control over the release of the drug from the liposomes with minimal collateral tissue damage. Appropriate methods for assessing local release after systemic delivery would aid in testing and development of better formulations. We use in vivo bioluminescence imaging to investigate the spatiotemporal distribution of luciferin, used as a model small molecule, and demonstrate laser-induced release from liposomes in animal models after systemic delivery. These liposomes were tested for luciferin release between 37 and 45 °C in PBS and serum using bioluminescence measurements. In vivo studies were performed on transgenic reporter mice that express luciferase constitutively throughout the body, thus providing a noninvasive readout for controlled release following systemic delivery. An Nd:YLF laser was used (527 nm) to heat tissues and induce rupture of the intravenously delivered liposomes in target tissues. These data demonstrate laser-mediated control of small molecule delivery using thermally sensitive liposomal formulations.

Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells

PubMed Central

Samse, Kaitlen; Emathinger, Jacqueline; Hariharan, Nirmala; Quijada, Pearl; Ilves, Kelli; Völkers, Mirko; Ormachea, Lucia; De La Torre, Andrea; Orogo, Amabel M.; Alvarez, Roberto; Din, Shabana; Mohsin, Sadia; Monsanto, Megan; Fischer, Kimberlee M.; Dembitsky, Walter P.; Gustafsson, Åsa B.; Sussman, Mark A.

2015-01-01

Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics. PMID:25882843

Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells.

PubMed

Samse, Kaitlen; Emathinger, Jacqueline; Hariharan, Nirmala; Quijada, Pearl; Ilves, Kelli; Völkers, Mirko; Ormachea, Lucia; De La Torre, Andrea; Orogo, Amabel M; Alvarez, Roberto; Din, Shabana; Mohsin, Sadia; Monsanto, Megan; Fischer, Kimberlee M; Dembitsky, Walter P; Gustafsson, Åsa B; Sussman, Mark A

2015-05-29

Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

PubMed

Wilkowski, Ralf; Thoma, Martin; Weingandt, Helmut; Dühmke, Eckhart; Heinemann, Volker

2005-05-10

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

Gold Nanoconstructs for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

NASA Astrophysics Data System (ADS)

Coughlin, Andrew James

Cancer accounts for nearly 1 out of every 4 deaths in the United States, and because conventional treatments are limited by morbidity and off-target toxicities, improvements in cancer management are needed. This thesis further develops nanoparticle-assisted photothermal therapy (NAPT) as a viable treatment option for cancer patients. NAPT enables localized ablation of disease because heat generation only occurs where tissue permissive near-infrared (NIR) light and absorbing nanoparticles are combined, leaving surrounding normal tissue unharmed. Two principle approaches were investigated to improve the specificity of this technique: multimodal imaging and molecular targeting. Multimodal imaging affords the ability to guide NIR laser application for site-specific NAPT and more holistic characterization of disease by combining the advantages of several diagnostic technologies. Towards the goal of image-guided NAPT, gadolinium-conjugated gold-silica nanoshells were engineered and demonstrated to enhance imaging contrast across a range of diagnostic modes, including T1-weighted magnetic resonance imaging, X-Ray, optical coherence tomography, reflective confocal microscopy, and two-photon luminescence in vitro as well as within an animal tumor model. Additionally, the nanoparticle conjugates were shown to effectively convert NIR light to heat for applications in photothermal therapy. Therefore, the broad utility of gadolinium-nanoshells for anatomic localization of tissue lesions, molecular characterization of malignancy, and mediators of ablation was established. Molecular targeting strategies may also improve NAPT by promoting nanoparticle uptake and retention within tumors and enhancing specificity when malignant and normal tissue interdigitate. Here, ephrinA1 protein ligands were conjugated to nanoshell surfaces for particle homing to overexpressed EphA2 receptors on prostate cancer cells. In vitro, successful targeting and subsequent photothermal ablation of prostate cancer cells was achieved with negligible nanoshell binding to normal cells. In vivo however, ephrinA1-nanoshells did not promote enhanced therapeutic outcomes in mice bearing subcutaneous prostate cancer tumors treated with NAPT compared to nontargeted particles. Nonetheless, both treatment groups demonstrated effective ablation of prostate tumors, as evidenced by tumor tissue regression. Further investigation is warranted to overcome probable protein immunogenicity that offsets ephrinA1 targeting in vivo. With future study, photothermal therapy with multimodal gadolinium-conjugated and molecularly targeted nanoshells may offer a viable treatment option for cancer patients in the clinic.

Local search to improve coordinate-based task mapping

DOE PAGES

Balzuweit, Evan; Bunde, David P.; Leung, Vitus J.; ...

2015-10-31

We present a local search strategy to improve the coordinate-based mapping of a parallel job’s tasks to the MPI ranks of its parallel allocation in order to reduce network congestion and the job’s communication time. The goal is to reduce the number of network hops between communicating pairs of ranks. Our target is applications with a nearest-neighbor stencil communication pattern running on mesh systems with non-contiguous processor allocation, such as Cray XE and XK Systems. Utilizing the miniGhost mini-app, which models the shock physics application CTH, we demonstrate that our strategy reduces application running time while also reducing the runtimemore » variability. Furthermore, we further show that mapping quality can vary based on the selected allocation algorithm, even between allocation algorithms of similar apparent quality.« less

The effect of a VR exercise program on falls and depression in the elderly with mild depression in the local community.

PubMed

Yang, Jong-Eun; Lee, Tac-Young; Kim, Jin-Kyung

2017-12-01

[Purpose] The purpose of this study is to explore the effect of a VR exercise program on falls and depression in the elderly with mild depression who reside in the local community. [Subjects and Methods] This study was performed by targeting 15 elderly subjects with mild depression who resided in the local community. The targeted subjects voluntarily selected 3 VR exercise programs (each lasting 10 minutes) among 4 activities, and a resting time of 5 minutes was given for an interval after each activity. The VR exercise program was performed for total 12 weeks (36 times), 3 times a week, 45 minutes per session. [Results] After exercise, scores of static balance test (anteroposterior), Falls Efficacy Scale, and the Activities-specific Balance Confidence Scale in the test subjects were improved and depression and internal stress scores were significantly decreased after the intervention. [Conclusion] It can be concluded that the VR exercise program exerts a positive effect not only on the physical factor but also on the mental factor of the elderly subjects with mild depression who reside in the local community. It is expected that based on the VR exercise program, diversified home programs for the elderly should be developed in the future.

Management of Local Stressors Can Improve the Resilience of Marine Canopy Algae to Global Stressors

PubMed Central

Strain, Elisabeth M. A.; van Belzen, Jim; van Dalen, Jeroen; Bouma, Tjeerd J.; Airoldi, Laura

2015-01-01

Coastal systems are increasingly threatened by multiple local anthropogenic and global climatic stressors. With the difficulties in remediating global stressors, management requires alternative approaches that focus on local scales. We used manipulative experiments to test whether reducing local stressors (sediment load and nutrient concentrations) can improve the resilience of foundation species (canopy algae along temperate rocky coastlines) to future projected global climate stressors (high wave exposure, increasing sea surface temperature), which are less amenable to management actions. We focused on Fucoids (Cystoseira barbata) along the north-western Adriatic coast in the Mediterranean Sea because of their ecological relevance, sensitivity to a variety of human impacts, and declared conservation priority. At current levels of sediment and nutrients, C. barbata showed negative responses to the simulated future scenarios of high wave exposure and increased sea surface temperature. However, reducing the sediment load increased the survival of C. barbata recruits by 90.24% at high wave exposure while reducing nutrient concentrations resulted in a 20.14% increase in the survival and enhanced the growth of recruited juveniles at high temperature. We conclude that improving water quality by reducing nutrient concentrations, and particularly the sediment load, would significantly increase the resilience of C. barbata populations to projected increases in climate stressors. Developing and applying appropriate targets for specific local anthropogenic stressors could be an effective management action to halt the severe and ongoing loss of key marine habitats. PMID:25807516

A Reverse Localization Scheme for Underwater Acoustic Sensor Networks

PubMed Central

Moradi, Marjan; Rezazadeh, Javad; Ismail, Abdul Samad

2012-01-01

Underwater Wireless Sensor Networks (UWSNs) provide new opportunities to observe and predict the behavior of aquatic environments. In some applications like target tracking or disaster prevention, sensed data is meaningless without location information. In this paper, we propose a novel 3D centralized, localization scheme for mobile underwater wireless sensor network, named Reverse Localization Scheme or RLS in short. RLS is an event-driven localization method triggered by detector sensors for launching localization process. RLS is suitable for surveillance applications that require very fast reactions to events and could report the location of the occurrence. In this method, mobile sensor nodes report the event toward the surface anchors as soon as they detect it. They do not require waiting to receive location information from anchors. Simulation results confirm that the proposed scheme improves the energy efficiency and reduces significantly localization response time with a proper level of accuracy in terms of mobility model of water currents. Major contributions of this method lie on reducing the numbers of message exchange for localization, saving the energy and decreasing the average localization response time. PMID:22666034

A reverse localization scheme for underwater acoustic sensor networks.

PubMed

Moradi, Marjan; Rezazadeh, Javad; Ismail, Abdul Samad

2012-01-01

Underwater Wireless Sensor Networks (UWSNs) provide new opportunities to observe and predict the behavior of aquatic environments. In some applications like target tracking or disaster prevention, sensed data is meaningless without location information. In this paper, we propose a novel 3D centralized, localization scheme for mobile underwater wireless sensor network, named Reverse Localization Scheme or RLS in short. RLS is an event-driven localization method triggered by detector sensors for launching localization process. RLS is suitable for surveillance applications that require very fast reactions to events and could report the location of the occurrence. In this method, mobile sensor nodes report the event toward the surface anchors as soon as they detect it. They do not require waiting to receive location information from anchors. Simulation results confirm that the proposed scheme improves the energy efficiency and reduces significantly localization response time with a proper level of accuracy in terms of mobility model of water currents. Major contributions of this method lie on reducing the numbers of message exchange for localization, saving the energy and decreasing the average localization response time.

Developing effective policy and practice for health promotion in Scotland.

PubMed

Wimbush, Erica; Young, Ian; Robertson, Graham

2007-01-01

Scotland has recently embarked on a new phase of policy and infrastructure development for improving population health and reducing health inequalities that broadly conforms to the Ottawa Charter and WHO's strategic framework for the prevention and control of non-communicable diseases. The new phase is characterised by an integrated, cross-government approach to improving health with strengthened political and Scottish Executive leadership and investment since devolution. A comprehensive policy framework for improving young people's health and reducing inequalities has been developed across education, health, environment and social justice. It builds on an earlier phase of relative stability and continuity in the health promotion infrastructure with policy focused on CVD and cancer prevention and tackling the behavioural risk factors (smoking, alcohol, diet, physical activity) as well as sexual health and mental health and wellbeing. These national strategies are currently being implemented across Scotland. They combine promotion, prevention, treatment and protection goals and target both population-level and high-risk groups. Crosscutting government objectives and headline targets for addressing poverty, disadvantage and health inequalities now supplement the NHS health improvement targets on smoking, alcohol, physical activity, teenage pregnancy and child immunization. Within the health service, prevention efforts are largely concerned with primary care development (anticipatory care) and health system reform to maximize their impact on reducing health inequalities. Efforts to tackle the social determinants of health and reduce inequalities in health outcomes are beginning to be connected and mainstreamed across local government with Community Planning Partnerships as the main vehicle. National level mechanisms for integrated funding, planning and performance reporting to deliver shared priority outcomes have yet to be developed. The development of health improvement strategies has been founded upon a rich source of population health data to monitor changes and improvements, epidemiological studies and evaluation work. The key issues have been to find ways of intervening to accelerate the rate of improvement and to stem the growing health inequalities. A further challenge is to ensure that the lessons from reviews and evaluations of past programmes and strategies are not lost, but help to guide improvements in the complex delivery system and to inform future policy direction. Within the health service, prevention efforts are largely concerned with primary care development and health system reform. Efforts to reduce inequalities in health outcomes are beginning to be connected and mainstreamed across local government.

Local Setup Reproducibility of the Spinal Column When Using Intensity-Modulated Radiation Therapy for Craniospinal Irradiation With Patient in Supine Position

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoiber, Eva Maria, E-mail: eva.stoiber@med.uni-heidelberg.de; Department of Medical Physics, German Cancer Research Center, Heidelberg; Giske, Kristina

Purpose: To evaluate local positioning errors of the lumbar spine during fractionated intensity-modulated radiotherapy of patients treated with craniospinal irradiation and to assess the impact of rotational error correction on these uncertainties for one patient setup correction strategy. Methods and Materials: 8 patients (6 adults, 2 children) treated with helical tomotherapy for craniospinal irradiation were retrospectively chosen for this analysis. Patients were immobilized with a deep-drawn Aquaplast head mask. Additionally to daily megavoltage control computed tomography scans of the skull, once-a-week positioning of the lumbar spine was assessed. Therefore, patient setup was corrected by a target point correction, derived frommore » a registration of the patient's skull. The residual positioning variations of the lumbar spine were evaluated applying a rigid-registration algorithm. The impact of different rotational error corrections was simulated. Results: After target point correction, residual local positioning errors of the lumbar spine varied considerably. Craniocaudal axis rotational error correction did not improve or deteriorate these translational errors, whereas simulation of a rotational error correction of the right-left and anterior-posterior axis increased these errors by a factor of 2 to 3. Conclusion: The patient fixation used allows for deformations between the patient's skull and spine. Therefore, for the setup correction strategy evaluated in this study, generous margins for the lumbar spinal target volume are needed to prevent a local geographic miss. With any applied correction strategy, it needs to be evaluated whether or not a rotational error correction is beneficial.« less

Antibody therapeutics for treating prostate cancer: where are we now and what comes next?

PubMed

Vlachostergios, Panagiotis J; Galletti, Giuseppe; Palmer, Jessica; Lam, Linda; Karir, Beerinder S; Tagawa, Scott T

2017-02-01

Progress in the understanding of molecular events of carcinogenesis and cancer evolution as well as the identification of tumor antigens has led to the development of different targeted therapeutic approaches, including the use of monoclonal antibodies (mAbs). Prostate cancer (PC) is highly amenable to mAb targeting given the existence of prostate-specific targets and the natural history and localization of metastatic disease. Areas covered: Several aspects of the PC phenotype, including growth factors, angiogenesis mediators, bone microenvironment signals, and immune evasion pathways, have become areas of ongoing investigation in terms of mAb targeting. These are reviewed. The greatest success so far has been the development of mAbs against prostate-specific tumor antigen (PSMA), which opened an opportunity to improve diagnostic accuracy and simultaneously target metastatic disease. Expert opinion: As mAb use in PC continues to evolve, more accurate imaging of the extent of disease and more effective mAb therapies (naked or conjugated with drugs, toxins or radioactive molecules) are emerging. In addition, the combination of mAbs with other treatment modalities is expected to further improve responses and overall survival. Identification of validated biomarkers is necessary for better recognition of patient subgroups who will derive the greatest benefit from mAb therapy.

Targeted Delivery of Toxoplasma gondii Antigens to Dendritic Cells Promote Immunogenicity and Protective Efficiency against Toxoplasmosis

PubMed Central

Lakhrif, Zineb; Moreau, Alexis; Hérault, Bruno; Di-Tommaso, Anne; Juste, Matthieu; Moiré, Nathalie; Dimier-Poisson, Isabelle; Mévélec, Marie-Noëlle; Aubrey, Nicolas

2018-01-01

Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination against Toxoplasma gondii requires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity to T. gondii. In this study, we explore an original vaccination strategy that combines administration via mucosal and systemic routes of fusion proteins able to target the major T. gondii surface antigen SAG1 to DCs using an antibody fragment single-chain fragment variable (scFv) directed against DEC205 endocytic receptor. Our results show that SAG1 targeting to DCs by scFv via intranasal and subcutaneous administration improved protection against chronic T. gondii infection. A marked reduction in brain parasite burden is observed when compared with the intranasal or the subcutaneous route alone. DC targeting improved both local and systemic humoral and cellular immune responses and potentiated more specifically the Th1 response profile by more efficient production of IFN-γ, interleukin-2, IgG2a, and nasal IgA. This study provides evidence of the potential of DC targeting for the development of new vaccines against a range of Apicomplexa parasites. PMID:29515595

Dosimetric comparison between conventional and conformal radiotherapy for carcinoma cervix: Are we treating the right volumes?

PubMed Central

Goswami, Jyotirup; Patra, Niladri B.; Sarkar, Biplab; Basu, Ayan; Pal, Santanu

2013-01-01

Background and Purpose: Conventional portals, based on bony anatomy, for external beam radiotherapy for cervical cancer have been repeatedly demonstrated as inadequate. Conversely, with image-based conformal radiotherapy, better target coverage may be offset by the greater toxicities and poorer compliance associated with treating larger volumes. This study was meant to dosimetrically compare conformal and conventional radiotherapy. Materials and Methods: Five patients of carcinoma cervix underwent planning CT scan with IV contrast and targets, and organs at risk (OAR) were contoured. Two sets of plans-conventional and conformal were generated for each patient. Field sizes were recorded, and dose volume histograms of both sets of plans were generated and compared on the basis of target coverage and OAR sparing. Results: Target coverage was significantly improved with conformal plans though field sizes required were significantly larger. On the other hand, dose homogeneity was not significantly improved. Doses to the OARs (rectum, urinary bladder, and small bowel) were not significantly different across the 2 arms. Conclusion: Three-dimensional conformal radiotherapy gives significantly better target coverage, which may translate into better local control and survival. On the other hand, it also requires significantly larger field sizes though doses to the OARs are not significantly increased. PMID:24455584

The Role of School Development in the School Improvement Process of Prince George's County. Lessons Learned from One Local District's Perspective.

ERIC Educational Resources Information Center

Grady, Michael K.

In September 1985, the Prince George's County Public School System located in the Washington metropolitan area east of the District of Columbia, began implementation of a Milliken relief program to revamp its equity strategy. Initially, 10 of 117 elementary schools in the system were targeted for relief, but by September 1988, the Milliken program…

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight

PubMed Central

Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

2017-01-01

Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels. PMID:28817602

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

PubMed

Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

2017-01-01

Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy.

PubMed

Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Høgset, Anders; Selbo, Pål Kristian

2015-05-28

The cancer stem cell (CSC) marker CD133 is an attractive target to improve antitumor therapy. We have used photochemical internalization (PCI) for the endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133-saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which generates reactive oxygen species upon light-activation causing a rupture of the vesicle membranes and endosomal escape of entrapped drugs. Here we show that AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation and induced 100% inhibition of cell viability and colony forming ability at the highest light doses, whereas no cytotoxicity was obtained in the absence of light. Efficient PCI-based CD133-targeting was in addition demonstrated in the stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin induced mainly necrosis and a minimal apoptotic response based on assessing cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in S phase arrest and reduced LC3-II conversion compared to control treatments. Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II conversion, indicating a termination of the autophagic flux in WiDr cells. For the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor response was observed after PCIAC133-saporin. The present PCI-based endosomal escape technology represents a minimally invasive strategy for spatio-temporal, light-controlled targeting of CD133+ cells in localized primary tumors or metastasis. Copyright © 2015 Elsevier B.V. All rights reserved.

Alternating magnetic field optimization for IONP hyperthermia cancer treatment

NASA Astrophysics Data System (ADS)

Kastner, Elliot J.; Reeves, Russell; Bennett, William; Misra, Aditi; Petryk, Jim D.; Petryk, Alicia A.; Hoopes, P. Jack

2015-03-01

Iron oxide nanoparticles (IONP) have therapeutic potential to deliver a thermal dose to tumors when activated in an alternating magnetic field (AMF). Through various targeting methods such as antibody labeling or injection site choice, delivery of IONPs to tumors yields enhanced treatment accuracy and efficacy. Despite this advantage, delivery an AMF, which is sufficient to result in clinically relevant IONP heating, can result in nonspecific tissue heating via the generation of eddy currents and tissue permeated by local electric fields (joule heating). The production of eddy current heating is a function of tissue size, geometry and composition as well as coil design and operation. The purpose of this research is to increase the level of energy deposited into the IONPs versus the non-target tissue (power ratio/PR)1 in order to improve target heating and reduce nonspecific tissue damage. We propose to improve the PR using two primary concepts: (1) reduce power deposition into non-target tissue by manipulating the fields and eddy current flow and (2) enhance heat removal from non-target tissue. We have shown that controlling tissue placement within the AMF field, accounting for tissue geometry, utilizing external cooling devices, and modifying the field properties can decrease non-target heating by more than 50%, at clinically relevant AMF levels, thereby allowing for an increase in thermal dose to the tumor and increasing the therapeutic ratio.

Physical property control in core/shell inorganic nanostructures for fluorescence and magnetic targeting applications

NASA Astrophysics Data System (ADS)

Roberts, Stephen K.

Nanomaterials show immense promise for the future in numerous areas of application. Properties that are unique from the bulk material and are tunable allow for innovation in material design. This thesis will focus on controlling the physical properties of core/shell nanostructures to enhance the utility of the materials. The first focus is on the impact of different solvent mixtures during the shell growth phase of SILAR based core/shell quantum dot synthesis is studied. Gaining insight into the mechanism for SILAR growth of core/shell nanoparticles allows improved synthetic yields and precursor binding, providing enhanced control to synthesis of core/shell nanoparticles. The second focus of this thesis is exploring the use of magnetic nanoparticles for magnetic drug targeting for cardiovascular conditions. Magnetic targeting for drug delivery enables increased local drug concentration, while minimizing non-specific interactions. In order to be effective for magnetic targeting, it must be shown that low magnetic strength is sufficient to capture flowing nanoparticles. By demonstrating the binding of a therapeutic agent to the surface at medicinal levels, the viability for use as a nanoparticle drug delivery system is improved.

Sounds activate visual cortex and improve visual discrimination.

PubMed

Feng, Wenfeng; Störmer, Viola S; Martinez, Antigona; McDonald, John J; Hillyard, Steven A

2014-07-16

A recent study in humans (McDonald et al., 2013) found that peripheral, task-irrelevant sounds activated contralateral visual cortex automatically as revealed by an auditory-evoked contralateral occipital positivity (ACOP) recorded from the scalp. The present study investigated the functional significance of this cross-modal activation of visual cortex, in particular whether the sound-evoked ACOP is predictive of improved perceptual processing of a subsequent visual target. A trial-by-trial analysis showed that the ACOP amplitude was markedly larger preceding correct than incorrect pattern discriminations of visual targets that were colocalized with the preceding sound. Dipole modeling of the scalp topography of the ACOP localized its neural generators to the ventrolateral extrastriate visual cortex. These results provide direct evidence that the cross-modal activation of contralateral visual cortex by a spatially nonpredictive but salient sound facilitates the discriminative processing of a subsequent visual target event at the location of the sound. Recordings of event-related potentials to the targets support the hypothesis that the ACOP is a neural consequence of the automatic orienting of visual attention to the location of the sound. Copyright © 2014 the authors 0270-6474/14/349817-08$15.00/0.

Automated protein structure modeling in CASP9 by I-TASSER pipeline combined with QUARK-based ab initio folding and FG-MD-based structure refinement

PubMed Central

Xu, Dong; Zhang, Jian; Roy, Ambrish; Zhang, Yang

2011-01-01

I-TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and FG-MD, were added to the I-TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I-TASSER structure assembly simulations. FG-MD is an atomic-level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen-bonding networks, torsion angles and steric clashes. Despite considerable progress in both the template-based and template-free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of beta-proteins are still needed to further improve the I-TASSER pipeline. PMID:22069036

Performing a local barrier operation

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2014-03-04

Performing a local barrier operation with parallel tasks executing on a compute node including, for each task: retrieving a present value of a counter; calculating, in dependence upon the present value of the counter and a total number of tasks performing the local barrier operation, a base value, the base value representing the counter's value prior to any task joining the local barrier; calculating, in dependence upon the base value and the total number of tasks performing the local barrier operation, a target value of the counter, the target value representing the counter's value when all tasks have joined the local barrier; joining the local barrier, including atomically incrementing the value of the counter; and repetitively, until the present value of the counter is no less than the target value of the counter: retrieving the present value of the counter and determining whether the present value equals the target value.

Performing a local barrier operation

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2014-03-04

Performing a local barrier operation with parallel tasks executing on a compute node including, for each task: retrieving a present value of a counter; calculating, in dependence upon the present value of the counter and a total number of tasks performing the local barrier operation, a base value of the counter, the base value representing the counter's value prior to any task joining the local barrier; calculating, in dependence upon the base value and the total number of tasks performing the local barrier operation, a target value, the target value representing the counter's value when all tasks have joined the local barrier; joining the local barrier, including atomically incrementing the value of the counter; and repetitively, until the present value of the counter is no less than the target value of the counter: retrieving the present value of the counter and determining whether the present value equals the target value.

Status of the Local Enforcement of Energy Efficiency Standards and Labeling Program in China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Nan; Zheng, Nina; Fino-Chen, Cecilia

2011-09-26

As part of its commitment to promoting and improving the local enforcement of appliance energy efficiency standards and labeling, the China National Institute of Standardization (CNIS) launched the National and Local Enforcement of Energy Efficiency Standards and Labeling project on August 14, 2009. The project’s short-term goal is to expand the effort to improve enforcement of standards and labeling requirements to the entire country within three years, with a long-term goal of perfecting overall enforcement. For this project, Jiangsu, Shandong, Sichuan and Shanghai were selected as pilot locations. This report provides information on the local enforcement project’s recent background, activitiesmore » and results as well as comparison to previous rounds of check-testing in 2006 and 2007. In addition, the report also offers evaluation on the achievement and weaknesses in the local enforcement scheme and recommendations. The results demonstrate both improvement and some backsliding. Enforcement schemes are in place in all target cities and applicable national standards and regulations were followed as the basis for local check testing. Check testing results show in general high labeling compliance across regions with 100% compliance for five products, including full compliance for all three products tested in Jiangsu province and two out of three products tested in Shandong province. Program results also identified key weaknesses in labeling compliance in Sichuan as well as in the efficiency standards compliance levels for small and medium three-phase asynchronous motors and self-ballasted fluorescent lamps. For example, compliance for the same product ranged from as low as 40% to 100% with mixed results for products that had been tested in previous rounds. For refrigerators, in particular, the efficiency standards compliance rate exhibited a wider range of 50% to 100%, and the average rate across all tested models also dropped from 96% in 2007 to 63%, possibly due to the implementation of newly strengthened efficiency standards in 2009. Areas for improvement include: Greater awareness at the local level to ensure that all manufacturers register their products with the label certification project and to minimize their resistance to inspections; improvement of the product sampling methodology to include representative testing of both large and small manufacturers and greater standardization of testing tools and procedures; and continued improvement in local enforcement efforts.« less

From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer.

PubMed

Leonardi, Maria Cristina; Ricotti, Rosalinda; Dicuonzo, Samantha; Cattani, Federica; Morra, Anna; Dell'Acqua, Veronica; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

2016-10-01

Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue. The widespread use of dose-volume constraints and histograms have increased awareness of toxicity. Real time image guidance has improved geometric precision and accuracy, together with the implementation of quality assurance programs. Advances in the precision of radiotherapy is also based on the choice of the appropriate fractionation and approach. Adaptive radiotherapy is not only a technical concept, but is also a biological concept based on the knowledge that different types of BC have distinctive patterns of locoregional spread. A greater understanding of cancer biology helps in choosing the treatment best suited to a particular situation. Biomarkers predictive of response play a crucial role. The combination of radiotherapy with molecular targeted therapies may enhance radiosensitivity, thus increasing the cytotoxic effects and improving treatment response. The appropriateness of an alternative fractionation, partial breast irradiation, dose escalating/de-escalating approaches, the extent of nodal irradiation have been examined for all the BC subtypes. The broadened concept of adaptive radiotherapy is vital to high-precision treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ligand Binding Site Detection by Local Structure Alignment and Its Performance Complementarity

PubMed Central

Lee, Hui Sun; Im, Wonpil

2013-01-01

Accurate determination of potential ligand binding sites (BS) is a key step for protein function characterization and structure-based drug design. Despite promising results of template-based BS prediction methods using global structure alignment (GSA), there is a room to improve the performance by properly incorporating local structure alignment (LSA) because BS are local structures and often similar for proteins with dissimilar global folds. We present a template-based ligand BS prediction method using G-LoSA, our LSA tool. A large benchmark set validation shows that G-LoSA predicts drug-like ligands’ positions in single-chain protein targets more precisely than TM-align, a GSA-based method, while the overall success rate of TM-align is better. G-LoSA is particularly efficient for accurate detection of local structures conserved across proteins with diverse global topologies. Recognizing the performance complementarity of G-LoSA to TM-align and a non-template geometry-based method, fpocket, a robust consensus scoring method, CMCS-BSP (Complementary Methods and Consensus Scoring for ligand Binding Site Prediction), is developed and shows improvement on prediction accuracy. The G-LoSA source code is freely available at http://im.bioinformatics.ku.edu/GLoSA. PMID:23957286

Implementation of three dimensional conformal radiation therapy: prospects, opportunities, and challenges.

PubMed

Vijayakumar, S; Chen, G T

1995-12-01

To briefly review scientific rationale of 3D conformal radiation therapy (3DCRT) and discuss the prospects, opportunities, and challenges in the implementation of 3DCRT. Some of these ideas were discussed during a workshop on "Implementation of Three-Dimensional Conformal Radiation Therapy" in April 1994 at Bethesda, MD, and others have been discussed elsewhere in the literature. Local-regional control of cancer is an important component in the overall treatment strategy in any patient with cancer. It has been shown that failure to achieve local-regional control can lead to (a) an increase in chances of distant metastases, and (b) a decrease in the survival. In many disease sites, the doses delivered currently are inadequate to achieve satisfactory local tumor control rates; this is because in many sites, only limited doses of radiotherapy can be delivered due to the proximity of cancer to radiosensitive normal tissues. By conforming the radiotherapy beams to the tumor, doses to the tumors can be enhanced and doses to the normal tissues can be reduced. With the advances in 3DCRT, such conformation is possible now and is the rationale for using 3DCRT. However, a number of questions do remain that are not limited to the following: (a) What are the implications in terms of target volume definitions when implementing 3DCRT? (b) Are there some sites where research efforts can be focused to document the efficacy and cost effectiveness of 3DCRT? (c) How do we implement day-to-day 3DCRT treatment efficiently? (d) How do we transfer the technology from the university centers to the community without compromising quality? (e) What are all the quality assurance/quality improvement questions that need to be addressed and how do we ascertain quality assurance of 3DCRT? (f) Have we looked at cost-benefit ratios and quality of life (QOL) issues closely? There is a need for defining multiple target volumes: gross tumor volume, clinical target volume(s), and planning target volume(s). Such definitions should make implementation of 3DCRT more complex, yet will make high-dose delivery a possibility. There are many sites in which single and multiinstitutional studies are ongoing that include prostate, lung, head and neck, and brain. In other areas, cooperative group trials are required because of the inability of single institutions to accrue enough patients to answer clinically relevant questions with statistical validity. Although implementation of 3DCRT will require multiple steps, these multiple steps can be brought into clinical practice gradually and one does not have to wait until all steps required for implementation of 3DCRT are available. In this respect, "3DCRT" should be used in a very broad sense, from beam's eye view blocking, use of multibeam dose distribution, use of dose-volume histograms in choosing alternative plans, noncoplanar beam arrangements, intensity modulation, inverse planning, to totally automated implementation of 3DCRT. To transfer the 3DCRT capabilities to the community from the University Centers, there is a necessity to develop quality assurance programs. RTOG and the Three-Dimensional Oncology Group are spearheading these efforts. Three-dimensional conformal radiation therapy has potential not only to improve local control and decrease toxicity, but also to improve the cost benefit ratio in the use of radiotherapy as well as in improving quality of life in patients with cancer. Achieving many potential benefits of 3DCRT (improvement in local control, decreasing toxicity, organs-function preservation, improvement in cost effectiveness) will require further physics-related and clinical research in carefully conceived and successfully completed future clinical trials.

Bilateral Versus Unilateral Cochlear Implantation in Adult Listeners: Speech-On-Speech Masking and Multitalker Localization

PubMed Central

Buchholz, Jörg M.; Morgan, Catherine; Sharma, Mridula; Weller, Tobias; Konganda, Shivali Appaiah; Shirai, Kyoko; Kawano, Atsushi

2017-01-01

Binaural hearing helps normal-hearing listeners localize sound sources and understand speech in noise. However, it is not fully understood how far this is the case for bilateral cochlear implant (CI) users. To determine the potential benefits of bilateral over unilateral CIs, speech comprehension thresholds (SCTs) were measured in seven Japanese bilateral CI recipients using Helen test sentences (translated into Japanese) in a two-talker speech interferer presented from the front (co-located with the target speech), ipsilateral to the first-implanted ear (at +90° or −90°), and spatially symmetric at ±90°. Spatial release from masking was calculated as the difference between co-located and spatially separated SCTs. Localization was assessed in the horizontal plane by presenting either male or female speech or both simultaneously. All measurements were performed bilaterally and unilaterally (with the first implanted ear) inside a loudspeaker array. Both SCTs and spatial release from masking were improved with bilateral CIs, demonstrating mean bilateral benefits of 7.5 dB in spatially asymmetric and 3 dB in spatially symmetric speech mixture. Localization performance varied strongly between subjects but was clearly improved with bilateral over unilateral CIs with the mean localization error reduced by 27°. Surprisingly, adding a second talker had only a negligible effect on localization. PMID:28752811

From Diagnosis to Treatment: Clinical Applications of Nanotechnology in Thoracic Surgery.

PubMed

Digesu, Christopher S; Hofferberth, Sophie C; Grinstaff, Mark W; Colson, Yolonda L

2016-05-01

Nanotechnology is an emerging field with potential as an adjunct to cancer therapy, particularly thoracic surgery. Therapy can be delivered to tumors in a more targeted fashion, with less systemic toxicity. Nanoparticles may aid in diagnosis, preoperative characterization, and intraoperative localization of thoracic tumors and their lymphatics. Focused research into nanotechnology's ability to deliver both diagnostics and therapeutics has led to the development of nanotheranostics, which promises to improve the treatment of thoracic malignancies through enhanced tumor targeting, controlled drug delivery, and therapeutic monitoring. This article reviews nanoplatforms, their unique properties, and the potential for clinical application in thoracic surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Fiscal Shenanigans, Targeted Federal Health Care Funds, and Patient Mortality

PubMed Central

Baicker, Katherine; Staiger, Douglas

2007-01-01

We explore the effectiveness of matching grants when lower levels of government can expropriate some of the funds for other uses. Using data on the Medicaid Disproportionate Share program, we identify states that were most able to expropriate funds. Payments to public hospitals in these states were systematically diverted and had no significant impact on patient mortality. Payments that were not expropriated were associated with significant declines in patient mortality. Overall, subsidies were an effective mechanism for improving outcomes for the poor, but the impact was limited by the ability of state and local governments to divert the targeted funds. PMID:18084627

Contextual cueing in naturalistic scenes: Global and local contexts.

PubMed

Brockmole, James R; Castelhano, Monica S; Henderson, John M

2006-07-01

In contextual cueing, the position of a target within a group of distractors is learned over repeated exposure to a display with reference to a few nearby items rather than to the global pattern created by the elements. The authors contrasted the role of global and local contexts for contextual cueing in naturalistic scenes. Experiment 1 showed that learned target positions transfer when local information is altered but not when global information is changed. Experiment 2 showed that scene-target covariation is learned more slowly when local, but not global, information is repeated across trials than when global but not local information is repeated. Thus, in naturalistic scenes, observers are biased to associate target locations with global contexts. Copyright 2006 APA, all rights reserved.

Interventional Molecular Imaging.

PubMed

Solomon, Stephen B; Cornelis, Francois

2016-04-01

Although molecular imaging has had a dramatic impact on diagnostic imaging, it has only recently begun to be integrated into interventional procedures. Its significant impact is attributed to its ability to provide noninvasive, physiologic information that supplements conventional morphologic imaging. The four major interventional opportunities for molecular imaging are, first, to provide guidance to localize a target; second, to provide tissue analysis to confirm that the target has been reached; third, to provide in-room, posttherapy assessment; and fourth, to deliver targeted therapeutics. With improved understanding and application of(18)F-FDG, as well as the addition of new molecular probes beyond(18)F-FDG, the future holds significant promise for the expansion of molecular imaging into the realm of interventional procedures. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Challenges in realizing selectivity for nanoparticle biodistribution and clearance: lessons from gold nanoparticles.

PubMed

Haute, Desiree Van; Berlin, Jacob M

2017-08-01

The field of nanomedicine has received much attention for its potential to allow for targeted identification and treatment of tumors, while sparing healthy tissue. This promise has yet to be clinically realized; instead nanomedicine has translated into clinical benefit via formulations that improve the pharmacokinetics and toxicity profiles of toxic chemotherapeutic agents. In this perspective, we highlight that several of the defining strategies for using nanoparticles intravenously to target solid tumors have limited supporting data in animal studies. Namely, it does not appear that reducing macrophage (and other cell type) uptake in vitro leads to better biodistribution in vivo, nor does increasing blood circulation time nor active targeting. We suggest instead that the coming decade will primarily see nanoparticles impact immunotherapy and local/pseudolocal cancer therapy.

Automated metastatic brain lesion detection: a computer aided diagnostic and clinical research tool

NASA Astrophysics Data System (ADS)

Devine, Jeremy; Sahgal, Arjun; Karam, Irene; Martel, Anne L.

2016-03-01

The accurate localization of brain metastases in magnetic resonance (MR) images is crucial for patients undergoing stereotactic radiosurgery (SRS) to ensure that all neoplastic foci are targeted. Computer automated tumor localization and analysis can improve both of these tasks by eliminating inter and intra-observer variations during the MR image reading process. Lesion localization is accomplished using adaptive thresholding to extract enhancing objects. Each enhancing object is represented as a vector of features which includes information on object size, symmetry, position, shape, and context. These vectors are then used to train a random forest classifier. We trained and tested the image analysis pipeline on 3D axial contrast-enhanced MR images with the intention of localizing the brain metastases. In our cross validation study and at the most effective algorithm operating point, we were able to identify 90% of the lesions at a precision rate of 60%.

Contextual cost: when a visual-search target is not where it should be.

PubMed

Makovski, Tal; Jiang, Yuhong V

2010-02-01

Visual search is often facilitated when the search display occasionally repeats, revealing a contextual-cueing effect. According to the associative-learning account, contextual cueing arises from associating the display configuration with the target location. However, recent findings emphasizing the importance of local context near the target have given rise to the possibility that low-level repetition priming may account for the contextual-cueing effect. This study distinguishes associative learning from local repetition priming by testing whether search is directed toward a target's expected location, even when the target is relocated. After participants searched for a T among Ls in displays that repeated 24 times, they completed a transfer session where the target was relocated locally to a previously blank location (Experiment 1) or to an adjacent distractor location (Experiment 2). Results revealed that contextual cueing decreased as the target appeared farther away from its expected location, ultimately resulting in a contextual cost when the target swapped locations with a local distractor. We conclude that target predictability is a key factor in contextual cueing.

DOA Estimation for Underwater Wideband Weak Targets Based on Coherent Signal Subspace and Compressed Sensing

PubMed Central

2018-01-01

Direction of arrival (DOA) estimation is the basis for underwater target localization and tracking using towed line array sonar devices. A method of DOA estimation for underwater wideband weak targets based on coherent signal subspace (CSS) processing and compressed sensing (CS) theory is proposed. Under the CSS processing framework, wideband frequency focusing is accompanied by a two-sided correlation transformation, allowing the DOA of underwater wideband targets to be estimated based on the spatial sparsity of the targets and the compressed sensing reconstruction algorithm. Through analysis and processing of simulation data and marine trial data, it is shown that this method can accomplish the DOA estimation of underwater wideband weak targets. Results also show that this method can considerably improve the spatial spectrum of weak target signals, enhancing the ability to detect them. It can solve the problems of low directional resolution and unreliable weak-target detection in traditional beamforming technology. Compared with the conventional minimum variance distortionless response beamformers (MVDR), this method has many advantages, such as higher directional resolution, wider detection range, fewer required snapshots and more accurate detection for weak targets. PMID:29562642

Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand.

PubMed

Kularatne, Sumith A; Wang, Kevin; Santhapuram, Hari-Krishna R; Low, Philip S

2009-01-01

Prostate cancer (PCa) is a major cause of mortality and morbidity in Western society today. Current methods for detecting PCa are limited, leaving most early malignancies undiagnosed and sites of metastasis in advanced disease undetected. Major deficiencies also exist in the treatment of PCa, especially metastatic disease. In an effort to improve both detection and therapy of PCa, we have developed a PSMA-targeted ligand that delivers attached imaging and therapeutic agents selectively to PCa cells without targeting normal cells. The PSMA-targeted radioimaging agent (DUPA-(99m)Tc) was found to bind PSMA-positive human PCa cells (LNCaP cell line) with nanomolar affinity (K(D) = 14 nM). Imaging and biodistribution studies revealed that DUPA-(99m)Tc localizes primarily to LNCaP cell tumor xenografts in nu/nu mice (% injected dose/gram = 11.3 at 4 h postinjection; tumor-to-muscle ratio = 75:1). Two PSMA-targeted optical imaging agents (DUPA-FITC and DUPA-rhodamine B) were also shown to efficiently label PCa cells and to internalize and traffic to intracellular endosomes. A PSMA-targeted chemotherapeutic agent (DUPA-TubH) was demonstrated to kill PSMA-positive LNCaP cells in culture (IC(50) = 3 nM) and to eliminate established tumor xenografts in nu/nu mice with no detectable weight loss. Blockade of tumor targeting upon administration of excess PSMA inhibitor (PMPA) and the absence of targeting to PSMA-negative tumors confirmed the specificity of each of the above targeted reagents for PSMA. Tandem use of the imaging and therapeutic agents targeted to the same receptor could allow detection, staging, monitoring, and treatment of PCa with improved accuracy and efficacy.

Beat gestures improve word recall in 3- to 5-year-old children.

PubMed

Igualada, Alfonso; Esteve-Gibert, Núria; Prieto, Pilar

2017-04-01

Although research has shown that adults can benefit from the presence of beat gestures in word recall tasks, studies have failed to conclusively generalize these findings to preschool children. This study investigated whether the presence of beat gestures helps children to recall information when these gestures have the function of singling out a linguistic element in its discourse context. A total of 106 3- to 5-year-old children were asked to recall a list of words within a pragmatically child-relevant context (i.e., a storytelling activity) in which the target word was or was not accompanied by a beat gesture. Results showed that children recalled the target word significantly better when it was accompanied by a beat gesture than when it was not, indicating a local recall effect. Moreover, the recall of adjacent non-target words did not differ depending on the condition, revealing that beat gestures seem to have a strictly local highlighting function (i.e., no global recall effect). These results demonstrate that preschoolers benefit from the pragmatic contribution offered by beat gestures when they function as multimodal markers of prominence. Copyright © 2016 Elsevier Inc. All rights reserved.

A Novel Ship-Tracking Method for GF-4 Satellite Sequential Images.

PubMed

Yao, Libo; Liu, Yong; He, You

2018-06-22

The geostationary remote sensing satellite has the capability of wide scanning, persistent observation and operational response, and has tremendous potential for maritime target surveillance. The GF-4 satellite is the first geostationary orbit (GEO) optical remote sensing satellite with medium resolution in China. In this paper, a novel ship-tracking method in GF-4 satellite sequential imagery is proposed. The algorithm has three stages. First, a local visual saliency map based on local peak signal-to-noise ratio (PSNR) is used to detect ships in a single frame of GF-4 satellite sequential images. Second, the accuracy positioning of each potential target is realized by a dynamic correction using the rational polynomial coefficients (RPCs) and automatic identification system (AIS) data of ships. Finally, an improved multiple hypotheses tracking (MHT) algorithm with amplitude information is used to track ships by further removing the false targets, and to estimate ships’ motion parameters. The algorithm has been tested using GF-4 sequential images and AIS data. The results of the experiment demonstrate that the algorithm achieves good tracking performance in GF-4 satellite sequential images and estimates the motion information of ships accurately.

SmartRoads: training Indonesian workers to become road safety ambassadors in industrial and community settings.

PubMed

Montero, Kerry; Spencer, Graham; Ariens, Bernadette

2012-06-01

This paper reports on a programme to improve road safety awareness in an industrial community in the vicinity of Jakarta, in Indonesia. Adapting the model of a successful community and school-based programme in Victoria, in Australia, and using a peer education approach, 16 employees of a major manufacturing company were trained to implement road safety education programmes amongst their peers. Specific target groups for the educators were colleagues, schools and the local community. Over 2 days the employees, from areas as diverse as production, public relations, personnel services, administration and management, learned about road safety facts, causes of traffic casualties, prevention approaches and peer education strategies. They explored and developed strategies to use with their respective target groups and practised health education skills. The newly trained workers received certificates to acknowledge them as 'SmartRoads Ambassadors' and, with follow-up support and development, became road safety educators with a commitment and responsibility to deliver education to their respective work and local communities. This paper argues that the model has potential to provide an effective and locally relevant response to road safety issues in similar communities.

Combination of surface and borehole seismic data for robust target-oriented imaging

NASA Astrophysics Data System (ADS)

Liu, Yi; van der Neut, Joost; Arntsen, Børge; Wapenaar, Kees

2016-05-01

A novel application of seismic interferometry (SI) and Marchenko imaging using both surface and borehole data is presented. A series of redatuming schemes is proposed to combine both data sets for robust deep local imaging in the presence of velocity uncertainties. The redatuming schemes create a virtual acquisition geometry where both sources and receivers lie at the horizontal borehole level, thus only a local velocity model near the borehole is needed for imaging, and erroneous velocities in the shallow area have no effect on imaging around the borehole level. By joining the advantages of SI and Marchenko imaging, a macrovelocity model is no longer required and the proposed schemes use only single-component data. Furthermore, the schemes result in a set of virtual data that have fewer spurious events and internal multiples than previous virtual source redatuming methods. Two numerical examples are shown to illustrate the workflow and to demonstrate the benefits of the method. One is a synthetic model and the other is a realistic model of a field in the North Sea. In both tests, improved local images near the boreholes are obtained using the redatumed data without accurate velocities, because the redatumed data are close to the target.

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PubMed

Eisbruch, A; Dawson, L A; Kim, H M; Bradford, C R; Terrell, J E; Chepeha, D B; Teknos, T N; Anzai, Y; Marsh, L H; Martel, M K; Ten Haken, R K; Wolf, G T; Ship, J A

1999-01-01

To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Commonsense Investments in a Shared Future: Business Support of Public Schools. The New School Finance Research Agenda: Resource Utilization and School Districts. Finance Collaborative Working Paper #6.

ERIC Educational Resources Information Center

Lewis, Mary Ellen James

A decade ago, the business community began to pursue tentative, new relationships with schools; the focus was on long-term educational improvement, frequently targeted to core academic subjects. Now partnerships are everywhere, involving thousands of schools and hundreds of thousands of local people. This essay discusses the resources brought to…

An Investigation into the Impact of School Context on Achievement: A Situational Analysis of Five Western Cape Schools in South Africa

ERIC Educational Resources Information Center

Mushayikwa, Emmanuel

2009-01-01

The purpose of this study was to generate a snapshot profile of the teaching and learning environment in each of five schools in Cape Town, South Africa. The generated profile would in turn facilitate the identification of critical, localized and systemic factors that might be targeted by a whole school intervention programme to improve the…

Prolonged, brain-wide expression of nuclear-localized GCaMP3 for functional circuit mapping

PubMed Central

Kim, Christina K.; Miri, Andrew; Leung, Louis C.; Berndt, Andre; Mourrain, Philippe; Tank, David W.; Burdine, Rebecca D.

2014-01-01

Larval zebrafish offer the potential for large-scale optical imaging of neural activity throughout the central nervous system; however, several barriers challenge their utility. First, ~panneuronal probe expression has to date only been demonstrated at early larval stages up to 7 days post-fertilization (dpf), precluding imaging at later time points when circuits are more mature. Second, nuclear exclusion of genetically-encoded calcium indicators (GECIs) limits the resolution of functional fluorescence signals collected during imaging. Here, we report the creation of transgenic zebrafish strains exhibiting robust, nuclearly targeted expression of GCaMP3 across the brain up to at least 14 dpf utilizing a previously described optimized Gal4-UAS system. We confirmed both nuclear targeting and functionality of the modified probe in vitro and measured its kinetics in response to action potentials (APs). We then demonstrated in vivo functionality of nuclear-localized GCaMP3 in transgenic zebrafish strains by identifying eye position-sensitive fluorescence fluctuations in caudal hindbrain neurons during spontaneous eye movements. Our methodological approach will facilitate studies of larval zebrafish circuitry by both improving resolution of functional Ca2+ signals and by allowing brain-wide expression of improved GECIs, or potentially any probe, further into development. PMID:25505384

Fine-grained, local maps and coarse, global representations support human spatial working memory.

PubMed

Katshu, Mohammad Zia Ul Haq; d'Avossa, Giovanni

2014-01-01

While sensory processes are tuned to particular features, such as an object's specific location, color or orientation, visual working memory (vWM) is assumed to store information using representations, which generalize over a feature dimension. Additionally, current vWM models presume that different features or objects are stored independently. On the other hand, configurational effects, when observed, are supposed to mainly reflect encoding strategies. We show that the location of the target, relative to the display center and boundaries, and overall memory load influenced recall precision, indicating that, like sensory processes, capacity limited vWM resources are spatially tuned. When recalling one of three memory items the target distance from the display center was overestimated, similar to the error when only one item was memorized, but its distance from the memory items' average position was underestimated, showing that not only individual memory items' position, but also the global configuration of the memory array may be stored. Finally, presenting the non-target items at recall, consequently providing landmarks and configurational information, improved precision and accuracy of target recall. Similarly, when the non-target items were translated at recall, relative to their position in the initial display, a parallel displacement of the recalled target was observed. These findings suggest that fine-grained spatial information in vWM is represented in local maps whose resolution varies with distance from landmarks, such as the display center, while coarse representations are used to store the memory array configuration. Both these representations are updated at the time of recall.

Fine-Grained, Local Maps and Coarse, Global Representations Support Human Spatial Working Memory

PubMed Central

Katshu, Mohammad Zia Ul Haq; d'Avossa, Giovanni

2014-01-01

While sensory processes are tuned to particular features, such as an object's specific location, color or orientation, visual working memory (vWM) is assumed to store information using representations, which generalize over a feature dimension. Additionally, current vWM models presume that different features or objects are stored independently. On the other hand, configurational effects, when observed, are supposed to mainly reflect encoding strategies. We show that the location of the target, relative to the display center and boundaries, and overall memory load influenced recall precision, indicating that, like sensory processes, capacity limited vWM resources are spatially tuned. When recalling one of three memory items the target distance from the display center was overestimated, similar to the error when only one item was memorized, but its distance from the memory items' average position was underestimated, showing that not only individual memory items' position, but also the global configuration of the memory array may be stored. Finally, presenting the non-target items at recall, consequently providing landmarks and configurational information, improved precision and accuracy of target recall. Similarly, when the non-target items were translated at recall, relative to their position in the initial display, a parallel displacement of the recalled target was observed. These findings suggest that fine-grained spatial information in vWM is represented in local maps whose resolution varies with distance from landmarks, such as the display center, while coarse representations are used to store the memory array configuration. Both these representations are updated at the time of recall. PMID:25259601

Adult soft tissue sarcomas: conventional therapies and molecularly targeted approaches.

PubMed

Mocellin, Simone; Rossi, Carlo R; Brandes, Alba; Nitti, Donato

2006-02-01

The therapeutic approach to soft tissue sarcomas (STS) has evolved over the past two decades based on the results from randomized controlled trials, which are guiding physicians in the treatment decision-making process. Despite significant improvements in the control of local disease, a significant number of patients ultimately die of recurrent/metastatic disease following radical surgery due to a lack of effective adjuvant treatments. In addition, the characteristic chemoresistance of STS has compromised the therapeutic value of conventional antineoplastic agents in cases of unresectable advanced/metastatic disease. Therefore, novel therapeutic strategies are urgently needed to improve the prognosis of patients with STS. Recent advances in STS biology are paving the way to the development of molecularly targeted therapeutic strategies, the efficacy of which relies not only on the knowledge of the molecular mechanisms underlying cancer development/progression but also on the personalization of the therapeutic regimen according to the molecular features of individual tumours. In this work, we review the state-of-the-art of conventional treatments for STS and summarize the most promising findings in the development of molecularly targeted therapeutic approaches.

Medication-use evaluation with a Web application.

PubMed

Burk, Muriel; Moore, Von; Glassman, Peter; Good, Chester B; Emmendorfer, Thomas; Leadholm, Thomas C; Cunningham, Francesca

2013-12-15

A Web-based application for coordinating medication-use evaluation (MUE) initiatives within the Veterans Affairs (VA) health care system is described. The MUE Tracker (MUET) software program was created to improve VA's ability to conduct national medication-related interventions throughout its network of 147 medical centers. MUET initiatives are centrally coordinated by the VA Center for Medication Safety (VAMedSAFE), which monitors the agency's integrated databases for indications of suboptimal prescribing or drug therapy monitoring and adverse treatment outcomes. When a pharmacovigilance signal is detected, VAMedSAFE identifies "trigger groups" of at-risk veterans and uploads patient lists to the secure MUET application, where locally designated personnel (typically pharmacists) can access and use the data to target risk-reduction efforts. Local data on patient-specific interventions are stored in a centralized database and regularly updated to enable tracking and reporting for surveillance and quality-improvement purposes; aggregated data can be further analyzed for provider education and benchmarking. In a three-year pilot project, the MUET program was found effective in promoting improved prescribing of erythropoiesis-stimulating agents (ESAs) and enhanced laboratory monitoring of ESA-treated patients in all specified trigger groups. The MUET initiative has since been expanded to target other high-risk drugs, and efforts are underway to refine the tool for broader utility. The MUET application has enabled the increased standardization of medication safety initiatives across the VA system and may serve as a useful model for the development of pharmacovigilance tools by other large integrated health care systems.

Comparison of radiofrequency body coils for MRI at 3 Tesla: a simulation study using parallel transmission on various anatomical targets

PubMed Central

Wu, Xiaoping; Zhang, Xiaotong; Tian, Jinfeng; Schmitter, Sebastian; Hanna, Brian; Strupp, John; Pfeuffer, Josef; Hamm, Michael; Wang, Dingxin; Nistler, Juergen; He, Bin; Vaughan, J. Thomas; Ugurbil, Kamil; Van de Moortele, Pierre-Francois

2015-01-01

The performance of multichannel transmit coil layouts and parallel transmission (pTx) radiofrequency (RF) pulse design was evaluated with respect to transmit B1 (B1+) homogeneity and Specific Absorption Rate (SAR) at 3 Tesla for a whole body coil. Five specific coils were modeled and compared: a 32-rung birdcage body coil (driven either in a fixed quadrature mode or a two-channel transmit mode), two single-ring stripline arrays (with either 8 or 16 elements), and two multi-ring stripline arrays (with 2 or 3 identical rings, stacked in the z-axis and each comprising eight azimuthally distributed elements). Three anatomical targets were considered, each defined by a 3D volume representative of a meaningful region of interest (ROI) in routine clinical applications. For a given anatomical target, global or local SAR controlled pTx pulses were designed to homogenize RF excitation within the ROI. At the B1+ homogeneity achieved by the quadrature driven birdcage design, pTx pulses with multichannel transmit coils achieved up to ~8 fold reduction in local and global SAR. When used for imaging head and cervical spine or imaging thoracic spine, the double-ring array outperformed all coils including the single-ring arrays. While the advantage of the double-ring array became much less pronounced for pelvic imaging with a substantially larger ROI, the pTx approach still provided significant gains over the quadrature birdcage coil. For all design scenarios, using the 3-ring array did not necessarily improve the RF performance. Our results suggest that pTx pulses with multichannel transmit coils can reduce local and global SAR substantially for body coils while attaining improved B1+ homogeneity, particularly for a “z-stacked” double-ring design with coil elements arranged on two transaxial rings. PMID:26332290

Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer

NASA Astrophysics Data System (ADS)

Hoang, Nu Bryan

Block copolymer micelles have emerged as a viable formulation strategy with several drugs relying on this technology in clinical evaluation. To date, information on the tumor penetration and intratumoral distribution of block copolymer micelles (BCM) has been quite limited. Thus, there is impetus to develop a radiolabeled formulation that can be used to gain invaluable insight into the intratumoral distribution of the BCMs. This information could then be used to direct formulation strategies as a means to optimize treatment outcomes. This thesis describes the synthesis and characterization of a targeted block copolymer micelle system based on poly(ethylene glycol)-block -poly(epsilon-caprolactone) labeled with the radionuclide Indium-111 (111In). The incorporation of the imageable component, 111In permits pursuit of image-guided drug delivery for real-time monitoring of tumor localization and intratumoral distribution. Intracellular trafficking of drugs and therapies such as Auger electron emitting radionuclides to perinuclear and nuclear regions of cells is critical to realizing their full therapeutic potential. HER2 specific antibodies (trastuzumab fab fragments) and nuclear localization signal peptides were conjugated to the surface of the BCMs to direct uptake in HER2 expressing cells and subsequent localization in the cell nucleus. Cell uptake was HER2 density dependent, confirming receptor-mediated internalization of the BCMs. Importantly, conjugation of NLS resulted in a significant increase in nuclear uptake of the radionuclide 111In. Successful nuclear targeting was shown to improve the antiproliferative effect of the Auger electrons. In addition, a significant radiation enhancement effect was observed by concurrent delivery of low-dose MTX and 111In in all breast cancer cell lines evaluated. Imaging enabled the accurate quantification of the specific tumor uptake of the micelles and visualization of their degree of tumor penetration in relation to microvessel density. Ultimately, the 111In-micelles could be used for such diverse applications as detection of malignancies, molecular characterization of tumors, improved therapy guidance and targeted anti-cancer treatment.

Optimal Quantization Scheme for Data-Efficient Target Tracking via UWSNs Using Quantized Measurements.

PubMed

Zhang, Senlin; Chen, Huayan; Liu, Meiqin; Zhang, Qunfei

2017-11-07

Target tracking is one of the broad applications of underwater wireless sensor networks (UWSNs). However, as a result of the temporal and spatial variability of acoustic channels, underwater acoustic communications suffer from an extremely limited bandwidth. In order to reduce network congestion, it is important to shorten the length of the data transmitted from local sensors to the fusion center by quantization. Although quantization can reduce bandwidth cost, it also brings about bad tracking performance as a result of information loss after quantization. To solve this problem, this paper proposes an optimal quantization-based target tracking scheme. It improves the tracking performance of low-bit quantized measurements by minimizing the additional covariance caused by quantization. The simulation demonstrates that our scheme performs much better than the conventional uniform quantization-based target tracking scheme and the increment of the data length affects our scheme only a little. Its tracking performance improves by only 4.4% from 2- to 3-bit, which means our scheme weakly depends on the number of data bits. Moreover, our scheme also weakly depends on the number of participate sensors, and it can work well in sparse sensor networks. In a 6 × 6 × 6 sensor network, compared with 4 × 4 × 4 sensor networks, the number of participant sensors increases by 334.92%, while the tracking accuracy using 1-bit quantized measurements improves by only 50.77%. Overall, our optimal quantization-based target tracking scheme can achieve the pursuit of data-efficiency, which fits the requirements of low-bandwidth UWSNs.

Toyota production system quality improvement initiative improves perioperative antibiotic therapy.

PubMed

Burkitt, Kelly H; Mor, Maria K; Jain, Rajiv; Kruszewski, Matthew S; McCray, Ellesha E; Moreland, Michael E; Muder, Robert R; Obrosky, David Scott; Sevick, Mary Ann; Wilson, Mark A; Fine, Michael J

2009-09-01

To assess the role of a Toyota production system (TPS) quality improvement (QI) intervention on appropriateness of perioperative antibiotic therapy and in length of hospital stay (LOS) among surgical patients. Pre-post quasi-experimental study using local and national retrospective cohorts. We used TPS methods to implement a multifaceted intervention to reduce nosocomial methicillin-resistant Staphylococcus aureus infections on a Veterans Affairs surgical unit, which led to a QI intervention targeting appropriate perioperative antibiotic prophylaxis. Appropriate perioperative antibiotic therapy was defined as selection of the recommended antibiotic agents for a duration not exceeding 24 hours from the time of the operation. The local computerized medical record system was used to identify patients undergoing the 25 most common surgical procedures and to examine changes in appropriate antibiotic therapy and LOS over time. Overall, 2550 surgical admissions were identified from the local computerized medical records. The proportion of surgical admissions receiving appropriate perioperative antibiotics was significantly higher (P <.01) in 2004 after initiation of the TPS intervention (44.0%) compared with the previous 4 years (range, 23.4%-29.8%) primarily because of improvements in compliance with antibiotic therapy duration rather than appropriate antibiotic selection. There was no statistically significant decrease in LOS over time. The use of TPS methods resulted in a QI intervention that was associated with an increase in appropriate perioperative antibiotic therapy among surgical patients, without affecting LOS.

Metrology Camera System Using Two-Color Interferometry

NASA Technical Reports Server (NTRS)

Dubovitsky, Serge; Liebe, Carl Christian; Peters, Robert; Lay, Oliver

2007-01-01

A metrology system that contains no moving parts simultaneously measures the bearings and ranges of multiple reflective targets in its vicinity, enabling determination of the three-dimensional (3D) positions of the targets with submillimeter accuracy. The system combines a direction-measuring metrology camera and an interferometric range-finding subsystem. Because the system is based partly on a prior instrument denoted the Modulation Sideband Technology for Absolute Ranging (MSTAR) sensor and because of its 3D capability, the system is denoted the MSTAR3D. Developed for use in measuring the shape (for the purpose of compensating for distortion) of large structures like radar antennas, it can also be used to measure positions of multiple targets in the course of conventional terrestrial surveying. A diagram of the system is shown in the figure. One of the targets is a reference target having a known, constant distance with respect to the system. The system comprises a laser for generating local and target beams at a carrier frequency; a frequency shifting unit to introduce a frequency shift offset between the target and local beams; a pair of high-speed modulators that apply modulation to the carrier frequency in the local and target beams to produce a series of modulation sidebands, the highspeed modulators having modulation frequencies of FL and FM; a target beam launcher that illuminates the targets with the target beam; optics and a multipixel photodetector; a local beam launcher that launches the local beam towards the multi-pixel photodetector; a mirror for projecting to the optics a portion of the target beam reflected from the targets, the optics being configured to focus the portion of the target beam at the multi-pixel photodetector; and a signal-processing unit connected to the photodetector. The portion of the target beam reflected from the targets produces spots on the multi-pixel photodetector corresponding to the targets, respectively, and the signal-processing unit centroids the spots to determine bearings of the targets, respectively. As the spots oscillate in intensity because they are mixed with the local laser beam that is flood illuminating the focal plane, the phase of oscillation of each spot is measured, the phase of sidebands in the oscillation of each spot being proportional to a distance to the corresponding target relative to the reference target A.

Efficient Nonlocal M-Control and N-Target Controlled Unitary Gate Using Non-symmetric GHZ States

NASA Astrophysics Data System (ADS)

Chen, Li-Bing; Lu, Hong

2018-03-01

Efficient local implementation of a nonlocal M-control and N-target controlled unitary gate is considered. We first show that with the assistance of two non-symmetric qubit(1)-qutrit(N) Greenberger-Horne-Zeilinger (GHZ) states, a nonlocal 2-control and N-target controlled unitary gate can be constructed from 2 local two-qubit CNOT gates, 2 N local two-qutrit conditional SWAP gates, N local qutrit-qubit controlled unitary gates, and 2 N single-qutrit gates. At each target node, the two third levels of the two GHZ target qutrits are used to expose one and only one initial computational state to the local qutrit-qubit controlled unitary gate, instead of being used to hide certain states from the conditional dynamics. This scheme can be generalized straightforwardly to implement a higher-order nonlocal M-control and N-target controlled unitary gate by using M non-symmetric qubit(1)-qutrit(N) GHZ states as quantum channels. Neither the number of the additional levels of each GHZ target particle nor that of single-qutrit gates needs to increase with M. For certain realistic physical systems, the total gate time may be reduced compared with that required in previous schemes.

Impact localization on composite structures using time difference and MUSIC approach

NASA Astrophysics Data System (ADS)

Zhong, Yongteng; Xiang, Jiawei

2017-05-01

1-D uniform linear array (ULA) has the shortcoming of the half-plane mirror effect, which does not allow discriminating between a target placed above the array and a target placed below the array. This paper presents time difference (TD) and multiple signal classification (MUSIC) based omni-directional impact localization on a large stiffened composite structure using improved linear array, which is able to perform omni-directional 360° localization. This array contains 2M+3 PZT sensors, where 2M+1 PZT sensors are arranged as a uniform linear array, and the other two PZT sensors are placed above and below the array. Firstly, the arrival times of impact signals observed by the other two sensors are determined using the wavelet transform. Compared with each other, the direction range of impact source can be decided in general, 0°to 180° or 180°to 360°. And then, two dimensional multiple signal classification (2D-MUSIC) based spatial spectrum formula using the uniform linear array is applied for impact localization by the general direction range. When the arrival times of impact signals observed by upper PZT is equal to that of lower PZT, the direction can be located in x axis (0°or 180°). And time difference based MUSIC method is present to locate impact position. To verify the proposed approach, the proposed approach is applied to a composite structure. The localization results are in good agreement with the actual impact occurring positions.

Localized Cell and Drug Delivery for Auditory Prostheses

PubMed Central

Hendricks, Jeffrey L.; Chikar, Jennifer A.; Crumling, Mark A.; Raphael, Yehoash; Martin, David C.

2011-01-01

Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness. PMID:18573323

Advanced Demonstration of Motion Correction for Ship-to-Ship Passive Inspections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ziock, Klaus-Peter; Boehnen, Chris Bensing; Ernst, Joseph

2013-09-30

Passive radiation detection is a key tool for detecting illicit nuclear materials. In maritime applications it is most effective against small vessels where attenuation is of less concern. Passive imaging provides: discrimination between localized (threat) and distributed (non-threat) sources, removal of background fluctuations due to nearby shorelines and structures, source localization to an individual craft in crowded waters, and background subtracted spectra. Unfortunately, imaging methods cannot be easily applied in ship-to-ship inspections because relative motion of the vessels blurs the results over many pixels, significantly reducing sensitivity. This is particularly true for the smaller water craft where passive inspections aremore » most valuable. In this project we performed tests and improved the performance of an instrument (developed earlier under, “Motion Correction for Ship-to-Ship Passive Inspections”) that uses automated tracking of a target vessel in visible-light images to generate a 3D radiation map of the target vessel from data obtained using a gamma-ray imager.« less

Lake and wetland ecosystem services measuring water storage and local climate regulation

NASA Astrophysics Data System (ADS)

Wong, Christina P.; Jiang, Bo; Bohn, Theodore J.; Lee, Kai N.; Lettenmaier, Dennis P.; Ma, Dongchun; Ouyang, Zhiyun

2017-04-01

Developing interdisciplinary methods to measure ecosystem services is a scientific priority, however, progress remains slow in part because we lack ecological production functions (EPFs) to quantitatively link ecohydrological processes to human benefits. In this study, we tested a new approach, combining a process-based model with regression models, to create EPFs to evaluate water storage and local climate regulation from a green infrastructure project on the Yongding River in Beijing, China. Seven artificial lakes and wetlands were established to improve local water storage and human comfort; evapotranspiration (ET) regulates both services. Managers want to minimize the trade-off between water losses and cooling to sustain water supplies while lowering the heat index (HI) to improve human comfort. We selected human benefit indicators using water storage targets and Beijing's HI, and the Variable Infiltration Capacity model to determine the change in ET from the new ecosystems. We created EPFs to quantify the ecosystem services as marginal values [Δfinal ecosystem service/Δecohydrological process]: (1) Δwater loss (lake evaporation/volume)/Δdepth and (2) Δsummer HI/ΔET. We estimate the new ecosystems increased local ET by 0.7 mm/d (20.3 W/m2) on the Yongding River. However, ET rates are causing water storage shortfalls while producing no improvements in human comfort. The shallow lakes/wetlands are vulnerable to drying when inflow rates fluctuate, low depths lead to higher evaporative losses, causing water storage shortfalls with minimal cooling effects. We recommend managers make the lakes deeper to increase water storage, and plant shade trees to improve human comfort in the parks.

Sphincter-sparing local excision and hypofractionated radiation therapy for anorectal melanoma: a 20-year experience.

PubMed

Kelly, Patrick; Zagars, Gunar K; Cormier, Jancie N; Ross, Merrick I; Guadagnolo, B Ashleigh

2011-10-15

Anorectal melanoma is a rare disease with a poor prognosis. Because survival is determined by distant failure, many centers have adopted sphincter-sparing excision for primary tumor control. However, this approach is associated with high rates of local failure (∼50%). In this study, the authors report their 20-year experience with sphincter-sparing excision combined with radiation therapy (RT) for the treatment of localized anorectal melanoma. The authors reviewed the records of 54 patients with localized anorectal melanoma who were treated at the University of Texas MD Anderson Cancer Center from 1989 to 2008. All patients underwent definitive local excision with or without sentinel lymph node biopsy or lymph node dissection. RT (25-36 grays in 5-6 fractions) was delivered to extended fields that targeted the primary site and draining pelvic/inguinal lymphatics in 39 patients and to limited fields that targeted only the primary site in 15 patients. The 5-year rates of local control (LC), lymph node control (NC), and sphincter preservation were 82%, 88%, and 96%, respectively. However, because of the high rate of distant metastasis, the overall survival (OS) rate at 5 years was only 30%. Although there were no significant differences in LC, NC, or OS based on RT field extent, patients who received extended-field RT had higher rates of lymphedema than patients who received limited-field RT. The current results indicated that combined sphincter-sparing local excision and RT is a well tolerated approach that provides effective LC for patients with anorectal melanoma. Inclusion of the inguinal lymph node basins in the RT fields did not improve outcomes and was associated with an increased risk of lymphedema. Copyright © 2011 American Cancer Society.

Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy.

PubMed

Nogueira-Librelotto, Daniele R; Codevilla, Cristiane F; Farooqi, Ammad; Rolim, Clarice M B

2017-01-01

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Target thrust measurement for applied-field magnetoplasmadynamic thruster

NASA Astrophysics Data System (ADS)

Wang, B.; Yang, W.; Tang, H.; Li, Z.; Kitaeva, A.; Chen, Z.; Cao, J.; Herdrich, G.; Zhang, K.

2018-07-01

In this paper, we present a flat target thrust stand which is designed to measure the thrust of a steady-state applied-field magnetoplasmadynamic thruster (AF-MPDT). In our experiments we varied target-thruster distances and target size to analyze their influence on the target thrust measurement results. The obtained thrust-distance curves increase to local maximum and then decreases with the increasing distance, which means that the plume of the AF-MPDT can still accelerate outside the thruster exit. The peak positions are related to the target sizes: larger targets can make the peak positions further from the thruster and decrease the measurement errors. To further improve the reliability of measurement results, a thermal equilibrium assumption combined with Knudsen’s cosine law is adapted to analyze the error caused by the back stream of plume particles. Under the assumption, the error caused by particle backflow is no more than 3.6% and the largest difference between the measured thrust and the theoretical thrust is 14%. Moreover, it was verified that target thrust measurement can disturb the working of the AF-MPD thruster, and the influence on the thrust measurement result is no more than 1% in our experiment.

Image Guidance in External Beam Accelerated Partial Breast Irradiation: Comparison of Surrogates for the Lumpectomy Cavity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasan, Yasmin; Kim, Leonard; Martinez, Alvaro

Purpose: To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. Methods and Materials: Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: (1) to bony anatomy, (2) to the center of mass (COM) of surgical clips, and (3) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs ({delta}COM{sub Bone}, {delta}COM{sub Clips}, and {delta}COM{sub Surface}) were determined. Smaller {delta}COMs were interpreted as bettermore » localizations. Correlation coefficients were calculated for {delta}COM vs. several variables. Results: The {delta}COM{sub Bone} (mean, 7 {+-} 2 [SD] mm) increased with breast volume (r = 0.4; p = 0.02) and distance from the chest wall (r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization ({delta}COM{sub Clips} < {delta}COM{sub Bone}) in 25 of 27 cases. Breast surface matching improved cavity localization ({delta}COM{sub Surface} < {delta}COM{sub Bone}) in 19 of 27 cases. Mean improvements ({delta}COM{sub Bone} - {delta}COM{sub ClipsorSurface}) were 4 {+-} 3 and 2 {+-} 4 mm, respectively. In terms of percentage of improvement ([{delta}COM{sub Bone} - {delta}COM{sub ClipsorSurface}]/{delta}COM{sub Bone}), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. Conclusions: Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable.« less

Sustained Attention to Local and Global Target Features Is Different: Performance and Tympanic Membrane Temperature

ERIC Educational Resources Information Center

Helton, William S.; Hayrynen, Lauren; Schaeffer, David

2009-01-01

Vision researchers have investigated the differences between global and local feature perception. No one has, however, examined the role of global and local feature discrimination in sustained attention tasks. In this experiment participants performed a sustained attention task requiring either global or local letter target discriminations or…

Implementation of a guideline for local health policy making by regional health services: exploring determinants of use by a web survey.

PubMed

Kuunders, Theo J M; Jacobs, Monique A M; Goor, Ien A M van de; Bon-Martens, Marja J H van; Oers, Hans A M van; Paulussen, Theo G W M

2017-08-15

Previous evaluation showed insufficient use of a national guideline for integrated local health policy by Regional Health Services (RHS) in the Netherlands. The guideline focuses on five health topics and includes five checklists to support integrated municipal health policies. This study explores the determinants of guideline use by regional Dutch health professionals. A web survey was send to 304 RHS health professionals. The questionnaire was based on a theory- and research-based framework of determinants of public health innovations. Main outcomes were guideline use and completeness of use, defined as the number of health topics and checklists used. Associations between determinants and (completeness of) guideline use were explored by multivariate regression models. The survey was started by 120 professionals (39%). Finally, results from 73 respondents (24%) were eligible for analyses. All 28 Dutch RHS organizations were represented in the final dataset. About half of the respondents (48%) used the guideline. The average score for completeness of use (potential range 1-10) was 2.37 (sd = 1.78; range 1-7). Knowledge, perceived task responsibility and usability were significantly related to guideline use in univariate analyses. Only usability remained significant in the multivariate model on guideline use. Only self-efficacy accounted for significant proportions of variance in completeness of use. The results imply that strategies to improve guideline use by RHSs should primarily target perceived usability. Self-efficacy appeared the primary target for improving completeness of guideline use. Methods for targeting these determinants in RHSs are discussed.

Dual-threshold segmentation using Arimoto entropy based on chaotic bee colony optimization

NASA Astrophysics Data System (ADS)

Li, Li

2018-03-01

In order to extract target from complex background more quickly and accurately, and to further improve the detection effect of defects, a method of dual-threshold segmentation using Arimoto entropy based on chaotic bee colony optimization was proposed. Firstly, the method of single-threshold selection based on Arimoto entropy was extended to dual-threshold selection in order to separate the target from the background more accurately. Then intermediate variables in formulae of Arimoto entropy dual-threshold selection was calculated by recursion to eliminate redundant computation effectively and to reduce the amount of calculation. Finally, the local search phase of artificial bee colony algorithm was improved by chaotic sequence based on tent mapping. The fast search for two optimal thresholds was achieved using the improved bee colony optimization algorithm, thus the search could be accelerated obviously. A large number of experimental results show that, compared with the existing segmentation methods such as multi-threshold segmentation method using maximum Shannon entropy, two-dimensional Shannon entropy segmentation method, two-dimensional Tsallis gray entropy segmentation method and multi-threshold segmentation method using reciprocal gray entropy, the proposed method can segment target more quickly and accurately with superior segmentation effect. It proves to be an instant and effective method for image segmentation.

Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore

PubMed Central

Marquardt, Joseph R.; Perkins, Jennifer L.; Beuoy, Kyle J.; Fisk, Harold A.

2016-01-01

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus. PMID:27339139

Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore.

PubMed

Marquardt, Joseph R; Perkins, Jennifer L; Beuoy, Kyle J; Fisk, Harold A

2016-07-12

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus.

A physics-based solver to optimize the illumination of cylindrical targets in spherically distributed high power laser systems.

PubMed

Gourdain, P-A

2017-05-01

In recent years, our understanding of high energy density plasmas has played an important role in improving inertial fusion confinement and in emerging new fields of physics, such as laboratory astrophysics. Every new idea required developing innovative experimental platforms at high power laser facilities, such as OMEGA or NIF. These facilities, designed to focus all their beams onto spherical targets or hohlraum windows, are now required to shine them on more complex targets. While the pointing on planar geometries is relatively straightforward, it becomes problematic for cylindrical targets or target with more complex geometries. This publication describes how the distribution of laser beams on a cylindrical target can be done simply by using a set of physical laws as a pointing procedure. The advantage of the method is threefold. First, it is straightforward, requiring no mathematical enterprise besides solving ordinary differential equations. Second, it will converge if a local optimum exists. Finally, it is computationally inexpensive. Experimental results show that this approach produces a geometrical beam distribution that yields cylindrically symmetric implosions.

A physics-based solver to optimize the illumination of cylindrical targets in spherically distributed high power laser systems

NASA Astrophysics Data System (ADS)

Gourdain, P.-A.

2017-05-01

In recent years, our understanding of high energy density plasmas has played an important role in improving inertial fusion confinement and in emerging new fields of physics, such as laboratory astrophysics. Every new idea required developing innovative experimental platforms at high power laser facilities, such as OMEGA or NIF. These facilities, designed to focus all their beams onto spherical targets or hohlraum windows, are now required to shine them on more complex targets. While the pointing on planar geometries is relatively straightforward, it becomes problematic for cylindrical targets or target with more complex geometries. This publication describes how the distribution of laser beams on a cylindrical target can be done simply by using a set of physical laws as a pointing procedure. The advantage of the method is threefold. First, it is straightforward, requiring no mathematical enterprise besides solving ordinary differential equations. Second, it will converge if a local optimum exists. Finally, it is computationally inexpensive. Experimental results show that this approach produces a geometrical beam distribution that yields cylindrically symmetric implosions.

Developing a targeted, theory-informed implementation intervention using two theoretical frameworks to address health professional and organisational factors: a case study to improve the management of mild traumatic brain injury in the emergency department.

PubMed

Tavender, Emma J; Bosch, Marije; Gruen, Russell L; Green, Sally E; Michie, Susan; Brennan, Sue E; Francis, Jill J; Ponsford, Jennie L; Knott, Jonathan C; Meares, Sue; Smyth, Tracy; O'Connor, Denise A

2015-05-25

Despite the availability of evidence-based guidelines for the management of mild traumatic brain injury in the emergency department (ED), variations in practice exist. Interventions designed to implement recommended behaviours can reduce this variation. Using theory to inform intervention development is advocated; however, there is no consensus on how to select or apply theory. Integrative theoretical frameworks, based on syntheses of theories and theoretical constructs relevant to implementation, have the potential to assist in the intervention development process. This paper describes the process of applying two theoretical frameworks to investigate the factors influencing recommended behaviours and the choice of behaviour change techniques and modes of delivery for an implementation intervention. A stepped approach was followed: (i) identification of locally applicable and actionable evidence-based recommendations as targets for change, (ii) selection and use of two theoretical frameworks for identifying barriers to and enablers of change (Theoretical Domains Framework and Model of Diffusion of Innovations in Service Organisations) and (iii) identification and operationalisation of intervention components (behaviour change techniques and modes of delivery) to address the barriers and enhance the enablers, informed by theory, evidence and feasibility/acceptability considerations. We illustrate this process in relation to one recommendation, prospective assessment of post-traumatic amnesia (PTA) by ED staff using a validated tool. Four recommendations for managing mild traumatic brain injury were targeted with the intervention. The intervention targeting the PTA recommendation consisted of 14 behaviour change techniques and addressed 6 theoretical domains and 5 organisational domains. The mode of delivery was informed by six Cochrane reviews. It was delivered via five intervention components : (i) local stakeholder meetings, (ii) identification of local opinion leader teams, (iii) a train-the-trainer workshop for appointed local opinion leaders, (iv) local training workshops for delivery by trained local opinion leaders and (v) provision of tools and materials to prompt recommended behaviours. Two theoretical frameworks were used in a complementary manner to inform intervention development in managing mild traumatic brain injury in the ED. The effectiveness and cost-effectiveness of the developed intervention is being evaluated in a cluster randomised trial, part of the Neurotrauma Evidence Translation (NET) program.

Nuclear Localization of Haa1, Which Is Linked to Its Phosphorylation Status, Mediates Lactic Acid Tolerance in Saccharomyces cerevisiae

PubMed Central

Sugiyama, Minetaka; Akase, Shin-Pei; Nakanishi, Ryota; Horie, Hitoshi; Kaneko, Yoshinobu

2014-01-01

Improvement of the lactic acid resistance of the yeast Saccharomyces cerevisiae is important for the application of the yeast in industrial production of lactic acid from renewable resources. However, we still do not know the precise mechanisms of the lactic acid adaptation response in yeast and, consequently, lack effective approaches for improving its lactic acid tolerance. To enhance our understanding of the adaptation response, we screened for S. cerevisiae genes that confer enhanced lactic acid resistance when present in multiple copies and identified the transcriptional factor Haa1 as conferring resistance to toxic levels of lactic acid when overexpressed. The enhanced tolerance probably results from increased expression of its target genes. When cells that expressed Haa1 only from the endogenous promoter were exposed to lactic acid stress, the main subcellular localization of Haa1 changed from the cytoplasm to the nucleus within 5 min. This nuclear accumulation induced upregulation of the Haa1 target genes YGP1, GPG1, and SPI1, while the degree of Haa1 phosphorylation observed under lactic acid-free conditions decreased. Disruption of the exportin gene MSN5 led to accumulation of Haa1 in the nucleus even when no lactic acid was present. Since Msn5 was reported to interact with Haa1 and preferentially exports phosphorylated cargo proteins, our results suggest that regulation of the subcellular localization of Haa1, together with alteration of its phosphorylation status, mediates the adaptation to lactic acid stress in yeast. PMID:24682296

Infrared image background modeling based on improved Susan filtering

NASA Astrophysics Data System (ADS)

Yuehua, Xia

2018-02-01

When SUSAN filter is used to model the infrared image, the Gaussian filter lacks the ability of direction filtering. After filtering, the edge information of the image cannot be preserved well, so that there are a lot of edge singular points in the difference graph, increase the difficulties of target detection. To solve the above problems, the anisotropy algorithm is introduced in this paper, and the anisotropic Gauss filter is used instead of the Gauss filter in the SUSAN filter operator. Firstly, using anisotropic gradient operator to calculate a point of image's horizontal and vertical gradient, to determine the long axis direction of the filter; Secondly, use the local area of the point and the neighborhood smoothness to calculate the filter length and short axis variance; And then calculate the first-order norm of the difference between the local area of the point's gray-scale and mean, to determine the threshold of the SUSAN filter; Finally, the built SUSAN filter is used to convolution the image to obtain the background image, at the same time, the difference between the background image and the original image is obtained. The experimental results show that the background modeling effect of infrared image is evaluated by Mean Squared Error (MSE), Structural Similarity (SSIM) and local Signal-to-noise Ratio Gain (GSNR). Compared with the traditional filtering algorithm, the improved SUSAN filter has achieved better background modeling effect, which can effectively preserve the edge information in the image, and the dim small target is effectively enhanced in the difference graph, which greatly reduces the false alarm rate of the image.

Complex background suppression using global-local registration strategy for the detection of small-moving target on moving platform

NASA Astrophysics Data System (ADS)

Zou, Tianhao; Zuo, Zhengrong

2018-02-01

Target detection is a very important and basic problem of computer vision and image processing. The most often case we meet in real world is a detection task for a moving-small target on moving platform. The commonly used methods, such as Registration-based suppression, can hardly achieve a desired result. To crack this hard nut, we introduce a Global-local registration based suppression method. Differ from the traditional ones, the proposed Global-local Registration Strategy consider both the global consistency and the local diversity of the background, obtain a better performance than normal background suppression methods. In this paper, we first discussed the features about the small-moving target detection on unstable platform. Then we introduced a new strategy and conducted an experiment to confirm its noisy stability. In the end, we confirmed the background suppression method based on global-local registration strategy has a better perform in moving target detection on moving platform.

Robust Measurement via A Fused Latent and Graphical Item Response Theory Model.

PubMed

Chen, Yunxiao; Li, Xiaoou; Liu, Jingchen; Ying, Zhiliang

2018-03-12

Item response theory (IRT) plays an important role in psychological and educational measurement. Unlike the classical testing theory, IRT models aggregate the item level information, yielding more accurate measurements. Most IRT models assume local independence, an assumption not likely to be satisfied in practice, especially when the number of items is large. Results in the literature and simulation studies in this paper reveal that misspecifying the local independence assumption may result in inaccurate measurements and differential item functioning. To provide more robust measurements, we propose an integrated approach by adding a graphical component to a multidimensional IRT model that can offset the effect of unknown local dependence. The new model contains a confirmatory latent variable component, which measures the targeted latent traits, and a graphical component, which captures the local dependence. An efficient proximal algorithm is proposed for the parameter estimation and structure learning of the local dependence. This approach can substantially improve the measurement, given no prior information on the local dependence structure. The model can be applied to measure both a unidimensional latent trait and multidimensional latent traits.

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacFadden, Derek; Zhang Beibei; Brock, Kristy K.

Purpose: Increasing the magnetic resonance imaging (MRI) field strength can improve image resolution and quality, but concerns remain regarding the influence on geometric fidelity. The objectives of the present study were to spatially investigate the effect of 3-Tesla (3T) MRI on clinical target localization for stereotactic radiosurgery. Methods and Materials: A total of 39 patients were enrolled in a research ethics board-approved prospective clinical trial. Imaging (1.5T and 3T MRI and computed tomography) was performed after stereotactic frame placement. Stereotactic target localization at 1.5T vs. 3T was retrospectively analyzed in a representative cohort of patients with tumor (n = 4)more » and functional (n = 5) radiosurgical targets. The spatial congruency of the tumor gross target volumes was determined by the mean discrepancy between the average gross target volume surfaces at 1.5T and 3T. Reproducibility was assessed by the displacement from an averaged surface and volume congruency. Spatial congruency and the reproducibility of functional radiosurgical targets was determined by comparing the mean and standard deviation of the isocenter coordinates. Results: Overall, the mean absolute discrepancy across all patients was 0.67 mm (95% confidence interval, 0.51-0.83), significantly <1 mm (p < .010). No differences were found in the overall interuser target volume congruence (mean, 84% for 1.5T vs. 84% for 3T, p > .4), and the gross target volume surface mean displacements were similar within and between users. The overall average isocenter coordinate discrepancy for the functional targets at 1.5T and 3T was 0.33 mm (95% confidence interval, 0.20-0.48), with no patient-specific differences between the mean values (p >.2) or standard deviations (p >.1). Conclusion: Our results have provided clinically relevant evidence supporting the spatial validity of 3T MRI for use in stereotactic radiosurgery under the imaging conditions used.« less

An Evaluation of the Effectiveness of Intervention in Families with Children with Behavioural Problems within the Context of a Sure Start Programme

ERIC Educational Resources Information Center

Brown, Eleanor A.; Dillenburger, Karola

2004-01-01

Sure Start is a Government project that aims to prevent social exclusion by targeting children between 0 and 4 years of age living in areas of social and economic deprivation. This study examined whether a Tier 2 Behaviour Support Service within a local Sure Start project was able to bring about improvements in children's behaviour and the levels…

Adaptive/nonadaptive proton radiation planning and outcomes in a phase II trial for locally advanced non-small cell lung cancer.

PubMed

Koay, Eugene J; Lege, David; Mohan, Radhe; Komaki, Ritsuko; Cox, James D; Chang, Joe Y

2012-12-01

To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm(3) adaptive and 86.4 cm(3) nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V(70), 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans. Copyright © 2012 Elsevier Inc. All rights reserved.

Template-based modeling and ab initio refinement of protein oligomer structures using GALAXY in CAPRI round 30.

PubMed

Lee, Hasup; Baek, Minkyung; Lee, Gyu Rie; Park, Sangwoo; Seok, Chaok

2017-03-01

Many proteins function as homo- or hetero-oligomers; therefore, attempts to understand and regulate protein functions require knowledge of protein oligomer structures. The number of available experimental protein structures is increasing, and oligomer structures can be predicted using the experimental structures of related proteins as templates. However, template-based models may have errors due to sequence differences between the target and template proteins, which can lead to functional differences. Such structural differences may be predicted by loop modeling of local regions or refinement of the overall structure. In CAPRI (Critical Assessment of PRotein Interactions) round 30, we used recently developed features of the GALAXY protein modeling package, including template-based structure prediction, loop modeling, model refinement, and protein-protein docking to predict protein complex structures from amino acid sequences. Out of the 25 CAPRI targets, medium and acceptable quality models were obtained for 14 and 1 target(s), respectively, for which proper oligomer or monomer templates could be detected. Symmetric interface loop modeling on oligomer model structures successfully improved model quality, while loop modeling on monomer model structures failed. Overall refinement of the predicted oligomer structures consistently improved the model quality, in particular in interface contacts. Proteins 2017; 85:399-407. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

PubMed Central

Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

2017-01-01

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors.

PubMed

Tosi, Umberto; Marnell, Christopher S; Chang, Raymond; Cho, William C; Ting, Richard; Maachani, Uday B; Souweidane, Mark M

2017-02-08

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a "wait-and-see" approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Recent advances in multidisciplinary management of hepatocellular carcinoma

PubMed Central

Gomaa, Asmaa I; Waked, Imam

2015-01-01

The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies.

PubMed

Mangraviti, Antonella; Gullotti, David; Tyler, Betty; Brem, Henry

2016-10-28

Despite recent technological advancements and promising preclinical experiments, brain tumor patients are still met with limited treatment options. Some of the barriers to clinical improvements include the systemic toxicity of cytotoxic compounds, the impedance of the blood brain barrier (BBB), and the lack of therapeutic agents that can selectively target the intracranial tumor environment. To overcome such barriers, a number of chemotherapeutic agents and nucleic acid-based therapies are rapidly being synthesized and tested as new brain tumor-targeted delivery strategies. Novel carriers include liposomal and polymeric nanoparticles, wafers, microchips, microparticle-based nanoplatforms and cells-based vectors. Strong preclinical results suggest that these nanotechnologies are set to transform the therapeutic paradigm for brain tumor treatment. In addition to new tumoricidal agents, parallel work is also being conducted on the BBB front. Preclinical testing of chemical and physical modulation strategies is yielding improved intracranial concentrations. New diagnostic and therapeutic imaging techniques, such as high-intensity focused ultrasound and MRI-guided focused ultrasound, are being used to modulate the BBB in a more precise and non-invasive manner. This review details some of the tremendous advances that are being explored in current brain tumor targeted therapies, including local implant development, nanobiotechnology-based delivery strategies, and techniques of BBB manipulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Formative research for a healthy diet intervention among inner-city adolescents: the importance of family, school and neighborhood environment.

PubMed

Dodson, Jennifer L; Hsiao, Ya-Chun; Kasat-Shors, Madhuri; Murray, Laura; Nguyen, Nga Kim; Richards, Adam K; Gittelsohn, Joel

2009-01-01

To understand influences on diet among low-income African-American adolescents in East Baltimore. Formative research was conducted for a food store-centered healthy diet intervention targeted to inner-city youth. Family, school and neighborhood influences on eating habits and health concepts were explored. Family structure, economic resources and past experiences influence what food means to adolescents. Healthy food in school and local stores is limited. Terminology to categorize foods was identified, including the term "home foods". Suggested adolescent nutritional interventions include promotion of home-based eating, improving availability of healthy foods in school and neighborhood stores, and targeted educational materials.

Noninvasive and Targeted Drug Delivery to the Brain Using Focused Ultrasound

PubMed Central

2013-01-01

Brain diseases are notoriously difficult to treat due to the presence of the blood-brain barrier (BBB). Here, we review the development of focused ultrasound (FUS) as a noninvasive method for BBB disruption, aiding in drug delivery to the brain. FUS can be applied through the skull to a targeted region in the brain. When combined with microbubbles, FUS causes localized and reversible disruption of the BBB. The cellular mechanisms of BBB disruption are presented. Several therapeutic agents have been delivered to the brain resulting in significant improvements in pathology in models of glioblastoma and Alzheimer’s disease. The requirements for clinical translation of FUS will be discussed. PMID:23379618

Improving Suicide Prevention in Dutch Regions by Creating Local Suicide Prevention Action Networks (SUPRANET): A Study Protocol.

PubMed

Gilissen, Renske; De Beurs, Derek; Mokkenstorm, Jan; Mérelle, Saskia; Donker, Gé; Terpstra, Sanne; Derijck, Carla; Franx, Gerdien

2017-03-28

The European Alliance against Depression (EAAD) program is to be introduced in The Netherlands from 2017 onwards. This program to combat suicide consists of interventions on four levels: (1) increasing the awareness of suicide by local media campaigns; (2) training local gatekeepers, such as teachers or police officers; (3) targeting high-risk persons in the community; and (4) training and support of professionals in primary care settings. The implementation starts in seven Dutch pilot regions. Each region is designated as a Suicide Prevention Action NETwork (SUPRANET). This paper describes the SUPRANET program components and the evaluation of its feasibility and impact. The findings will be used to facilitate the national implementation of EAAD in The Netherlands and to add new findings to the existing literature on EAAD.

Improving Suicide Prevention in Dutch Regions by Creating Local Suicide Prevention Action Networks (SUPRANET): A Study Protocol

PubMed Central

Gilissen, Renske; De Beurs, Derek; Mokkenstorm, Jan; Mérelle, Saskia; Donker, Gé; Terpstra, Sanne; Derijck, Carla; Franx, Gerdien

2017-01-01

The European Alliance against Depression (EAAD) program is to be introduced in The Netherlands from 2017 onwards. This program to combat suicide consists of interventions on four levels: (1) increasing the awareness of suicide by local media campaigns; (2) training local gatekeepers, such as teachers or police officers; (3) targeting high-risk persons in the community; and (4) training and support of professionals in primary care settings. The implementation starts in seven Dutch pilot regions. Each region is designated as a Suicide Prevention Action NETwork (SUPRANET). This paper describes the SUPRANET program components and the evaluation of its feasibility and impact. The findings will be used to facilitate the national implementation of EAAD in The Netherlands and to add new findings to the existing literature on EAAD. PMID:28350367

LOCALIZER: subcellular localization prediction of both plant and effector proteins in the plant cell

PubMed Central

Sperschneider, Jana; Catanzariti, Ann-Maree; DeBoer, Kathleen; Petre, Benjamin; Gardiner, Donald M.; Singh, Karam B.; Dodds, Peter N.; Taylor, Jennifer M.

2017-01-01

Pathogens secrete effector proteins and many operate inside plant cells to enable infection. Some effectors have been found to enter subcellular compartments by mimicking host targeting sequences. Although many computational methods exist to predict plant protein subcellular localization, they perform poorly for effectors. We introduce LOCALIZER for predicting plant and effector protein localization to chloroplasts, mitochondria, and nuclei. LOCALIZER shows greater prediction accuracy for chloroplast and mitochondrial targeting compared to other methods for 652 plant proteins. For 107 eukaryotic effectors, LOCALIZER outperforms other methods and predicts a previously unrecognized chloroplast transit peptide for the ToxA effector, which we show translocates into tobacco chloroplasts. Secretome-wide predictions and confocal microscopy reveal that rust fungi might have evolved multiple effectors that target chloroplasts or nuclei. LOCALIZER is the first method for predicting effector localisation in plants and is a valuable tool for prioritizing effector candidates for functional investigations. LOCALIZER is available at http://localizer.csiro.au/. PMID:28300209

Global and local processing near the left and right hands

PubMed Central

Langerak, Robin M.; La Mantia, Carina L.; Brown, Liana E.

2013-01-01

Visual targets can be processed more quickly and reliably when a hand is placed near the target. Both unimodal and bimodal representations of hands are largely lateralized to the contralateral hemisphere, and since each hemisphere demonstrates specialized cognitive processing, it is possible that targets appearing near the left hand may be processed differently than targets appearing near the right hand. The purpose of this study was to determine whether visual processing near the left and right hands interacts with hemispheric specialization. We presented hierarchical-letter stimuli (e.g., small characters used as local elements to compose large characters at the global level) near the left or right hands separately and instructed participants to discriminate the presence of target letters (X and O) from non-target letters (T and U) at either the global or local levels as quickly as possible. Targets appeared at either the global or local level of the display, at both levels, or were absent from the display; participants made foot-press responses. When discriminating target presence at the global level, participants responded more quickly to stimuli presented near the left hand than near either the right hand or in the no-hand condition. Hand presence did not influence target discrimination at the local level. Our interpretation is that left-hand presence may help participants discriminate global information, a right hemisphere (RH) process, and that the left hand may influence visual processing in a way that is distinct from the right hand. PMID:24194725

CNNs flag recognition preprocessing scheme based on gray scale stretching and local binary pattern

NASA Astrophysics Data System (ADS)

Gong, Qian; Qu, Zhiyi; Hao, Kun

2017-07-01

Flag is a rather special recognition target in image recognition because of its non-rigid features with the location, scale and rotation characteristics. The location change can be handled well by the depth learning algorithm Convolutional Neural Networks (CNNs), but the scale and rotation changes are quite a challenge for CNNs. Since it has good rotation and gray scale invariance, the local binary pattern (LBP) is combined with grayscale stretching and CNNs to make LBP and grayscale stretching as CNNs pretreatment, which can not only significantly improve the efficiency of flag recognition, but can also evaluate the recognition effect through ROC, accuracy, MSE and quality factor.

Blocking the mineralocorticoid receptor improves effectiveness of steroid treatment for low back pain in rats

PubMed Central

Ye, Ling; Xie, Wenrui; Strong, Judith A.; Zhang, Jun-Ming

2014-01-01

Background Localized inflammation of lumbar dorsal root ganglia (DRG) may contribute to low back pain. Local injections of corticosteroids used for low back pain are sometimes ineffective. Many corticosteroids activate not only the target glucocorticoid receptor (GR) but also the mineralocorticoid receptor (MR), which may have pro-inflammatory effects countering the effects of GR activation. Methods A low back pain model was implemented in rats (n = 6 -10 per group) by locally inflaming the L5 DRG. Sensory neuron excitability and mechanical hypersensitivity of the hind paws were measured. Tested steroids were applied locally to the inflamed DRG or orally. Results The selective MR blocker eplerenone reduced pain behaviors when given orally starting at the time of surgery, or starting 7 days later. The highly GR-selective agonist fluticasone, applied locally to the inflamed DRG, was much more effective in reducing mechanical hypersensitivity. The MR/GR agonist 6-α methylprednisolone, commonly injected for low back pain, reduced mechanical hypersensitivity when applied locally to the DRG, but was less effective than fluticasone. Its effectiveness was improved by combining it with local eplerenone. All tested steroids reduced hyperexcitability of myelinated sensory neurons (n = 71 – 220 cells per group) after inflammation, particularly abnormal spontaneous activity. Conclusions This preclinical study indicates the MR may play an important role in low back pain involving inflammation. Some MR effects may occur at the level of the sensory neuron. It may be useful to consider the action of clinically used steroids at the MR as well as at the GR. PMID:24781496

Evaluation of a campaign to improve immunization in a rural headstart program.

PubMed

Mayer, J P; Housemann, R; Piepenbrok, B

1999-02-01

This study evaluated an intervention to improve immunization rates in a high poverty, medically underserved rural area employing a pretest-posttest design. The intervention expanded immunization availability, established walk-in appointment policies, and introduced intensified parent education. Formative evaluation indicated specific messages with high salience to parents. As a result, the susceptibility and severity of childhood infectious disease, the outcome efficacy of vaccines, and methods to reduce barriers to immunization were emphasized in communications with parents. Data on DTP1-4, OPV1-3, and MMR were obtained from preschools, local health departments and private medical practices before (n = 567) and after the intervention (n = 331). Following adjustment for birth order and demographics, at post-intervention a significantly greater proportion of children received 6 of 8 vaccines on time. Effect sizes were large. For example, post MMR rates were at least 2X greater than pre rates. Time-series analysis of trend data on local newspaper coverage of child health topics suggested history was not a major threat to the internal validity of this pre-post only design. The findings indicate that comprehensive intervention, targeting improvements in the availability of pediatric care, health system policies and parent behavior, can improve immunization.

Dynamic sound localization in cats

PubMed Central

Ruhland, Janet L.; Jones, Amy E.

2015-01-01

Sound localization in cats and humans relies on head-centered acoustic cues. Studies have shown that humans are able to localize sounds during rapid head movements that are directed toward the target or other objects of interest. We studied whether cats are able to utilize similar dynamic acoustic cues to localize acoustic targets delivered during rapid eye-head gaze shifts. We trained cats with visual-auditory two-step tasks in which we presented a brief sound burst during saccadic eye-head gaze shifts toward a prior visual target. No consistent or significant differences in accuracy or precision were found between this dynamic task (2-step saccade) and the comparable static task (single saccade when the head is stable) in either horizontal or vertical direction. Cats appear to be able to process dynamic auditory cues and execute complex motor adjustments to accurately localize auditory targets during rapid eye-head gaze shifts. PMID:26063772

Mitochondrial Targets for Pharmacological Intervention in Human Disease

PubMed Central

2015-01-01

Over the past several years, mitochondrial dysfunction has been linked to an increasing number of human illnesses, making mitochondrial proteins (MPs) an ever more appealing target for therapeutic intervention. With 20% of the mitochondrial proteome (312 of an estimated 1500 MPs) having known interactions with small molecules, MPs appear to be highly targetable. Yet, despite these targeted proteins functioning in a range of biological processes (including induction of apoptosis, calcium homeostasis, and metabolism), very few of the compounds targeting MPs find clinical use. Recent work has greatly expanded the number of proteins known to localize to the mitochondria and has generated a considerable increase in MP 3D structures available in public databases, allowing experimental screening and in silico prediction of mitochondrial drug targets on an unprecedented scale. Here, we summarize the current literature on clinically active drugs that target MPs, with a focus on how existing drug targets are distributed across biochemical pathways and organelle substructures. Also, we examine current strategies for mitochondrial drug discovery, focusing on genetic, proteomic, and chemogenomic assays, and relevant model systems. As cell models and screening techniques improve, MPs appear poised to emerge as relevant targets for a wide range of complex human diseases, an eventuality that can be expedited through systematic analysis of MP function. PMID:25367773

Global health and social responsibility: a pilot project of the Medical University of Vienna in eastern Ethiopia.

PubMed

Lagler, Heimo; Vargha, Regina; Wagner, Oswald; Seidler, Horst; Ramharter, Michael

2010-02-01

The Medical University of Vienna and the eastern Ethiopian town of Gedamaytu have established a development collaboration with the aim of improving healthcare for the local population. A health survey of the study region was conducted by the university in February 2009 with the purpose of assessing the burden and spectrum of disease, and to evaluate the potential for improvement of healthcare and plan for future targeted health interventions. The most prevalent diseases in pediatric patients were found to be disorders of the respiratory system, febrile conditions and diarrhea. Adult patients suffered most frequently from disorders of the respiratory system, chronic pain, gastric discomfort and febrile conditions. De-worming was offered to all patients in the course of the survey. The anthropometric evaluation of patient data showed a high rate of growth retardation in children below the age of 5 years. Based on these data and on interviews with the local healthcare personnel, healthcare programs and interventions are discussed with the aim of further improving healthcare provision for the population of Gedamaytu.

Longitudinal assessment of hydropeaking impacts on various scales for an improved process understanding and the design of mitigation measures.

PubMed

Hauer, C; Holzapfel, P; Leitner, P; Graf, W

2017-01-01

Hydropeaking is one of the main pressures on the aquatic ecology in alpine rivers. Beside studies on abiotic process and biotic response on the local scale there is a lack in process understanding on the reach scale. Especially longitudinal changes of hydropeaking impacts based on retention processes have not been studied yet. Thus, based on unsteady one-dimensional and two-dimensional depth averaged modelling it was targeted to investigate possible changes in vertical ramping velocity for the discussion of possible mitigation measures at the local scale. Here, we compared artificial and natural sheltering habitats in terms of peak flow. Additionally, the hydropeaking assessment on various river scales was supported by an evaluation of tributaries in an alpine river system. Based on the modelling results and the discussion of the impact assessment of hydropeaking in different case studies we state, that on the first 5km downstream of the turbine outlet a significant decrease in vertical ramping velocity occurs. In this reach, habitat improvements should focus on increasing retention processes considering the higher risk of stranding for juvenile fish and macroinvertebrates. For morphological mitigation measures at the local scale, it turned out that self-formed, near-natural morphology should be targeted in terms of mitigation measure design compared to artificial sheltering habitats. Abundance and biomass of macroinvertebrates are directly linked to substrate variability in self-formed sheltering habitats downstream of gravel bars. Moreover, we ascertained that tributaries are able to contribute to the 'ecological potential' in multi-stressed hydropeaking rivers by providing spawning and rearing habitats for fish. However, for a sustainable improvement of the aquatic environment on all relevant scales, both sediment and flood dynamics have to be considered as important drivers to establish self-formed sheltering habitats in terms of hydropeaking. Copyright © 2016. Published by Elsevier B.V.

Network-targeted cerebellar transcranial magnetic stimulation improves attentional control

PubMed Central

Esterman, Michael; Thai, Michelle; Okabe, Hidefusa; DeGutis, Joseph; Saad, Elyana; Laganiere, Simon E.; Halko, Mark A.

2018-01-01

Developing non-invasive brain stimulation interventions to improve attentional control is extremely relevant to a variety of neurologic and psychiatric populations, yet few studies have identified reliable biomarkers that can be readily modified to improve attentional control. One potential biomarker of attention is functional connectivity in the core cortical network supporting attention - the dorsal attention network (DAN). We used a network-targeted cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance cortical functional connectivity in the DAN. Specifically, in healthy young adults we administered intermittent theta burst TMS (iTBS) to the midline cerebellar node of the DAN and, as a control, the right cerebellar node of the default mode network (DMN). These cerebellar targets were localized using individual resting-state fMRI scans. Participants completed assessments of both sustained (gradual onset continuous performance task, gradCPT) and transient attentional control (attentional blink) immediately before and after stimulation, in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation, participants had significantly fewer attentional lapses (lower commission error rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not affect gradCPT performance. Further, in the DAN condition, individuals with worse baseline gradCPT performance showed the greatest enhancement in gradCPT performance. These results suggest that temporarily increasing functional connectivity in the DAN via network-targeted cerebellar stimulation can enhance sustained attention, particularly in those with poor baseline performance. With regard to transient attention, TMS stimulation improved attentional blink performance across both stimulation sites, suggesting increasing functional connectivity in both networks can enhance this aspect of attention. These findings have important implications for intervention applications of TMS and theoretical models of functional connectivity. PMID:28495634

Nanoprobe-Enhanced, Split Aptamer-Based Electrochemical Sandwich Assay for Ultrasensitive Detection of Small Molecules.

PubMed

Zhao, Tao; Liu, Ran; Ding, Xiaofan; Zhao, Juncai; Yu, Haixiang; Wang, Lei; Xu, Qing; Wang, Xuan; Lou, Xinhui; He, Miao; Xiao, Yi

2015-08-04

It is quite challenging to improve the binding affinity of antismall molecule aptamers. We report that the binding affinity of anticocaine split aptamer pairs improved by up to 66-fold by gold nanoparticles (AuNP)-attached aptamers due to the substantially increased local concentration of aptamers and multiple and simultaneous ligand interactions. The significantly improved binding affinity enables the detection of small molecule targets with unprecedented sensitivity, as demonstrated in nanoprobe-enhanced split aptamer-based electrochemical sandwich assays (NE-SAESA). NE-SAESA replaces the traditional molecular reporter probe with AuNPs conjugated to multiple reporter probes. The increased binding affinity allowed us to use 1,000-fold lower reporter probe concentrations relative to those employed in SAESA. We show that the near-elimination of background in NE-SAESA effectively improves assay sensitivity by ∼1,000-100,000-fold for ATP and cocaine detection, relative to equivalent SAESA. With the ongoing development of new strategies for the selection of aptamers, we anticipate that our sensor platform should offer a generalizable approach for the high-sensitivity detection of diverse targets. More importantly, we believe that NE-SAESA represents a novel strategy to improve the binding affinity between a small molecule and its aptamer and potentially can be extended to other detection platforms.

Stereotactic radiotherapy following surgery for brain metastasis: Predictive factors for local control and radionecrosis.

PubMed

Doré, M; Martin, S; Delpon, G; Clément, K; Campion, L; Thillays, F

2017-02-01

To evaluate local control and adverse effects after postoperative hypofractionated stereotactic radiosurgery in patients with brain metastasis. We reviewed patients who had hypofractionated stereotactic radiosurgery (7.7Gy×3 prescribed to the 70% isodose line, with 2mm planning target volume margin) following resection from March 2008 to January 2014. The primary endpoint was local failure defined as recurrence within the surgical cavity. Secondary endpoints were distant failure rates and the occurrence of radionecrosis. Out of 95 patients, 39.2% had metastatic lesions from a non-small cell lung cancer primary tumour. The median Graded Prognostic Assessment score was 3 (48% of patients). One-year local control rates were 84%. Factors associated with improved local control were no cavity enhancement on pre-radiation MRI (P<0.00001), planning target volume less than 12cm 3 (P=0.005), Graded Prognostic Assessment score 2 or above (P=0.009). One-year distant cerebral control rates were 56%. Thirty-three percent of patients received whole brain radiation therapy. Histologically proven radionecrosis of brain tissue occurred in 7.2% of cases. The size of the preoperative lesion and the volume of healthy brain tissue receiving 21Gy (V 21 ) were both predictive of the incidence of radionecrosis (P=0.010 and 0.036, respectively). Adjuvant hypofractionated stereotactic radiosurgery to the postoperative cavity in patients with brain metastases results in excellent local control in selected patients, helps delay the use of whole brain radiation, and is associated with a relatively low risk of radionecrosis. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Onboard Robust Visual Tracking for UAVs Using a Reliable Global-Local Object Model

PubMed Central

Fu, Changhong; Duan, Ran; Kircali, Dogan; Kayacan, Erdal

2016-01-01

In this paper, we present a novel onboard robust visual algorithm for long-term arbitrary 2D and 3D object tracking using a reliable global-local object model for unmanned aerial vehicle (UAV) applications, e.g., autonomous tracking and chasing a moving target. The first main approach in this novel algorithm is the use of a global matching and local tracking approach. In other words, the algorithm initially finds feature correspondences in a way that an improved binary descriptor is developed for global feature matching and an iterative Lucas–Kanade optical flow algorithm is employed for local feature tracking. The second main module is the use of an efficient local geometric filter (LGF), which handles outlier feature correspondences based on a new forward-backward pairwise dissimilarity measure, thereby maintaining pairwise geometric consistency. In the proposed LGF module, a hierarchical agglomerative clustering, i.e., bottom-up aggregation, is applied using an effective single-link method. The third proposed module is a heuristic local outlier factor (to the best of our knowledge, it is utilized for the first time to deal with outlier features in a visual tracking application), which further maximizes the representation of the target object in which we formulate outlier feature detection as a binary classification problem with the output features of the LGF module. Extensive UAV flight experiments show that the proposed visual tracker achieves real-time frame rates of more than thirty-five frames per second on an i7 processor with 640 × 512 image resolution and outperforms the most popular state-of-the-art trackers favorably in terms of robustness, efficiency and accuracy. PMID:27589769

New horizons in local anesthesia.

PubMed

Lackey, A D

1998-08-01

The computer-controlled local anesthesia system and the TEA system present 21st-century alternatives to the traditional syringe. The TEA system is a non-invasive form of anesthesia that blocks pain electronically, using the same cellular mechanism as local chemical anesthesia. Targeted electronic anesthesia provides pain control for restorative dental procedures without the use of needles or postoperative discomfort, numbness, and swelling. The computer-assisted system outperforms syringes for traditional injections. This new system generates a precisely controlled anesthetic flow rate that eliminates the need for the operator to use thumb pressure to administer the injection. The lightweight pen-grasp handle results in greater tactile feedback, precision, operator ease, and patient comfort. The greatest advantage may be in the new techniques that it makes available. With these techniques, a dentist can target the teeth to achieve profound pulpal anesthesia, often without the annoying side effects of facial numbness. With this new advanced system in the maxillary arch, the AMSA injection offers clinical advantages over traditional anesthesia techniques, according to Dr. Mark Friedman, whom I consulted with earlier this year. In the mandibular arch, a safe and predictable PDL injection technique may replace the need for an inferior alveolar block in numerous clinical situations. The use of these modified injection techniques can have a positive influence on patient safety, patient comfort, and office productivity. Both of these systems take the fear and anxiety out of dental injections. They offer exciting advanced technology for local pain control. Significantly, if patient stress and anxiety are reduced, the operator immediately benefits. New horizons in local anesthesia offer improved opportunities for patient comfort using computer-controlled local anesthetic systems and TEA.

Real time tracking by LOPF algorithm with mixture model

NASA Astrophysics Data System (ADS)

Meng, Bo; Zhu, Ming; Han, Guangliang; Wu, Zhiguo

2007-11-01

A new particle filter-the Local Optimum Particle Filter (LOPF) algorithm is presented for tracking object accurately and steadily in visual sequences in real time which is a challenge task in computer vision field. In order to using the particles efficiently, we first use Sobel algorithm to extract the profile of the object. Then, we employ a new Local Optimum algorithm to auto-initialize some certain number of particles from these edge points as centre of the particles. The main advantage we do this in stead of selecting particles randomly in conventional particle filter is that we can pay more attentions on these more important optimum candidates and reduce the unnecessary calculation on those negligible ones, in addition we can overcome the conventional degeneracy phenomenon in a way and decrease the computational costs. Otherwise, the threshold is a key factor that affecting the results very much. So here we adapt an adaptive threshold choosing method to get the optimal Sobel result. The dissimilarities between the target model and the target candidates are expressed by a metric derived from the Bhattacharyya coefficient. Here, we use both the counter cue to select the particles and the color cur to describe the targets as the mixture target model. The effectiveness of our scheme is demonstrated by real visual tracking experiments. Results from simulations and experiments with real video data show the improved performance of the proposed algorithm when compared with that of the standard particle filter. The superior performance is evident when the target encountering the occlusion in real video where the standard particle filter usually fails.

Integrated approach to improving local CD uniformity in EUV patterning

NASA Astrophysics Data System (ADS)

Liang, Andrew; Hermans, Jan; Tran, Timothy; Viatkina, Katja; Liang, Chen-Wei; Ward, Brandon; Chuang, Steven; Yu, Jengyi; Harm, Greg; Vandereyken, Jelle; Rio, David; Kubis, Michael; Tan, Samantha; Dusa, Mircea; Singhal, Akhil; van Schravendijk, Bart; Dixit, Girish; Shamma, Nader

2017-03-01

Extreme ultraviolet (EUV) lithography is crucial to enabling technology scaling in pitch and critical dimension (CD). Currently, one of the key challenges of introducing EUV lithography to high volume manufacturing (HVM) is throughput, which requires high source power and high sensitivity chemically amplified photoresists. Important limiters of high sensitivity chemically amplified resists (CAR) are the effects of photon shot noise and resist blur on the number of photons received and of photoacids generated per feature, especially at the pitches required for 7 nm and 5 nm advanced technology nodes. These stochastic effects are reflected in via structures as hole-to-hole CD variation or local CD uniformity (LCDU). Here, we demonstrate a synergy of film stack deposition, EUV lithography, and plasma etch techniques to improve LCDU, which allows the use of high sensitivity resists required for the introduction of EUV HVM. Thus, to improve LCDU to a level required by 5 nm node and beyond, film stack deposition, EUV lithography, and plasma etch processes were combined and co-optimized to enhance LCDU reduction from synergies. Test wafers were created by depositing a pattern transfer stack on a substrate representative of a 5 nm node target layer. The pattern transfer stack consisted of an atomically smooth adhesion layer and two hardmasks and was deposited using the Lam VECTOR PECVD product family. These layers were designed to mitigate hole roughness, absorb out-of-band radiation, and provide additional outlets for etch to improve LCDU and control hole CD. These wafers were then exposed through an ASML NXE3350B EUV scanner using a variety of advanced positive tone EUV CAR. They were finally etched to the target substrate using Lam Flex dielectric etch and Kiyo conductor etch systems. Metrology methodologies to assess dimensional metrics as well as chip performance and defectivity were investigated to enable repeatable patterning process development. Illumination conditions in EUV lithography were optimized to improve normalized image log slope (NILS), which is expected to reduce shot noise related effects. It can be seen that the EUV imaging contrast improvement can further reduce post-develop LCDU from 4.1 nm to 3.9 nm and from 2.8 nm to 2.6 nm. In parallel, etch processes were developed to further reduce LCDU, to control CD, and to transfer these improvements into the final target substrate. We also demonstrate that increasing post-develop CD through dose adjustment can enhance the LCDU reduction from etch. Similar trends were also observed in different pitches down to 40 nm. The solutions demonstrated here are critical to the introduction of EUV lithography in high volume manufacturing. It can be seen that through a synergistic deposition, lithography, and etch optimization, LCDU at a 40 nm pitch can be improved to 1.6 nm (3-sigma) in a target oxide layer and to 1.4 nm (3-sigma) at the photoresist layer.

Enhanced flyby science with onboard computer vision: Tracking and surface feature detection at small bodies

NASA Astrophysics Data System (ADS)

Fuchs, Thomas J.; Thompson, David R.; Bue, Brian D.; Castillo-Rogez, Julie; Chien, Steve A.; Gharibian, Dero; Wagstaff, Kiri L.

2015-10-01

Spacecraft autonomy is crucial to increase the science return of optical remote sensing observations at distant primitive bodies. To date, most small bodies exploration has involved short timescale flybys that execute prescripted data collection sequences. Light time delay means that the spacecraft must operate completely autonomously without direct control from the ground, but in most cases the physical properties and morphologies of prospective targets are unknown before the flyby. Surface features of interest are highly localized, and successful observations must account for geometry and illumination constraints. Under these circumstances onboard computer vision can improve science yield by responding immediately to collected imagery. It can reacquire bad data or identify features of opportunity for additional targeted measurements. We present a comprehensive framework for onboard computer vision for flyby missions at small bodies. We introduce novel algorithms for target tracking, target segmentation, surface feature detection, and anomaly detection. The performance and generalization power are evaluated in detail using expert annotations on data sets from previous encounters with primitive bodies.

Tunable cytotoxic aptamer-drug conjugates for the treatment of prostate cancer.

PubMed

Powell Gray, Bethany; Kelly, Linsley; Ahrens, Douglas P; Barry, Ashley P; Kratschmer, Christina; Levy, Matthew; Sullenger, Bruce A

2018-05-01

Therapies that can eliminate both local and metastatic prostate tumor lesions while sparing normal organ tissue are desperately needed. With the goal of developing an improved drug-targeting strategy, we turned to a new class of targeted anticancer therapeutics: aptamers conjugated to highly toxic chemotherapeutics. Cell selection for aptamers with prostate cancer specificity yielded the E3 aptamer, which internalizes into prostate cancer cells without targeting normal prostate cells. Chemical conjugation of E3 to the drugs monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) yields a potent cytotoxic agent that efficiently kills prostate cancer cells in vitro but does not affect normal prostate epithelial cells. Importantly, the E3 aptamer targets tumors in vivo and treatment with the MMAF-E3 conjugate significantly inhibits prostate cancer growth in mice, demonstrating the in vivo utility of aptamer-drug conjugates. Additionally, we report the use of antidotes to block E3 aptamer-drug conjugate cytotoxicity, providing a safety switch in the unexpected event of normal cell killing in vivo.

Adjuvant therapy for advanced renal cell carcinoma.

PubMed

Meissner, Matthew A; McCormick, Barrett Z; Karam, Jose A; Wood, Christopher G

2018-07-01

Locally advanced, non-metastatic renal cell carcinoma (RCC) is conventionally managed with surgery. However, patients are at a high risk of RCC recurrence and have poor survival outcomes. An effective adjuvant systemic treatment is needed to improve on these outcomes. Targeted molecular and immune-based therapies have been investigated, or are under investigation, but their role in this setting remains unclear. Areas covered: A comprehensive search of PubMed and ClinicalTrials.gov was performed for relevant literature. The following topics pertinent to adjuvant therapy in RCC were evaluated: strategies for patient selection, cytokine-based immunotherapy, vaccine therapy, VEGF and non-VEGF targeted molecular agents, and immune checkpoint inhibitors. Expert commentary: Strong evidence for the incorporation of adjuvant therapy in high-risk RCC is lacking. Multiple targeted molecular therapies have been examined with only one approved for use. Genetic and molecular-based prognostic models are needed to determine who may benefit from adjuvant therapy. Developing adjuvant therapy strategies in the future depends on the results of important ongoing trials with immunotherapy and targeted agents.

SU-G-JeP3-01: A Method to Quantify Lung SBRT Target Localization Accuracy Based On Digitally Reconstructed Fluoroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lafata, K; Ren, L; Cai, J

2016-06-15

Purpose: To develop a methodology based on digitally-reconstructed-fluoroscopy (DRF) to quantitatively assess target localization accuracy of lung SBRT, and to evaluate using both a dynamic digital phantom and a patient dataset. Methods: For each treatment field, a 10-phase DRF is generated based on the planning 4DCT. Each frame is pre-processed with a morphological top-hat filter, and corresponding beam apertures are projected to each detector plane. A template-matching algorithm based on cross-correlation is used to detect the tumor location in each frame. Tumor motion relative beam aperture is extracted in the superior-inferior direction based on each frame’s impulse response to themore » template, and the mean tumor position (MTP) is calculated as the average tumor displacement. The DRF template coordinates are then transferred to the corresponding MV-cine dataset, which is retrospectively filtered as above. The treatment MTP is calculated within each field’s projection space, relative to the DRF-defined template. The field’s localization error is defined as the difference between the DRF-derived-MTP (planning) and the MV-cine-derived-MTP (delivery). A dynamic digital phantom was used to assess the algorithm’s ability to detect intra-fractional changes in patient alignment, by simulating different spatial variations in the MV-cine and calculating the corresponding change in MTP. Inter-and-intra-fractional variation, IGRT accuracy, and filtering effects were investigated on a patient dataset. Results: Phantom results demonstrated a high accuracy in detecting both translational and rotational variation. The lowest localization error of the patient dataset was achieved at each fraction’s first field (mean=0.38mm), with Fx3 demonstrating a particularly strong correlation between intra-fractional motion-caused localization error and treatment progress. Filtering significantly improved tracking visibility in both the DRF and MV-cine images. Conclusion: We have developed and evaluated a methodology to quantify lung SBRT target localization accuracy based on digitally-reconstructed-fluoroscopy. Our approach may be useful in potentially reducing treatment margins to optimize lung SBRT outcomes. R01-184173.« less

Postoperative Radiotherapy for Maxillary Sinus Cancer: Long-Term Outcomes and Toxicities of Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bristol, Ian J.; Ahamad, Anesa; Garden, Adam S.

2007-07-01

Purpose: To determine the effects of three changes in radiotherapy technique on the outcomes for patients irradiated postoperatively for maxillary sinus cancer. Methods and Materials: The data of 146 patients treated between 1969 and 2002 were reviewed. The patients were separated into two groups according to the date of treatment. Group 1 included 90 patients treated before 1991 and Group 2 included 56 patients treated after 1991, when the three changes were implemented. The outcomes were compared between the two groups. Results: No differences were found in the 5-year overall survival, recurrence-free survival, local control, nodal control, or distant metastasismore » rates between the two groups (51% vs. 62%, 51% vs. 57%, 76% vs. 70%, 82% vs. 83%, and 28% vs. 17% for Groups 1 and 2, respectively). The three changes were to increase the portals to cover the base of the skull in patients with perineural invasion, reducing their risk of local recurrence; the addition of elective neck irradiation in patients with squamous or undifferentiated histologic features, improving the nodal control, distant metastasis, and recurrence-free survival rates (64% vs. 93%, 20% vs. 3%, and 45% vs. 67%, respectively; p < 0.05 for all comparisons); and improving the dose distributions within the target volume, reducing the late Grade 3-4 complication rates (34% in Group 1 vs. 8% in Group 2, p = 0.014). Multivariate analysis revealed advancing age, the need for enucleation, and positive margins as independent predictors of worse overall survival. The need for enucleation also predicted for worse local control. Conclusion: The three changes in radiotherapy technique improved the outcomes for select patients as predicted. Despite these changes, little demonstrable overall improvement occurred in local control or survival for these patients and additional work must be done.« less

A computer program to determine the possible daily release window for sky target experiments

NASA Technical Reports Server (NTRS)

Michaud, N. H.

1973-01-01

A computer program is presented which is designed to determine the daily release window for sky target experiments. Factors considered in the program include: (1) target illumination by the sun at release time and during the tracking period; (2) look angle elevation above local horizon from each tracking station to the target; (3) solar depression angle from the local horizon of each tracking station during the experimental period after target release; (4) lunar depression angle from the local horizon of each tracking station during the experimental period after target release; and (5) total sky background brightness as seen from each tracking station while viewing the target. Program output is produced in both graphic and data form. Output data can be plotted for a single calendar month or year. The numerical values used to generate the plots are furnished to permit a more detailed review of the computed daily release windows.

The efficacy of targeted Health Agents education to reduce the duration of untreated psychosis in a rural population

PubMed Central

Padilla, Eduardo; Molina, Juan; Kamis, Danielle; Calvo, Maria; Stratton, Lee; Strejilevich, Sergio; Aleman, Gabriela Gonzalez; Guerrero, Gonzalo; Bourdieu, Mercedes; Conesa, Horacio A.; Escobar, Javier I.; de Erausquin, Gabriel A.

2014-01-01

The duration of untreated psychosis (DUP) is a key determinant in the severity of symptoms in patients with schizophrenia. DUP is a modifiable factor that if reduced can improve patient outcome and treatment response. We sought to decrease DUP in rural Argentina by instituting annual training of local health agents to better identify signs of mental illness and offer earlier intervention. DUP was estimated using Schedules of Clinical Assessment in Neuropsychiatry (SCAN). Ongoing training was correlated with a reduction in DUP. Reducing DUP through better screening can decrease the psychosocial burden of disease and improve the trajectory of psychosis. PMID:25439394

Local application of bacteria improves safety of Salmonella-mediated tumor therapy and retains advantages of systemic infection

PubMed Central

Schauer, Tim; Frahm, Michael; Heise, Ulrike; Zimmermann, Kurt; Erhardt, Marc; Weiss, Siegfried

2017-01-01

Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A. We corroborate improved anti-tumor properties of this strain and investigate to which extent an intra-tumoral (i.t.) route of infection could help improve safety and retain advantages of systemic intravenous (i.v.) application. Our results show that i.t. infection exhibits therapeutic efficacy against CT26 and F1.A11 tumors similar to a systemic route of inoculation. Moreover, i.t. application allows extensive dose titration without compromising tumor colonization. Adverse colonization of healthy organs was generally reduced via i.t. infection and accompanied by less body weight loss of the murine host. Despite local application, adjuvanticity remained, and a CT26-specific CD8+ T cell response was effectively stimulated. Most interestingly, also secondary tumors could be targeted with this strategy, thereby extending the unique tumor targeting ability of Salmonella. The i.t. route of inoculation may reap the benefits of systemic infection and aid in safety assurance while directing potency of an oncolytic vector to where it is most needed, namely the primary tumor. PMID:28637010

Local application of bacteria improves safety of Salmonella -mediated tumor therapy and retains advantages of systemic infection.

PubMed

Kocijancic, Dino; Felgner, Sebastian; Schauer, Tim; Frahm, Michael; Heise, Ulrike; Zimmermann, Kurt; Erhardt, Marc; Weiss, Siegfried

2017-07-25

Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A. We corroborate improved anti-tumor properties of this strain and investigate to which extent an intra-tumoral (i.t.) route of infection could help improve safety and retain advantages of systemic intravenous (i.v.) application. Our results show that i.t. infection exhibits therapeutic efficacy against CT26 and F1.A11 tumors similar to a systemic route of inoculation. Moreover, i.t. application allows extensive dose titration without compromising tumor colonization. Adverse colonization of healthy organs was generally reduced via i.t. infection and accompanied by less body weight loss of the murine host. Despite local application, adjuvanticity remained, and a CT26-specific CD8+ T cell response was effectively stimulated. Most interestingly, also secondary tumors could be targeted with this strategy, thereby extending the unique tumor targeting ability of Salmonella. The i.t. route of inoculation may reap the benefits of systemic infection and aid in safety assurance while directing potency of an oncolytic vector to where it is most needed, namely the primary tumor.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakanaka, Katsuyuki; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Hiraoka, Masahiro

Purpose: To investigate the dosimetric advantage of intensity-modulated radiotherapy (IMRT) for whole ventricles (WV) in patients with a localized intracranial germinoma receiving induction chemotherapy. Methods and Materials: Data from 12 consecutive patients with localized intracranial germinomas who received induction chemotherapy and radiotherapy were used. Four-field coplanar three-dimensional conformal radiotherapy (3D-CRT) and seven-field coplanar IMRT plans were created. In both plans, 24 Gy was prescribed in 12 fractions for the planning target volume (PTV) involving WV and tumor bed. In IMRT planning, optimization was conducted to reduce the doses to the organs at risk (OARs) as much as possible, keeping themore » minimum dose equivalent to that of 3D-CRT. The 3D-CRT and IMRT plans were compared in terms of the dose-volume statistics for target coverage and the OARs. Results: IMRT significantly increased the percentage volume of the PTV receiving 24 Gy compared with 3D-CRT (93.5% vs. 84.8%; p = 0.007), while keeping target homogeneity equivalent to 3D-CRT (p = 0.869). The absolute percentage reduction in the irradiated volume of the normal brain receiving 100%, 75%, 50%, and 25% of 24 Gy ranged from 0.7% to 16.0% in IMRT compared with 3D-CRT (p < 0.001). No significant difference was observed in the volume of the normal brain receiving 10% and 5% of 24 Gy between IMRT and 3D-CRT. Conformation number was significantly improved in IMRT (p < 0.001). For other OARs, the mean dose to the cochlea was reduced significantly in IMRT by 22.3% of 24 Gy compared with 3D-CRT (p < 0.001). Conclusions: Compared with 3D-CRT, IMRT for WV improved the target coverage and reduced the irradiated volume of the normal brain in patients with intracranial germinomas receiving induction chemotherapy. IMRT for WV with induction chemotherapy could reduce the late side effects from cranial irradiation without compromising control of the tumor.« less

A novel educational strategy targeting health care workers in underserved communities in Central America to integrate HIV into primary medical care.

PubMed

Flys, Tamara; González, Rosalba; Sued, Omar; Suarez Conejero, Juana; Kestler, Edgar; Sosa, Nestor; McKenzie-White, Jane; Monzón, Irma Irene; Torres, Carmen-Rosa; Page, Kathleen

2012-01-01

Current educational strategies to integrate HIV care into primary medical care in Central America have traditionally targeted managers or higher-level officials, rather than local health care workers (HCWs). We developed a complementary online and on-site interactive training program to reach local HCWs at the primary care level in underserved communities. The training program targeted physicians, nurses, and community HCWs with limited access to traditional onsite training in Panama, Nicaragua, Dominican Republic, and Guatemala. The curriculum focused on principles of HIV care and health systems using a tutor-supported blended educational approach of an 8-week online component, a weeklong on-site problem-solving workshop, and individualized project-based interventions. Of 258 initially active participants, 225 (225/258=87.2%) successfully completed the online component and the top 200 were invited to the on-site workshop. Of those, 170 (170/200=85%) attended the on-site workshop. In total, 142 completed all three components, including the project phase. Quantitative and qualitative evaluation instruments included knowledge assessments, reflexive essays, and acceptability surveys. The mean pre and post-essay scores demonstrating understanding of social determinants, health system organization, and integration of HIV services were 70% and 87.5%, respectively, with an increase in knowledge of 17.2% (p<0.001). The mean pre- and post-test scores evaluating clinical knowledge were 70.9% and 90.3%, respectively, with an increase in knowledge of 19.4% (p<0.001). A survey of Likert scale and open-ended questions demonstrated overwhelming participant satisfaction with course content, structure, and effectiveness in improving their HIV-related knowledge and skills. This innovative curriculum utilized technology to target HCWs with limited access to educational resources. Participants benefited from technical skills acquired through the process, and could continue working within their underserved communities while participating in the online component and then implement interventions that successfully converted theoretical knowledge to action to improve integration of HIV care into primary care.

Human tracking in thermal images using adaptive particle filters with online random forest learning

NASA Astrophysics Data System (ADS)

Ko, Byoung Chul; Kwak, Joon-Young; Nam, Jae-Yeal

2013-11-01

This paper presents a fast and robust human tracking method to use in a moving long-wave infrared thermal camera under poor illumination with the existence of shadows and cluttered backgrounds. To improve the human tracking performance while minimizing the computation time, this study proposes an online learning of classifiers based on particle filters and combination of a local intensity distribution (LID) with oriented center-symmetric local binary patterns (OCS-LBP). Specifically, we design a real-time random forest (RF), which is the ensemble of decision trees for confidence estimation, and confidences of the RF are converted into a likelihood function of the target state. First, the target model is selected by the user and particles are sampled. Then, RFs are generated using the positive and negative examples with LID and OCS-LBP features by online learning. The learned RF classifiers are used to detect the most likely target position in the subsequent frame in the next stage. Then, the RFs are learned again by means of fast retraining with the tracked object and background appearance in the new frame. The proposed algorithm is successfully applied to various thermal videos as tests and its tracking performance is better than those of other methods.

Influence of aging on human sound localization

PubMed Central

Dobreva, Marina S.; O'Neill, William E.

2011-01-01

Errors in sound localization, associated with age-related changes in peripheral and central auditory function, can pose threats to self and others in a commonly encountered environment such as a busy traffic intersection. This study aimed to quantify the accuracy and precision (repeatability) of free-field human sound localization as a function of advancing age. Head-fixed young, middle-aged, and elderly listeners localized band-passed targets using visually guided manual laser pointing in a darkened room. Targets were presented in the frontal field by a robotically controlled loudspeaker assembly hidden behind a screen. Broadband targets (0.1–20 kHz) activated all auditory spatial channels, whereas low-pass and high-pass targets selectively isolated interaural time and intensity difference cues (ITDs and IIDs) for azimuth and high-frequency spectral cues for elevation. In addition, to assess the upper frequency limit of ITD utilization across age groups more thoroughly, narrowband targets were presented at 250-Hz intervals from 250 Hz up to ∼2 kHz. Young subjects generally showed horizontal overestimation (overshoot) and vertical underestimation (undershoot) of auditory target location, and this effect varied with frequency band. Accuracy and/or precision worsened in older individuals for broadband, high-pass, and low-pass targets, reflective of peripheral but also central auditory aging. In addition, compared with young adults, middle-aged, and elderly listeners showed pronounced horizontal localization deficiencies (imprecision) for narrowband targets within 1,250–1,575 Hz, congruent with age-related central decline in auditory temporal processing. Findings underscore the distinct neural processing of the auditory spatial cues in sound localization and their selective deterioration with advancing age. PMID:21368004

A Novel Method of Localization for Moving Objects with an Alternating Magnetic Field

PubMed Central

Gao, Xiang; Yan, Shenggang; Li, Bin

2017-01-01

Magnetic detection technology has wide applications in the fields of geological exploration, biomedical treatment, wreck removal and localization of unexploded ordinance. A large number of methods have been developed to locate targets with static magnetic fields, however, the relation between the problem of localization of moving objectives with alternating magnetic fields and the localization with a static magnetic field is rarely studied. A novel method of target localization based on coherent demodulation was proposed in this paper. The problem of localization of moving objects with an alternating magnetic field was transformed into the localization with a static magnetic field. The Levenberg-Marquardt (L-M) algorithm was applied to calculate the position of the target with magnetic field data measured by a single three-component magnetic sensor. Theoretical simulation and experimental results demonstrate the effectiveness of the proposed method. PMID:28430153

Proton Radiation Therapy for Head and Neck Cancer: A Review of the Clinical Experience to Date

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holliday, Emma B.; Frank, Steven J., E-mail: sjfrank@mdanderson.org

2014-06-01

Proton beam radiation has been used for cancer treatment since the 1950s, but recent increasing interest in this form of therapy and the construction of hospital-based and clinic-based facilities for its delivery have greatly increased both the number of patients and the variety of tumors being treated with proton therapy. The mass of proton particles and their unique physical properties (ie, the Bragg peak) allow proton therapy to spare normal tissues distal to the tumor target from incidental irradiation. Initial observations show that proton therapy is particularly useful for treating tumors in challenging locations close to nontarget critical structures. Specifically,more » improvements in local control outcomes for patients with chordoma, chonodrosarcoma, and tumors in the sinonasal regions have been reported in series using proton. Improved local control and survival outcomes for patients with cancer of the head and neck region have also been seen with the advent of improvements in better imaging and multimodality therapy comprising surgery, radiation therapy, and chemotherapy. However, aggressive local therapy in the proximity of critical normal structures to tumors in the head and neck region may produce debilitating early and late toxic effects. Great interest has been expressed in evaluating whether proton therapy can improve outcomes, especially early and late toxicity, when used in the treatment of head and neck malignancies. This review summarizes the progress made to date in addressing this question.« less

Can a public health intervention improve awareness and health-seeking behaviour for glaucoma?

PubMed

Baker, H; Murdoch, I E

2008-12-01

To investigate whether a public education campaign can increase awareness and change help-seeking behaviour with respect to ocular health in an Indian population. A health knowledge questionnaire was used investigating and assessing the health campaign. The health campaign comprised four components: (1) television, (2) local press, (3) local radio and (4) places of worship. The target population were Indian residents in Southall, Ealing aged 60+. The aim was to get people to go and have their eyes tested at their local optometric practice. Optometric practices within the borough of Ealing collected sight-test data for the study over 6 months before and after the advertising campaign. The repeat in-depth glaucoma knowledge questionnaire showed a significant increase in the number of people who had heard of glaucoma rising from 22% to 53%. Before intervention, most people had heard about glaucoma from their GP, friend or relative. After intervention, the majority (69%) had heard of glaucoma from the radio. This study has shown a significant increase in awareness from using different kinds of media and has shown radio to be the most effective in our target community. Although the campaign has raised awareness, this study has not shown a change in health-seeking behaviour.

Toll-Like Receptor Signaling in Burn Wound Healing and Scarring

PubMed Central

D'Arpa, Peter; Leung, Kai P.

2017-01-01

Significance: Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) emanate from burn-injured tissue and enter systemic circulation. Locally and systemically, they activate pattern-recognition receptors, including toll-like receptors (TLRs), to stimulate cytokine secretion, which in the severest burns typically results in extreme systemic cytokine levels, a dysfunctioning immune system, infection, impaired healing, and excessive scarring. This system-wide disruption of homeostasis can advance to life-threatening, multiorgan dysfunction syndrome. Knowledge of DAMP- and PAMP-TLR signaling may lead to treatments that ameliorate local and systemic inflammation and reduce scarring and other burn injury sequela. Recent Advances: Many PAMPs and DAMPs, the TLRs they activate, and their downstream signaling molecules have been shown to contribute to local and systemic inflammation and tissue damage following burn injury. Critical Issues: Whether TLR-pathway-targeting treatments applied at different times postburn injury might improve scarring remains an open question. The evaluation of this question requires the use of appropriate preclinical and clinical burn models carried out until after mature scar has formed. Future Directions: After TLR-pathway-targeting treatments are evaluated in porcine burn wound models and their safety is demonstrated, they can be tested in proof-of-concept clinical burn wound models. PMID:29062590

Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy

PubMed Central

Li, Ling; Li, Xia; Wu, Yuzhe; Song, Linjiang; Yang, Xi; He, Tao; Wang, Ning; Yang, Suleixin; Zeng, Yan; Wu, Qinjie; Qian, Zhiyong; Wei, Yuquan; Gong, Changyang

2017-01-01

Cancer stem cell-like cells (CSCL) are responsible for tumor recurrence associated with conventional therapy (e.g. surgery, radiation, and chemotherapy). Here, we developed a novel multifunctional nucleus-targeting nanoparticle-based gene delivery system which is capable of targeting and eradicating CSCL. These nanoparticles can facilitate efficient endosomal escape and spontaneously penetrate into nucleus without additional nuclear localization signal. They also induced extremely high gene transfection efficiency (>95%) even in culture medium containing 30% serum, which significantly surpassed that of some commercial transfection reagents, such as Lipofectamine 2000 and Lipofectamine 3000 etc. Especially, when loaded with the TRAIL gene, this system mediated remarkable depletion of CSCL. Upon systemic administration, the nanoparticles accumulated in tumor sites while sparing the non-cancer tissues and significantly inhibited the growth of tumors with no evident systemic toxicity. Taken together, our results suggest that these novel multifunctional, nucleus-targeting nanoparticles are a very promising in vivo gene delivery system capable of targeting CSCL and represent a new treatment candidate for improving the survival of cancer patients. PMID:28529641

Targeted Delivery of Hyaluronan-Immobilized Magnetic Ceramic Nanocrystals.

PubMed

Wu, Hsi-Chin; Wang, Tzu-Wei; Hsieh, Shun-Yu; Sun, Jui-Sheng; Kang, Pei-Leun

2016-01-01

Effective cancer therapy relies on delivering the therapeutic agent precisely to the target site to improve the treatment outcome and to minimize side effects. Although surgery, chemotherapy, and radiotherapy are the standard methods commonly used in clinics, hyperthermia has been developed as a new and promising strategy for cancer therapy. In this study, magnetic bioceramic hydroxyapatite (mHAP) nanocrystals have been developed as heat mediator for intracellular hyperthermia. Hyaluronic acid (HA) modified mHAP nanocrystals are synthesized by a wet chemical precipitation process to achieve active targeting. The results demonstrate that the HA targeting moiety conjugated by a poly(ethylene glycol) (PEG) spacer arm is successfully immobilized on the surface of mHAP. The HA-modified mHAP possesses relatively good biocompatibility, an adequate biodegradation rate and superparamagnetic properties. The HA-modified mHAP could be localized and internalized into HA receptor-overexpressed malignant cells (e.g., MDA-MB-231 cell) and used as the heat generating agent for intracellular hyperthermia. The results from this study indicate that biocompatible HA-modified mHAP shows promise as a novel heat mediator and a specific targeting nanoagent for intracellular hyperthermia cancer therapy.

Modulation of Memory T Cells to Control Acquired Bone Marrow Failure

DTIC Science & Technology

2016-01-01

Representative images show the tissues from one of 6 recipients in each group at day 7 after transplantation. Images were obtained with an OlympusBX41...alloreactive effector T cells capable of mediating host tissue injury and could be beneficial targets for improving the efficacy of allogeneic HSCT...leukemia (GVL) effect, but showed impaired expansion in local tissues .69-72 This nTEM pool might have less diverse T cell receptor (TCR) repertoire

No psychological effect of color context in a low level vision task

PubMed Central

Pedley, Adam; Wade, Alex R

2013-01-01

Background: A remarkable series of recent papers have shown that colour can influence performance in cognitive tasks. In particular, they suggest that viewing a participant number printed in red ink or other red ancillary stimulus elements improves performance in tasks requiring local processing and impedes performance in tasks requiring global processing whilst the reverse is true for the colour blue. The tasks in these experiments require high level cognitive processing such as analogy solving or remote association tests and the chromatic effect on local vs. global processing is presumed to involve widespread activation of the autonomic nervous system. If this is the case, we might expect to see similar effects on all local vs. global task comparisons. To test this hypothesis, we asked whether chromatic cues also influence performance in tasks involving low level visual feature integration. Methods: Subjects performed either local (contrast detection) or global (form detection) tasks on achromatic dynamic Glass pattern stimuli. Coloured instructions, target frames and fixation points were used to attempt to bias performance to different task types. Based on previous literature, we hypothesised that red cues would improve performance in the (local) contrast detection task but would impede performance in the (global) form detection task.  Results: A two-way, repeated measures, analysis of covariance (2×2 ANCOVA) with gender as a covariate, revealed no influence of colour on either task, F(1,29) = 0.289, p = 0.595, partial η 2 = 0.002. Additional analysis revealed no significant differences in only the first attempts of the tasks or in the improvement in performance between trials. Discussion: We conclude that motivational processes elicited by colour perception do not influence neuronal signal processing in the early visual system, in stark contrast to their putative effects on processing in higher areas. PMID:25075280

No psychological effect of color context in a low level vision task.

PubMed

Pedley, Adam; Wade, Alex R

2013-01-01

A remarkable series of recent papers have shown that colour can influence performance in cognitive tasks. In particular, they suggest that viewing a participant number printed in red ink or other red ancillary stimulus elements improves performance in tasks requiring local processing and impedes performance in tasks requiring global processing whilst the reverse is true for the colour blue. The tasks in these experiments require high level cognitive processing such as analogy solving or remote association tests and the chromatic effect on local vs. global processing is presumed to involve widespread activation of the autonomic nervous system. If this is the case, we might expect to see similar effects on all local vs. global task comparisons. To test this hypothesis, we asked whether chromatic cues also influence performance in tasks involving low level visual feature integration. Subjects performed either local (contrast detection) or global (form detection) tasks on achromatic dynamic Glass pattern stimuli. Coloured instructions, target frames and fixation points were used to attempt to bias performance to different task types. Based on previous literature, we hypothesised that red cues would improve performance in the (local) contrast detection task but would impede performance in the (global) form detection task.  A two-way, repeated measures, analysis of covariance (2×2 ANCOVA) with gender as a covariate, revealed no influence of colour on either task, F(1,29) = 0.289, p = 0.595, partial η (2) = 0.002. Additional analysis revealed no significant differences in only the first attempts of the tasks or in the improvement in performance between trials. We conclude that motivational processes elicited by colour perception do not influence neuronal signal processing in the early visual system, in stark contrast to their putative effects on processing in higher areas.

Optimization of CRISPR/Cas9 genome editing for loss-of-function in the early chick embryo.

PubMed

Gandhi, Shashank; Piacentino, Michael L; Vieceli, Felipe M; Bronner, Marianne E

2017-12-01

The advent of CRISPR/Cas9 has made genome editing possible in virtually any organism, including those not previously amenable to genetic manipulations. Here, we present an optimization of CRISPR/Cas9 for application to early avian embryos with improved efficiency via a three-fold strategy. First, we employed Cas9 protein flanked with two nuclear localization signal sequences for improved nuclear localization. Second, we used a modified guide RNA (gRNA) scaffold that obviates premature termination of transcription and unstable Cas9-gRNA interactions. Third, we used a chick-specific U6 promoter that yields 4-fold higher gRNA expression than the previously utilized human U6. For rapid screening of gRNAs for in vivo applications, we also generated a chicken fibroblast cell line that constitutively expresses Cas9. As proof of principle, we performed electroporation-based loss-of-function studies in the early chick embryo to knock out Pax7 and Sox10, key transcription factors with known functions in neural crest development. The results show that CRISPR/Cas9-mediated deletion causes loss of their respective proteins and transcripts, as well as predicted downstream targets. Taken together, the results reveal the utility of this optimized CRISPR/Cas9 method for targeted gene knockout in chicken embryos in a manner that is reproducible, robust and specific. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuroblastoma: clinical and biological approach to risk stratification and treatment.

PubMed

Tolbert, Vanessa P; Matthay, Katherine K

2018-05-01

Neuroblastoma is the most common extra-cranial solid tumor of childhood and the most common in the first year of life. It is a unique malignancy in that infants often present with either localized or metastatic disease that can spontaneously regress without intervention while older children can succumb to the disease after months to years of arduous therapy. Given this wide range of outcomes, the International Neuroblastoma Risk Group was created to stratify patients based on presenting characteristics and tumor biology in order to guide intensity of treatment strategies. The goal has been to decrease therapy for low-risk patients to avoid long-term complications while augmenting and targeting therapies for high-risk patients to improve overall survival. The international risk stratification depends on age, stage, histology, MYCN gene amplification status, tumor cell ploidy and segmental chromosomal abnormalities. Treatment for asymptomatic low-risk patients with an estimated survival of > 98% is often observation or surgical resection alone, whereas intermediate-risk patients with an estimated survival of > 90% require moderate doses of response-adjusted chemotherapy along with resection. High-risk patients undergo multiple cycles of combination chemotherapy before surgery, followed by consolidation with myeloablative autologous hematopoietic stem cell transplantation and local radiation and finally immunotherapy with differentiation therapy as maintenance phase. With this approach, outcome for patients with neuroblastoma has improved, as the field continues to expand efforts in more targeted therapies for high-risk patients.

Local linear regression for function learning: an analysis based on sample discrepancy.

PubMed

Cervellera, Cristiano; Macciò, Danilo

2014-11-01

Local linear regression models, a kind of nonparametric structures that locally perform a linear estimation of the target function, are analyzed in the context of empirical risk minimization (ERM) for function learning. The analysis is carried out with emphasis on geometric properties of the available data. In particular, the discrepancy of the observation points used both to build the local regression models and compute the empirical risk is considered. This allows to treat indifferently the case in which the samples come from a random external source and the one in which the input space can be freely explored. Both consistency of the ERM procedure and approximating capabilities of the estimator are analyzed, proving conditions to ensure convergence. Since the theoretical analysis shows that the estimation improves as the discrepancy of the observation points becomes smaller, low-discrepancy sequences, a family of sampling methods commonly employed for efficient numerical integration, are also analyzed. Simulation results involving two different examples of function learning are provided.

Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

PubMed

Cha, Eugene K; Eastham, James A

2015-05-01

Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

What can local authorities do to improve the social care-related quality of life of older adults living at home? Evidence from the Adult Social Care Survey.

PubMed

van Leeuwen, K M; Malley, J; Bosmans, J E; Jansen, A P D; Ostelo, R W; van der Horst, H E; Netten, A

2014-09-01

Local authorities spend considerable resources on social care at home for older adults. Given the expected growth in the population of older adults and budget cuts on local government, it is important to find efficient ways of maintaining and improving the quality of life of older adults. The ageing in place literature suggests that policies in other functions of local authorities may have a significant role to play. This study aims to examine the associations between social care-related quality of life (SCRQoL) in older adults and three potential policy targets for local authorities: (i) accessibility of information and advice, (ii) design of the home and (iii) accessibility of the local area. We used cross-sectional data from the English national Adult Social Care Survey (ASCS) 2010/2011 on service users aged 65 years and older and living at home (N=29,935). To examine the association between SCRQoL, as measured by the ASCOT, and three single-item questions about accessibility of information, design of the home and accessibility of the local area, we estimate linear and quantile regression models. After adjusting for physical and mental health factors and other confounders our findings indicate that SCRQoL is significantly lower for older adults who find it more difficult to find information and advice, for those who report that their home design is inappropriate for their needs and for those who find it more difficult to get around their local area. In addition, these three variables are as strongly associated with SCRQoL as physical and mental health factors. We conclude that in seeking to find ways to maintain and improve the quality of life of social care users living at home, local authorities could look more broadly across their responsibilities. Further research is required to explore the cost-effectiveness of these options compared to standard social care services. Copyright © 2014 Elsevier Ltd. All rights reserved.

Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy

PubMed Central

Zhang, Nisi; Yan, Fei; Liang, Xiaolong; Wu, Manxiang; Shen, Yuanyuan; Chen, Min; Xu, Yunxue; Zou, Guangyang; Jiang, Peng; Tang, Caiyun; Zheng, Hairong; Dai, Zhifei

2018-01-01

Rationale: Treatment for Parkinson's disease (PD) is challenged by the presence of the blood-brain barrier (BBB) that significantly limits the effective drug concentration in a patient's brain for therapeutic response throughout various stages of PD. Curcumin holds the potential for α-synuclein clearance to treat PD; however, its applications are still limited due to its low bioavailability and poor permeability through the BBB in a free form. Methods: Herein, this paper fabricated curcumin-loaded polysorbate 80-modified cerasome (CPC) nanoparticles (NPs) with a mean diameter of ~110 nm for enhancing the localized curcumin delivery into the targeted brain nuclei via effective BBB opening in combination with ultrasound-targeted microbubble destruction (UTMD). Results: The liposomal nanohybrid cerasome exhibited superior stability towards PS 80 surfactant solubilization and longer circulation lifetime (t1/2 = 6.22 h), much longer than free curcumin (t1/2 = 0.76 h). The permeation was found to be 1.7-fold higher than that of CPC treatment only at 6 h after the systemic administration of CPC NPs. Notably, motor behaviors, dopamine (DA) level and tyrosine hydroxylase (TH) expression all returned to normal, thanks to α-synuclein (AS) removal mediated by efficient curcumin delivery to the striatum. Most importantly, the animal experiment demonstrated that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice had notably improved behavior disorder and dopamine depletion during two-week post-observation after treatment with CPC NPs (15 mg curcumin/kg) coupled with UTMD. Conclusion: This novel CPC-UTMD formulation approach could be an effective, safe and amenable choice with higher therapeutic relevance and fewer unwanted complications than conventional chemotherapeutics delivery systems for PD treatment in the near future. PMID:29721078

Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

PubMed Central

Zhou, Jiehua; Rossi, John J.

2014-01-01

One hundred years ago, Dr. Paul Ehrlich popularized the “magic bullet” concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, “targeted therapy” that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges. PMID:24936916

Neurostimulation to improve level of consciousness in patients with epilepsy.

PubMed

Gummadavelli, Abhijeet; Kundishora, Adam J; Willie, Jon T; Andrews, John P; Gerrard, Jason L; Spencer, Dennis D; Blumenfeld, Hal

2015-06-01

When drug-resistant epilepsy is poorly localized or surgical resection is contraindicated, current neurostimulation strategies such as deep brain stimulation and vagal nerve stimulation can palliate the frequency or severity of seizures. However, despite medical and neuromodulatory therapy, a significant proportion of patients continue to experience disabling seizures that impair awareness, causing disability and risking injury or sudden unexplained death. We propose a novel strategy in which neuromodulation is used not only to reduce seizures but also to ameliorate impaired consciousness when the patient is in the ictal and postictal states. Improving or preventing alterations in level of consciousness may have an effect on morbidity (e.g., accidents, drownings, falls), risk for death, and quality of life. Recent studies may have elucidated underlying networks and mechanisms of impaired consciousness and yield potential novel targets for neuromodulation. The feasibility, benefits, and pitfalls of potential deep brain stimulation targets are illustrated in human and animal studies involving minimally conscious/vegetative states, movement disorders, depth of anesthesia, sleep-wake regulation, and epilepsy. We review evidence that viable therapeutic targets for impaired consciousness associated with seizures may be provided by key nodes of the consciousness system in the brainstem reticular activating system, hypothalamus, basal ganglia, thalamus, and basal forebrain.

Large-scale systematic analysis of 2D fingerprint methods and parameters to improve virtual screening enrichments.

PubMed

Sastry, Madhavi; Lowrie, Jeffrey F; Dixon, Steven L; Sherman, Woody

2010-05-24

A systematic virtual screening study on 11 pharmaceutically relevant targets has been conducted to investigate the interrelation between 8 two-dimensional (2D) fingerprinting methods, 13 atom-typing schemes, 13 bit scaling rules, and 12 similarity metrics using the new cheminformatics package Canvas. In total, 157 872 virtual screens were performed to assess the ability of each combination of parameters to identify actives in a database screen. In general, fingerprint methods, such as MOLPRINT2D, Radial, and Dendritic that encode information about local environment beyond simple linear paths outperformed other fingerprint methods. Atom-typing schemes with more specific information, such as Daylight, Mol2, and Carhart were generally superior to more generic atom-typing schemes. Enrichment factors across all targets were improved considerably with the best settings, although no single set of parameters performed optimally on all targets. The size of the addressable bit space for the fingerprints was also explored, and it was found to have a substantial impact on enrichments. Small bit spaces, such as 1024, resulted in many collisions and in a significant degradation in enrichments compared to larger bit spaces that avoid collisions.

On FAST3D simulations of directly-driven inertial-fusion targets with high-Z layers for reducing laser imprint and surface non-uniformity growth

NASA Astrophysics Data System (ADS)

Bates, Jason; Schmitt, Andrew; Klapisch, Marcel; Karasik, Max; Obenschain, Steve

2013-10-01

Modifications to the FAST3D code have been made to enhance its ability to simulate the dynamics of plastic ICF targets with high-Z overcoats. This class of problems is challenging computationally due in part to plasma conditions that are not in a state of local thermodynamic equilibrium and to the presence of mixed computational cells containing more than one material. Recently, new opacity tables for gold, palladium and plastic have been generated with an improved version of the STA code. These improved tables provide smoother, higher-fidelity opacity data over a wider range of temperature and density states than before, and contribute to a more accurate treatment of radiative transfer processes in FAST3D simulations. Furthermore, a new, more efficient subroutine known as ``MMEOS'' has been installed in the FAST3D code for determining pressure and temperature equilibrium conditions within cells containing multiple materials. We will discuss these topics, and present new simulation results for high-Z planar-target experiments performed recently on the NIKE Laser Facility. Work supported by DOE/NNSA.

Newly Engineered Magnetic Erythrocytes for Sustained and Targeted Delivery of Anti-Cancer Therapeutic Compounds

PubMed Central

Taranta, Monia; Naldi, Ilaria

2011-01-01

Cytotoxic chemotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can they be selectively improved? Alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. These formulations are associated with problems like severe toxic side effects on healthy organs, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site-specific controlled drug delivery systems. In response to these concerns, we have developed a new drug delivery system based on magnetic erythrocytes engineered with a viral spike fusion protein. This new erythrocyte-based drug delivery system has the potential for magnetic-controlled site-specific localization and highly efficient fusion capability with the targeted cells. Here we show that the erythro-magneto-HA virosomes drug delivery system is able to attach and fuse with the target cells and to efficiently release therapeutic compounds inside the cells. The efficacy of the anti-cancer drug employed is increased and the dose required is 10 time less than that needed with conventional therapy. PMID:21373641

Stereotactic body radiation therapy for isolated hilar and mediastinal non-small cell lung cancers.

PubMed

Horne, Zachary D; Richman, Adam H; Dohopolski, Michael J; Clump, David A; Burton, Steven A; Heron, Dwight E

2018-01-01

The seminal phase II trial for pulmonary stereotactic body radiation therapy (SBRT) suggested that SBRT to central lesions resulted in unacceptable toxicity. Alternative dose-fractionation schemes have been proposed which may improve safety without compromise of efficacy. We report our institutional outcomes of SBRT for hilar/mediastinal non-small cell lung cancer (NSCLC). A retrospective review was conducted of patients with NSCLC in a hilar or mediastinal nodal station which was treated with SBRT. Patients presented with a lesion involving the hilum or mediastinum from primary or oligorecurrent NSCLC. Kaplan-Meier with log-rank testing and Cox analysis were utilized for outcomes analysis. From 2008-2015, 40 patients with median age of 70 were treated with SBRT for primary/oligorecurrent hilar/mediastinal NSCLC with median follow-up of 16.4 months. 85% presented with oligorecurrent disease at a median of 22.4 months following definitive therapy. The aortico-pulmonary window was the target in 40%, the hilum in 25%, lower paratracheal in 20%, subcarinal in 10%, and prevascular in 5%. The median dose was 48Gy in 4 fractions (range: 35-48Gy in 4-5 fractions). Median overall (OS) and progression-free (PFS) survivals were 22.7 and 13.1 months, respectively. Two-year local control was 87.7% and not significantly different between hilar and mediastinal targets. Median PFS was significantly improved in patients with hilar vs mediastinal nodal targets: 33.3 vs 8.4 months, respectively (p=0.031). OS was not statistically different between hilar and mediastinal targets (p=0.359). On multivariable analysis, hilar vs mediastinal target predicted for PFS (HR 3.045 95%CI [1.044-8.833], p=0.042), as did shorter time to presentation in patients with oligorecurrence (HR 0.983 [95%CI 0.967-1.000], p=0.049). Acute grade 3+ morbidity was seen in 3 patients (hemoptysis, pericardial/pleural effusion, heart failure) and late grade 3+ morbidity (hemoptysis) in 1 patient. Hilar/mediastinal SBRT appears to be a safe technique for the local control of isolated nodal disease with limited toxicity from the fractionation schemes utilized. Copyright © 2017 Elsevier B.V. All rights reserved.

Scene analysis for effective visual search in rough three-dimensional-modeling scenes

NASA Astrophysics Data System (ADS)

Wang, Qi; Hu, Xiaopeng

2016-11-01

Visual search is a fundamental technology in the computer vision community. It is difficult to find an object in complex scenes when there exist similar distracters in the background. We propose a target search method in rough three-dimensional-modeling scenes based on a vision salience theory and camera imaging model. We give the definition of salience of objects (or features) and explain the way that salience measurements of objects are calculated. Also, we present one type of search path that guides to the target through salience objects. Along the search path, when the previous objects are localized, the search region of each subsequent object decreases, which is calculated through imaging model and an optimization method. The experimental results indicate that the proposed method is capable of resolving the ambiguities resulting from distracters containing similar visual features with the target, leading to an improvement of search speed by over 50%.

A community-engaged approach to select geographic areas for interventions to reduce health disparities.

PubMed

Cromley, Ellen; Kleinman, Lawrence C; Ramos, Michelle A; Arniella, Guedy; Viswanathan, Nalini; Garel, Mischka; Horowitz, Carol R

2011-01-01

While neighborhood-based approaches to eliminate health disparities are on the rise, there is little guidance on how researchers may engage with community partners to select geographic areas for interventions to reduce health disparities. We aimed to identify a small geographic area to target interventions to improve diabetes-related outcomes. We describe lessons learned from a community-engaged approach to specify the geographic area of focus. A community-academic partnership of more than 20 organizations collaborated to develop and employ a 5-stage process to specify a target area for diabetes preventions and control activities. A coalition with local knowledge and ties to the community can develop criteria and direct a process leading to selection of a geographic area, increased research capacity, and strengthened relationships among partners. A participatory approach can be effective in defining a geographic area for targeting interventions to reduce health disparities.

Local processes in preattentive feature detection.

PubMed

Bacon, W F; Egeth, H E

1991-02-01

Sagi and Julesz (1987) claimed that for a target to be detected preattentively, it must be within some small critical distance of a nontarget. The independent effects of separation and display size, which were confounded in the Sagi and Julesz experiments, were examined. Experiments 1 and 2 revealed that in tasks requiring search for a color-defined target, target-nontarget separation had no effect on reaction time (RT). Display size, however, was inversely related to RT. Experiment 3 ruled out the possibility that the decreasing function of RT with display size was due to arousal caused by higher display luminance. When nontarget grouping was inhibited, (Exp. 4) it was found that RT no longer decreased with increasing display size. This suggests that nontarget grouping may have been the cause of the improved performance at larger display sizes. Experiments 5 and 6 extended the results to line segments, the stimuli used by Sagi and Julesz.

Emerging drugs for the treatment of wound healing.

PubMed

Zielins, Elizabeth R; Brett, Elizabeth A; Luan, Anna; Hu, Michael S; Walmsley, Graham G; Paik, Kevin; Senarath-Yapa, Kshemendra; Atashroo, David A; Wearda, Taylor; Lorenz, H Peter; Wan, Derrick C; Longaker, Michael T

2015-06-01

Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process. A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed. The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.

Investigation of the detection of shallow tunnels using electromagnetic and seismic waves

NASA Astrophysics Data System (ADS)

Counts, Tegan; Larson, Gregg; Gürbüz, Ali Cafer; McClellan, James H.; Scott, Waymond R., Jr.

2007-04-01

Multimodal detection of subsurface targets such as tunnels, pipes, reinforcement bars, and structures has been investigated using both ground-penetrating radar (GPR) and seismic sensors with signal processing techniques to enhance localization capabilities. Both systems have been tested in bi-static configurations but the GPR has been expanded to a multi-static configuration for improved performance. The use of two compatible sensors that sense different phenomena (GPR detects changes in electrical properties while the seismic system measures mechanical properties) increases the overall system's effectiveness in a wider range of soils and conditions. Two experimental scenarios have been investigated in a laboratory model with nearly homogeneous sand. Images formed from the raw data have been enhanced using beamforming inversion techniques and Hough Transform techniques to specifically address the detection of linear targets. The processed data clearly indicate the locations of the buried targets of various sizes at a range of depths.

Localization and Classification of Paddy Field Pests using a Saliency Map and Deep Convolutional Neural Network.

PubMed

Liu, Ziyi; Gao, Junfeng; Yang, Guoguo; Zhang, Huan; He, Yong

2016-02-11

We present a pipeline for the visual localization and classification of agricultural pest insects by computing a saliency map and applying deep convolutional neural network (DCNN) learning. First, we used a global contrast region-based approach to compute a saliency map for localizing pest insect objects. Bounding squares containing targets were then extracted, resized to a fixed size, and used to construct a large standard database called Pest ID. This database was then utilized for self-learning of local image features which were, in turn, used for classification by DCNN. DCNN learning optimized the critical parameters, including size, number and convolutional stride of local receptive fields, dropout ratio and the final loss function. To demonstrate the practical utility of using DCNN, we explored different architectures by shrinking depth and width, and found effective sizes that can act as alternatives for practical applications. On the test set of paddy field images, our architectures achieved a mean Accuracy Precision (mAP) of 0.951, a significant improvement over previous methods.

Localization and Classification of Paddy Field Pests using a Saliency Map and Deep Convolutional Neural Network

PubMed Central

Liu, Ziyi; Gao, Junfeng; Yang, Guoguo; Zhang, Huan; He, Yong

2016-01-01

We present a pipeline for the visual localization and classification of agricultural pest insects by computing a saliency map and applying deep convolutional neural network (DCNN) learning. First, we used a global contrast region-based approach to compute a saliency map for localizing pest insect objects. Bounding squares containing targets were then extracted, resized to a fixed size, and used to construct a large standard database called Pest ID. This database was then utilized for self-learning of local image features which were, in turn, used for classification by DCNN. DCNN learning optimized the critical parameters, including size, number and convolutional stride of local receptive fields, dropout ratio and the final loss function. To demonstrate the practical utility of using DCNN, we explored different architectures by shrinking depth and width, and found effective sizes that can act as alternatives for practical applications. On the test set of paddy field images, our architectures achieved a mean Accuracy Precision (mAP) of 0.951, a significant improvement over previous methods. PMID:26864172

A hierarchical framework for air traffic control

NASA Astrophysics Data System (ADS)

Roy, Kaushik

Air travel in recent years has been plagued by record delays, with over $8 billion in direct operating costs being attributed to 100 million flight delay minutes in 2007. Major contributing factors to delay include weather, congestion, and aging infrastructure; the Next Generation Air Transportation System (NextGen) aims to alleviate these delays through an upgrade of the air traffic control system. Changes to large-scale networked systems such as air traffic control are complicated by the need for coordinated solutions over disparate temporal and spatial scales. Individual air traffic controllers must ensure aircraft maintain safe separation locally with a time horizon of seconds to minutes, whereas regional plans are formulated to efficiently route flows of aircraft around weather and congestion on the order of every hour. More efficient control algorithms that provide a coordinated solution are required to safely handle a larger number of aircraft in a fixed amount of airspace. Improved estimation algorithms are also needed to provide accurate aircraft state information and situational awareness for human controllers. A hierarchical framework is developed to simultaneously solve the sometimes conflicting goals of regional efficiency and local safety. Careful attention is given in defining the interactions between the layers of this hierarchy. In this way, solutions to individual air traffic problems can be targeted and implemented as needed. First, the regional traffic flow management problem is posed as an optimization problem and shown to be NP-Hard. Approximation methods based on aggregate flow models are developed to enable real-time implementation of algorithms that reduce the impact of congestion and adverse weather. Second, the local trajectory design problem is solved using a novel slot-based sector model. This model is used to analyze sector capacity under varying traffic patterns, providing a more comprehensive understanding of how increased automation in NextGen will affect the overall performance of air traffic control. The dissertation also provides solutions to several key estimation problems that support corresponding control tasks. Throughout the development of these estimation algorithms, aircraft motion is modeled using hybrid systems, which encapsulate both the discrete flight mode of an aircraft and the evolution of continuous states such as position and velocity. The target-tracking problem is posed as one of hybrid state estimation, and two new algorithms are developed to exploit structure specific to aircraft motion, especially near airports. First, discrete mode evolution is modeled using state-dependent transitions, in which the likelihood of changing flight modes is dependent on aircraft state. Second, an estimator is designed for systems with limited mode changes, including arrival aircraft. Improved target tracking facilitates increased safety in collision avoidance and trajectory design problems. A multiple-target tracking and identity management algorithm is developed to improve situational awareness for controllers about multiple maneuvering targets in a congested region. Finally, tracking algorithms are extended to predict aircraft landing times; estimated time of arrival prediction is one example of important decision support information for air traffic control.

Registration of PET and CT images based on multiresolution gradient of mutual information demons algorithm for positioning esophageal cancer patients.

PubMed

Jin, Shuo; Li, Dengwang; Wang, Hongjun; Yin, Yong

2013-01-07

Accurate registration of 18F-FDG PET (positron emission tomography) and CT (computed tomography) images has important clinical significance in radiation oncology. PET and CT images are acquired from (18)F-FDG PET/CT scanner, but the two acquisition processes are separate and take a long time. As a result, there are position errors in global and deformable errors in local caused by respiratory movement or organ peristalsis. The purpose of this work was to implement and validate a deformable CT to PET image registration method in esophageal cancer to eventually facilitate accurate positioning the tumor target on CT, and improve the accuracy of radiation therapy. Global registration was firstly utilized to preprocess position errors between PET and CT images, achieving the purpose of aligning these two images on the whole. Demons algorithm, based on optical flow field, has the features of fast process speed and high accuracy, and the gradient of mutual information-based demons (GMI demons) algorithm adds an additional external force based on the gradient of mutual information (GMI) between two images, which is suitable for multimodality images registration. In this paper, GMI demons algorithm was used to achieve local deformable registration of PET and CT images, which can effectively reduce errors between internal organs. In addition, to speed up the registration process, maintain its robustness, and avoid the local extremum, multiresolution image pyramid structure was used before deformable registration. By quantitatively and qualitatively analyzing cases with esophageal cancer, the registration scheme proposed in this paper can improve registration accuracy and speed, which is helpful for precisely positioning tumor target and developing the radiation treatment planning in clinical radiation therapy application.

Registration of PET and CT images based on multiresolution gradient of mutual information demons algorithm for positioning esophageal cancer patients

PubMed Central

Jin, Shuo; Li, Dengwang; Yin, Yong

2013-01-01

Accurate registration of  18F−FDG PET (positron emission tomography) and CT (computed tomography) images has important clinical significance in radiation oncology. PET and CT images are acquired from  18F−FDG PET/CT scanner, but the two acquisition processes are separate and take a long time. As a result, there are position errors in global and deformable errors in local caused by respiratory movement or organ peristalsis. The purpose of this work was to implement and validate a deformable CT to PET image registration method in esophageal cancer to eventually facilitate accurate positioning the tumor target on CT, and improve the accuracy of radiation therapy. Global registration was firstly utilized to preprocess position errors between PET and CT images, achieving the purpose of aligning these two images on the whole. Demons algorithm, based on optical flow field, has the features of fast process speed and high accuracy, and the gradient of mutual information‐based demons (GMI demons) algorithm adds an additional external force based on the gradient of mutual information (GMI) between two images, which is suitable for multimodality images registration. In this paper, GMI demons algorithm was used to achieve local deformable registration of PET and CT images, which can effectively reduce errors between internal organs. In addition, to speed up the registration process, maintain its robustness, and avoid the local extremum, multiresolution image pyramid structure was used before deformable registration. By quantitatively and qualitatively analyzing cases with esophageal cancer, the registration scheme proposed in this paper can improve registration accuracy and speed, which is helpful for precisely positioning tumor target and developing the radiation treatment planning in clinical radiation therapy application. PACS numbers: 87.57.nj, 87.57.Q‐, 87.57.uk PMID:23318381

High-performance C-arm cone-beam CT guidance of thoracic surgery

NASA Astrophysics Data System (ADS)

Schafer, Sebastian; Otake, Yoshito; Uneri, Ali; Mirota, Daniel J.; Nithiananthan, Sajendra; Stayman, J. W.; Zbijewski, Wojciech; Kleinszig, Gerhard; Graumann, Rainer; Sussman, Marc; Siewerdsen, Jeffrey H.

2012-02-01

Localizing sub-palpable nodules in minimally invasive video-assisted thoracic surgery (VATS) presents a significant challenge. To overcome inherent problems of preoperative nodule tagging using CT fluoroscopic guidance, an intraoperative C-arm cone-beam CT (CBCT) image-guidance system has been developed for direct localization of subpalpable tumors in the OR, including real-time tracking of surgical tools (including thoracoscope), and video-CBCT registration for augmentation of the thoracoscopic scene. Acquisition protocols for nodule visibility in the inflated and deflated lung were delineated in phantom and animal/cadaver studies. Motion compensated reconstruction was implemented to account for motion induced by the ventilated contralateral lung. Experience in CBCT-guided targeting of simulated lung nodules included phantoms, porcine models, and cadavers. Phantom studies defined low-dose acquisition protocols providing contrast-to-noise ratio sufficient for lung nodule visualization, confirmed in porcine specimens with simulated nodules (3-6mm diameter PE spheres, ~100-150HU contrast, 2.1mGy). Nodule visibility in CBCT of the collapsed lung, with reduced contrast according to air volume retention, was more challenging, but initial studies confirmed visibility using scan protocols at slightly increased dose (~4.6-11.1mGy). Motion compensated reconstruction employing a 4D deformation map in the backprojection process reduced artifacts associated with motion blur. Augmentation of thoracoscopic video with renderings of the target and critical structures (e.g., pulmonary artery) showed geometric accuracy consistent with camera calibration and the tracking system (2.4mm registration error). Initial results suggest a potentially valuable role for CBCT guidance in VATS, improving precision in minimally invasive, lungconserving surgeries, avoid critical structures, obviate the burdens of preoperative localization, and improve patient safety.

What makes British general practitioners take part in a quality improvement scheme?

PubMed

Spooner, A; Chapple, A; Roland, M

2001-07-01

To understand the reasons for the apparent success of a quality improvement scheme designed to produce widespread changes in chronic disease management in primary care. Purposeful sample of 36 primary care staff, managers and specialists. Qualitative analysis of 27 interviews in East Kent Health Authority area, where, over a three-year period, more than three-quarters of general practitioners (GPs) and enrolled in a quality improvement programme which required them to meet challenging chronic disease management targets (PRImary Care Clinical Effectiveness--PRICCE). Major changes in clinical practice appeared to have taken place as a result of participation in PRICCE. The scheme was significantly dependent on leadership from the health authority and on local professional support. Factors that motivated GPs to take part in the project included: a desire to improve patient care; financial incentives; maintenance of professional autonomy in how to reach the targets; maintenance of professional pride; and peer pressure. Good teamworking was essential to successful completion of the project and often improved as a result of taking part. The scheme included a combination of interventions known to be effective in producing professional behavioural change. When managerial vision is aligned to professional values, and combined with a range of interventions known to influence professional behaviour including financial incentives, substantial changes in clinical practice can result. Lessons are drawn for future quality improvement programmes in the National Health Service.

Inter-kingdom prediction certainty evaluation of protein subcellular localization tools: microbial pathogenesis approach for deciphering host microbe interaction.

PubMed

Khan, Abdul Arif; Khan, Zakir; Kalam, Mohd Abul; Khan, Azmat Ali

2018-01-01

Microbial pathogenesis involves several aspects of host-pathogen interactions, including microbial proteins targeting host subcellular compartments and subsequent effects on host physiology. Such studies are supported by experimental data, but recent detection of bacterial proteins localization through computational eukaryotic subcellular protein targeting prediction tools has also come into practice. We evaluated inter-kingdom prediction certainty of these tools. The bacterial proteins experimentally known to target host subcellular compartments were predicted with eukaryotic subcellular targeting prediction tools, and prediction certainty was assessed. The results indicate that these tools alone are not sufficient for inter-kingdom protein targeting prediction. The correct prediction of pathogen's protein subcellular targeting depends on several factors, including presence of localization signal, transmembrane domain and molecular weight, etc., in addition to approach for subcellular targeting prediction. The detection of protein targeting in endomembrane system is comparatively difficult, as the proteins in this location are channelized to different compartments. In addition, the high specificity of training data set also creates low inter-kingdom prediction accuracy. Current data can help to suggest strategy for correct prediction of bacterial protein's subcellular localization in host cell. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The fate of nanocarriers as nanomedicines in vivo: important considerations and biological barriers to overcome.

PubMed

Moros, M; Mitchell, S G; Grazú, V; de la Fuente, J M

2013-01-01

Many pharmaceuticals on the market suffer from two significant limitations to their activity: lack of specificity toward the pathological site and poor aqueous solubility. Both factors therefore require the application of a large total dose of a drug to achieve high local concentration, causing numerous off-target toxic effects. Consequently, the grand aim of targeted drug delivery - the often-referred "magic bullet" - promises to improve drug concentration at the target site and maximize therapeutic response. Nanomaterial drug delivery systems have been explored extensively in the recent years for just this purpose. In the field of medicine, nanocarriers (NCs) have the potential to improve the biodistribution and pharmacokinetic characteristics of drugs, thereby reducing side effects while improving the therapeutic effect of drugs. Many nanomaterials are exquisitely designed and possess potent properties, yet it is extremely important to note that a general understanding of the interaction of nanomaterials with biological systems is essential for any such model properties to be effective in vivo, since the body presents a host of biological 'barriers' that will be encountered drug NCs. This review offers a general overview of the different biological obstacles that a NC must negotiate before it can carry out its desired role as a medicinal agent. From this standpoint we suggest aspects that should be considered for the rational design of novel nanomaterials possessing physicochemical properties that are appropriate for therapeutic or theragnostic applications.

Adaptive AOA-aided TOA self-positioning for mobile wireless sensor networks.

PubMed

Wen, Chih-Yu; Chan, Fu-Kai

2010-01-01

Location-awareness is crucial and becoming increasingly important to many applications in wireless sensor networks. This paper presents a network-based positioning system and outlines recent work in which we have developed an efficient principled approach to localize a mobile sensor using time of arrival (TOA) and angle of arrival (AOA) information employing multiple seeds in the line-of-sight scenario. By receiving the periodic broadcasts from the seeds, the mobile target sensors can obtain adequate observations and localize themselves automatically. The proposed positioning scheme performs location estimation in three phases: (I) AOA-aided TOA measurement, (II) Geometrical positioning with particle filter, and (III) Adaptive fuzzy control. Based on the distance measurements and the initial position estimate, adaptive fuzzy control scheme is applied to solve the localization adjustment problem. The simulations show that the proposed approach provides adaptive flexibility and robust improvement in position estimation.

Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer.

PubMed

Churilla, Thomas M; Weiss, Stephanie E

2018-05-07

To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC). Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1-4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5-15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy. The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

Anti-CD38 antibody therapy: windows of opportunity yielded by the functional characteristics of the target molecule.

PubMed

Chillemi, Antonella; Zaccarello, Gianluca; Quarona, Valeria; Ferracin, Manuela; Ghimenti, Chiara; Massaia, Massimo; Horenstein, Alberto L; Malavasi, Fabio

2013-05-20

In vivo use of monoclonal antibodies (mAbs) has become a mainstay of routine clinical practice in the treatment of various human diseases. A number of molecules can serve as targets, according to the condition being treated. Now entering human clinical trials, CD38 molecule is a particularly attractive target because of its peculiar pattern of expression and its twin role as receptor and ectoenzyme. This review provides a range of analytical perspectives on the current progress in and challenges to anti-CD38 mAb therapy. We present a synopsis of the evidence available on CD38, particularly in myeloma and chronic lymphocytic leukemia (CLL). Our aim is to make the data from basic science helpful and accessible to a diverse clinical audience and, at the same time, to improve its potential for in vivo use. The topics covered include tissue distribution and signal implementation by mAb ligation and the possibility of increasing cell density on target cells by exploiting information about the molecule's regulation in combination with drugs approved for in vivo use. Also analyzed is the behavior of CD38 as an enzyme: CD38 is a component of a pathway leading to the production of adenosine in the tumor microenvironment, thus inducing local anergy. Consequently, not only might CD38 be a prime target for mAb-mediated therapy, but its functional block may contribute to general improvement in cancer immunotherapy and outcomes.

A Robust Wireless Sensor Network Localization Algorithm in Mixed LOS/NLOS Scenario.

PubMed

Li, Bing; Cui, Wei; Wang, Bin

2015-09-16

Localization algorithms based on received signal strength indication (RSSI) are widely used in the field of target localization due to its advantages of convenient application and independent from hardware devices. Unfortunately, the RSSI values are susceptible to fluctuate under the influence of non-line-of-sight (NLOS) in indoor space. Existing algorithms often produce unreliable estimated distances, leading to low accuracy and low effectiveness in indoor target localization. Moreover, these approaches require extra prior knowledge about the propagation model. As such, we focus on the problem of localization in mixed LOS/NLOS scenario and propose a novel localization algorithm: Gaussian mixed model based non-metric Multidimensional (GMDS). In GMDS, the RSSI is estimated using a Gaussian mixed model (GMM). The dissimilarity matrix is built to generate relative coordinates of nodes by a multi-dimensional scaling (MDS) approach. Finally, based on the anchor nodes' actual coordinates and target's relative coordinates, the target's actual coordinates can be computed via coordinate transformation. Our algorithm could perform localization estimation well without being provided with prior knowledge. The experimental verification shows that GMDS effectively reduces NLOS error and is of higher accuracy in indoor mixed LOS/NLOS localization and still remains effective when we extend single NLOS to multiple NLOS.

Space moving target detection and tracking method in complex background

NASA Astrophysics Data System (ADS)

Lv, Ping-Yue; Sun, Sheng-Li; Lin, Chang-Qing; Liu, Gao-Rui

2018-06-01

The background of the space-borne detectors in real space-based environment is extremely complex and the signal-to-clutter ratio is very low (SCR ≈ 1), which increases the difficulty for detecting space moving targets. In order to solve this problem, an algorithm combining background suppression processing based on two-dimensional least mean square filter (TDLMS) and target enhancement based on neighborhood gray-scale difference (GSD) is proposed in this paper. The latter can filter out most of the residual background clutter processed by the former such as cloud edge. Through this procedure, both global and local SCR have obtained substantial improvement, indicating that the target has been greatly enhanced. After removing the detector's inherent clutter region through connected domain processing, the image only contains the target point and the isolated noise, in which the isolated noise could be filtered out effectively through multi-frame association. The proposed algorithm in this paper has been compared with some state-of-the-art algorithms for moving target detection and tracking tasks. The experimental results show that the performance of this algorithm is the best in terms of SCR gain, background suppression factor (BSF) and detection results.

Towards accurate localization: long- and short-term correlation filters for tracking

NASA Astrophysics Data System (ADS)

Li, Minglangjun; Tian, Chunna

2018-04-01

Visual tracking is a challenging problem, especially using a single model. In this paper, we propose a discriminative correlation filter (DCF) based tracking approach that exploits both the long-term and short-term information of the target, named LSTDCF, to improve the tracking performance. In addition to a long-term filter learned through the whole sequence, a short-term filter is trained using only features extracted from most recent frames. The long-term filter tends to capture more semantics of the target as more frames are used for training. However, since the target may undergo large appearance changes, features extracted around the target in non-recent frames prevent the long-term filter from locating the target in the current frame accurately. In contrast, the short-term filter learns more spatial details of the target from recent frames but gets over-fitting easily. Thus the short-term filter is less robust to handle cluttered background and prone to drift. We take the advantage of both filters and fuse their response maps to make the final estimation. We evaluate our approach on a widely-used benchmark with 100 image sequences and achieve state-of-the-art results.

Signal detection theory applied to three visual search tasks--identification, yes/no detection and localization.

PubMed

Cameron, E Leslie; Tai, Joanna C; Eckstein, Miguel P; Carrasco, Marisa

2004-01-01

Adding distracters to a display impairs performance on visual tasks (i.e. the set-size effect). While keeping the display characteristics constant, we investigated this effect in three tasks: 2 target identification, yes-no detection with 2 targets, and 8-alternative localization. A Signal Detection Theory (SDT) model, tailored for each task, accounts for the set-size effects observed in identification and localization tasks, and slightly under-predicts the set-size effect in a detection task. Given that sensitivity varies as a function of spatial frequency (SF), we measured performance in each of these three tasks in neutral and peripheral precue conditions for each of six spatial frequencies (0.5-12 cpd). For all spatial frequencies tested, performance on the three tasks decreased as set size increased in the neutral precue condition, and the peripheral precue reduced the effect. Larger set-size effects were observed at low SFs in the identification and localization tasks. This effect can be described using the SDT model, but was not predicted by it. For each of these tasks we also established the extent to which covert attention modulates performance across a range of set sizes. A peripheral precue substantially diminished the set-size effect and improved performance, even at set size 1. These results provide support for distracter exclusion, and suggest that signal enhancement may also be a mechanism by which covert attention can impose its effect.

Targeting Adults Who Provide Alcohol to Underage Youth: Results from a National Survey of Local Law Enforcement Agencies

PubMed Central

Jones-Webb, Rhonda; Toomey, Traci L.; Lenk, Kathleen M.; Nelson, Toben F.; Erickson, Darin J.

2014-01-01

Objective We investigated what local enforcement agencies are doing to target adults who provide alcohol to underage youth; what types of enforcement activities are being conducted to target adult providers; and factors that encourage enforcement activities that target adult providers. Method We surveyed 1056 local law enforcement agencies in the U.S. and measured whether or not the agency conducted enforcement activities that target adults who provide alcohol to underage youth. We also measured whether certain agency and jurisdiction characteristics were associated with enforcement activities that target adults who provide alcohol to underage youth. Results Less than half (42%) of local enforcement agencies conducted enforcement efforts targeting adults who provide alcohol to underage youth. Agencies that conducted the enforcement activities targeting adult providers were significantly more likely to have a full time officer specific to alcohol enforcement, a division specific to alcohol enforcement, a social host law, and to perceive underage drinking was very common. Conclusions Results suggest that targeting social providers (i.e., adults over 21 years of age) will require greater law enforcement resources, implementation of underage drinking laws (e.g., social host policies), and changing perceptions among law enforcement regarding underage drinking. Future studies are needed to identify the most effective enforcement efforts and to examine how enforcement efforts are prospectively linked to alcohol consumption. PMID:25466432

Targeting adults who provide alcohol to underage youth: results from a national survey of local law enforcement agencies.

PubMed

Jones-Webb, Rhonda; Toomey, Traci L; Lenk, Kathleen M; Nelson, Toben F; Erickson, Darin J

2015-06-01

We investigated what local enforcement agencies are doing to target adults who provide alcohol to underage youth; what types of enforcement activities are being conducted to target adult providers; and factors that encourage enforcement activities that target adult providers. We surveyed 1,056 local law enforcement agencies in the US and measured whether or not the agency conducted enforcement activities that target adults who provide alcohol to underage youth. We also measured whether certain agency and jurisdiction characteristics were associated with enforcement activities that target adults who provide alcohol to underage youth. Less than half (42%) of local enforcement agencies conducted enforcement efforts targeting adults who provide alcohol to underage youth. Agencies that conducted the enforcement activities targeting adult providers were significantly more likely to have a full time officer specific to alcohol enforcement, a division specific to alcohol enforcement, a social host law, and to perceive underage drinking was very common. Results suggest that targeting social providers (i.e., adults over 21 years of age) will require greater law enforcement resources, implementation of underage drinking laws (e.g., social host policies), and changing perceptions among law enforcement regarding underage drinking. Future studies are needed to identify the most effective enforcement efforts and to examine how enforcement efforts are prospectively linked to alcohol consumption.

Volumetric Image Guidance Using Carina vs Spine as Registration Landmarks for Conventionally Fractionated Lung Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lavoie, Caroline; Higgins, Jane; Bissonnette, Jean-Pierre

2012-12-01

Purpose: To compare the relative accuracy of 2 image guided radiation therapy methods using carina vs spine as landmarks and then to identify which landmark is superior relative to tumor coverage. Methods and Materials: For 98 lung patients, 2596 daily image-guidance cone-beam computed tomography scans were analyzed. Tattoos were used for initial patient alignment; then, spine and carina registrations were performed independently. A separate analysis assessed the adequacy of gross tumor volume, internal target volume, and planning target volume coverage on cone-beam computed tomography using the initial, middle, and final fractions of radiation therapy. Coverage was recorded for primary tumormore » (T), nodes (N), and combined target (T+N). Three scenarios were compared: tattoos alignment, spine registration, and carina registration. Results: Spine and carina registrations identified setup errors {>=}5 mm in 35% and 46% of fractions, respectively. The mean vector difference between spine and carina matching had a magnitude of 3.3 mm. Spine and carina improved combined target coverage, compared with tattoos, in 50% and 34% (spine) to 54% and 46% (carina) of the first and final fractions, respectively. Carina matching showed greater combined target coverage in 17% and 23% of fractions for the first and final fractions, respectively; with spine matching, this was only observed in 4% (first) and 6% (final) of fractions. Carina matching provided superior nodes coverage at the end of radiation compared with spine matching (P=.0006), without compromising primary tumor coverage. Conclusion: Frequent patient setup errors occur in locally advanced lung cancer patients. Spine and carina registrations improved combined target coverage throughout the treatment course, but carina matching provided superior combined target coverage.« less

What must be the accuracy and target of optical sensor systems for patient monitoring?

NASA Astrophysics Data System (ADS)

Frank, Klaus H.; Kessler, Manfred D.

2002-06-01

Although the treatment in the intensive care unit has improved in recent years enabling greater surgical engagements and improving patients survival rate, no adequate monitoring is available in imminent severe pathological cases. Otherwise such kind of monitoring is necessary for early or prophylactic treatment in order to avoid or reduce the severity of the disease and protect the patient from sepsis or multiple organ failure. In these cases the common monitoring is limited, because clinical physiological and laboratory parameters indicate either the situation of macro-circulation or late disturbances of microcirculation, which arise previously on sub-cellular level. Optical sensor systems enable to reveal early variations in local capillary flow. The correlation between clinical parameters and changes in condition of oxygenation as a function of capillary flow disturbances is meaningful for the further treatment. The target should be to develop a predictive parameter, which is useful for detection and follow-up of changes in circulation.

Mapping local variation in educational attainment across Africa

NASA Astrophysics Data System (ADS)

Graetz, Nicholas; Friedman, Joseph; Osgood-Zimmerman, Aaron; Burstein, Roy; Biehl, Molly H.; Shields, Chloe; Mosser, Jonathan F.; Casey, Daniel C.; Deshpande, Aniruddha; Earl, Lucas; Reiner, Robert C.; Ray, Sarah E.; Fullman, Nancy; Levine, Aubrey J.; Stubbs, Rebecca W.; Mayala, Benjamin K.; Longbottom, Joshua; Browne, Annie J.; Bhatt, Samir; Weiss, Daniel J.; Gething, Peter W.; Mokdad, Ali H.; Lim, Stephen S.; Murray, Christopher J. L.; Gakidou, Emmanuela; Hay, Simon I.

2018-03-01

Educational attainment for women of reproductive age is linked to reduced child and maternal mortality, lower fertility and improved reproductive health. Comparable analyses of attainment exist only at the national level, potentially obscuring patterns in subnational inequality. Evidence suggests that wide disparities between urban and rural populations exist, raising questions about where the majority of progress towards the education targets of the Sustainable Development Goals is occurring in African countries. Here we explore within-country inequalities by predicting years of schooling across five by five kilometre grids, generating estimates of average educational attainment by age and sex at subnational levels. Despite marked progress in attainment from 2000 to 2015 across Africa, substantial differences persist between locations and sexes. These differences have widened in many countries, particularly across the Sahel. These high-resolution, comparable estimates improve the ability of decision-makers to plan the precisely targeted interventions that will be necessary to deliver progress during the era of the Sustainable Development Goals.

New Local, National and Regional Cereal Price Indices for Improved Identification of Food Insecurity

NASA Technical Reports Server (NTRS)

Brown, Molly E.; Tondel, Fabien; Thorne, Jennifer A.; Essam, Timothy; Mann, Bristol F.; Stabler, Blake; Eilerts, Gary

2011-01-01

Large price increases over a short time period can be indicative of a deteriorating food security situation. Food price indices developed by the United Nations Food and Agriculture Organization (FAO) are used to monitor food price trends at a global level, but largely reflect supply and demand conditions in export markets. However, reporting by the United States Agency for International Development (USAID)'s Famine Early Warning Systems Network (FEWS NET) indicates that staple cereal prices in many markets of the developing world, especially in surplus-producing areas, often have a delayed and variable response to international export market price trends. Here we present new price indices compiled for improved food security monitoring and assessment, and specifically for monitoring conditions of food access across diverse food insecure regions. We found that cereal price indices constructed using market prices within a food insecure region showed significant differences from the international cereals price, and had a variable price dispersion across markets within each marketshed. Using satellite-derived remote sensing information that estimates local production and the FAO Cereals Index as predictors, we were able to forecast movements of the local or national price indices in the remote, arid and semi-arid countries of the 38 countries examined. This work supports the need for improved decision-making about targeted aid and humanitarian relief, by providing earlier early warning of food security crises.

Quantifying density cues in grouping displays.

PubMed

Machilsen, Bart; Wagemans, Johan; Demeyer, Maarten

2016-09-01

Perceptual grouping processes are typically studied using sparse displays of spatially separated elements. Unless the grouping cue of interest is a proximity cue, researchers will want to ascertain that such a cue is absent from the display. Various solutions to this problem have been employed in the literature; however, no validation of these methods exists. Here, we test a number of local density metrics both through their performance as constrained ideal observer models, and through a comparison with a large dataset of human detection trials. We conclude that for the selection of stimuli without a density cue, the Voronoi density metric is preferable, especially if combined with a measurement of the distance to each element's nearest neighbor. We offer the entirety of the dataset as a benchmark for the evaluation of future, possibly improved, metrics. With regard to human processes of grouping by proximity, we found observers to be insensitive to target groupings that are more sparse than the surrounding distractor elements, and less sensitive to regularity cues in element positioning than to local clusterings of target elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

Target development for diversified irradiations at a medical cyclotron.

PubMed

Spellerberg, S; Scholten, B; Spahn, I; Bolten, W; Holzgreve, M; Coenen, H H; Qaim, S M

2015-10-01

The irradiation facility at an old medical cyclotron (Ep=17 MeV; Ed=10 MeV) was upgraded by extending the beam line and incorporation of solid state targetry. Tests performed to check the quality of the available beam are outlined. Results on nuclear data measurements and improvement of radiochemical separations are described. Using solid targets, with the proton beam falling at a slanting angle of 20°, a few radionuclides, e.g. (75)Se, (120)I, (124)I, etc. were produced with medium currents (up to 20 µA) in no-carrier-added form in quantities sufficient for local use. The extended irradiation facility has considerably enhanced the utility of the medical cyclotron. Copyright © 2015 Elsevier Ltd. All rights reserved.

Collaboration between local health and local government agencies for health improvement.

PubMed

Hayes, Sara L; Mann, Mala K; Morgan, Fiona M; Kitcher, Hilary; Kelly, Mark J; Weightman, Alison L

2011-06-15

In many countries, national, regional and local inter- and intra-agency collaborations have been introduced in order to improve health outcomes. Evidence is needed on the effectiveness of locally-developed partnerships which target changes in individual health outcomes and behaviours. To evaluate the effects of interagency collaboration between local health and local government agencies on health outcomes. Twenty-five databases were searched using a highly sensitive search strategy. 'Snowballing' methods were also used, including expert contact, website searching and reference list follow up. Randomized controlled trials (RCTs), controlled clinical trials (CCTs), controlled before-and-after studies (CBAs) and interrupted time series (ITS) where the study reported on interagency collaboration between health and local government agencies. Studies were selected independently in duplicate by two of five authors. From the team of five review authors, two authors independently conducted data extraction and assessed risk of bias for each study. Eleven studies were identified, presenting information on a total of 26,686 participants. Owing to the heterogeneity between studies a narrative synthesis was undertaken. The included studies covered a range of topics. Six studies examined mental health initiatives, of which one study showed health benefit; four showed modest improvement in one or more of the outcomes measured, but no clear overall health gain; and one study showed no evidence of health gain. Two studies were related to lifestyle improvements of which one failed to show health gains for the intervention population, while the other showed more unhealthy lifestyle behaviours persisting in the intervention population. Three studies were related to chronic disease management and all three failed to demonstrate health gains. Collaboration between local health and local government is commonly considered best practice. However, the review did not identify any reliable evidence that inter‑agency collaboration, compared to standard services, leads to health improvement. A few studies identified component benefits but these were not reflected in overall outcome scores and could have resulted from the use of significant additional resources. Although agencies appear enthusiastic about collaboration, methodological flaws in the primary studies and incomplete implementation of initiatives have prevented the development of a strong evidence base. If these flaws are addressed in future studies (for example by providing greater detail on the implementation of programs, using more robust designs, with integrated process evaluations and measurement of health outcomes) it could provide a better understanding of what might work and why.When updating this review, we will analyse any partnership or process evaluations of our included studies to try to identify markers of success in local collaborative partnerships that could inform policy developments in the future.

[The role of microRNAs in head and neck squamous cell carcinoma : Biomarkers for prognosis, therapy selection, and novel therapeutics].

PubMed

Heß, A K; Weichert, W; Budach, V; Tinhofer, I

2016-05-01

Despite recent advances in radiochemotherapy, treatment of locally advanced head and neck squamous cell carcinoma is still challenging, and survival rates have improved only slightly. This is due to the high frequency of metastases and local and/or regional tumor recurrences that have acquired radio- or chemoresistance. MiRNAs regulate diverse processes in tumorigenesis, metastasis, and therapy resistance in head and neck squamous cell carcinoma. Hence, miRNAs are highly valued in biomarker studies. Establishment of the miRNA profiles of oropharyngeal tumors enables personalized treatment selection, since expression of distinct miRNAs can predict the response to two different radiochemotherapy regimens. Development of novel miRNA therapeutics has a high clinical potential for further improving treatment of cancerous disease. The use of nanoparticles with distinct surface modifications as miRNA vectors permits prolonged bioavailability, high efficacy in tumor targeting, and low toxicity. Nevertheless, the efficacy of miRNA therapy has only been shown in animal models to date.

Electromagnetic tracking of flexible robotic catheters enables "assisted navigation" and brings automation to endovascular navigation in an in vitro study.

PubMed

Schwein, Adeline; Kramer, Benjamin; Chinnadurai, Ponraj; Virmani, Neha; Walker, Sean; O'Malley, Marcia; Lumsden, Alan B; Bismuth, Jean

2018-04-01

Combining three-dimensional (3D) catheter control with electromagnetic (EM) tracking-based navigation significantly reduced fluoroscopy time and improved robotic catheter movement quality in a previous in vitro pilot study. The aim of this study was to expound on previous results and to expand the value of EM tracking with a novel feature, assistednavigation, allowing automatic catheter orientation and semiautomatic vessel cannulation. Eighteen users navigated a robotic catheter in an aortic aneurysm phantom using an EM guidewire and a modified 9F robotic catheter with EM sensors at the tip of both leader and sheath. All users cannulated two targets, the left renal artery and posterior gate, using four visualization modes: (1) Standard fluoroscopy (control). (2) 2D biplane fluoroscopy showing real-time virtual catheter localization and orientation from EM tracking. (3) 2D biplane fluoroscopy with novel EM assisted navigation allowing the user to define the target vessel. The robotic catheter orients itself automatically toward the target; the user then only needs to advance the guidewire following this predefined optimized path to catheterize the vessel. Then, while advancing the catheter over the wire, the assisted navigation automatically modifies catheter bending and rotation in order to ensure smooth progression, avoiding loss of wire access. (4) Virtual 3D representation of the phantom showing real-time virtual catheter localization and orientation. Standard fluoroscopy was always available; cannulation and fluoroscopy times were noted for every mode and target cannulation. Quality of catheter movement was assessed by measuring the number of submovements of the catheter using the 3D coordinates of the EM sensors. A t-test was used to compare the standard fluoroscopy mode against EM tracking modes. EM tracking significantly reduced the mean fluoroscopy time (P < .001) and the number of submovements (P < .02) for both cannulation tasks. For the posterior gate, mean cannulation time was also significantly reduced when using EM tracking (P < .001). The use of novel EM assisted navigation feature (mode 3) showed further reduced cannulation time for the posterior gate (P = .002) and improved quality of catheter movement for the left renal artery cannulation (P = .021). These results confirmed the findings of a prior study that highlighted the value of combining 3D robotic catheter control and 3D navigation to improve safety and efficiency of endovascular procedures. The novel EM assisted navigation feature augments the robotic master/slave concept with automated catheter orientation toward the target and shows promising results in reducing procedure time and improving catheter motion quality. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Tumor-associated macrophages: implications in cancer immunotherapy.

PubMed

Petty, Amy J; Yang, Yiping

2017-03-01

Tumor-associated macrophages (TAMs), representing most of the leukocyte population in solid tumors, demonstrate great phenotypic heterogeneity and diverse functional capabilities under the influence of the local tumor microenvironment. These anti-inflammatory and protumorigenic macrophages modulate the local microenvironment to facilitate tumor growth and metastasis. In this review, we examine the origin of TAMs and the complex regulatory networks within the tumor microenvironment that facilitate the polarization of TAMs toward a protumoral phenotype. More extensively, we evaluate the mechanisms by which TAMs mediate angiogenesis, metastasis, chemotherapeutic resistance and immune evasion. Lastly, we will highlight novel interventional strategies targeting TAMs in preclinical studies and in early clinical trials that have significant potential in improving efficacy of current chemotherapeutic and/or immunotherapeutic approaches.

Focal therapy as primary treatment for localized prostate cancer: definition, needs and future.

PubMed

Ouzzane, Adil; Betrouni, Nacim; Valerio, Massimo; Rastinehad, Ardeshir; Colin, Pierre; Ploussard, Guillaume

2017-04-01

Focal therapy (FT) may offer a promising treatment option in the field of low to intermediate risk localized prostate cancer. The aim of this concept is to combine minimal morbidity with cancer control as well as maintain the possibility of retreatment. Recent advances in MRI and targeted biopsy has improved the diagnostic pathway of prostate cancer and increased the interest in FT. However, before implementation of FT in routine clinical practice, several challenges are still to overcome including patient selection, treatment planning, post-therapy monitoring and definition of oncologic outcome surrogates. In this article, relevant questions regarding the key steps of FT are critically discussed and the main available energy modalities are analyzed taking into account their advantages and unmet needs.

Navigation system for minimally invasive esophagectomy: experimental study in a porcine model.

PubMed

Nickel, Felix; Kenngott, Hannes G; Neuhaus, Jochen; Sommer, Christof M; Gehrig, Tobias; Kolb, Armin; Gondan, Matthias; Radeleff, Boris A; Schaible, Anja; Meinzer, Hans-Peter; Gutt, Carsten N; Müller-Stich, Beat-Peter

2013-10-01

Navigation systems potentially facilitate minimally invasive esophagectomy and improve patient outcome by improving intraoperative orientation, position estimation of instruments, and identification of lymph nodes and resection margins. The authors' self-developed navigation system is highly accurate in static environments. This study aimed to test the overall accuracy of the navigation system in a realistic operating room scenario and to identify the different sources of error altering accuracy. To simulate a realistic environment, a porcine model (n = 5) was used with endoscopic clips in the esophagus as navigation targets. Computed tomography imaging was followed by image segmentation and target definition with the medical imaging interaction toolkit software. Optical tracking was used for registration and localization of animals and navigation instruments. Intraoperatively, the instrument was displayed relative to segmented organs in real time. The target registration error (TRE) of the navigation system was defined as the distance between the target and the navigation instrument tip. The TRE was measured on skin targets with the animal in the 0° supine and 25° anti-Trendelenburg position and on the esophagus during laparoscopic transhiatal preparation. On skin targets, the TRE was significantly higher in the 25° position, at 14.6 ± 2.7 mm, compared with the 0° position, at 3.2 ± 1.3 mm. The TRE on the esophagus was 11.2 ± 2.4 mm. The main source of error was soft tissue deformation caused by intraoperative positioning, pneumoperitoneum, surgical manipulation, and tissue dissection. The navigation system obtained acceptable accuracy with a minimally invasive transhiatal approach to the esophagus in a realistic experimental model. Thus the system has the potential to improve intraoperative orientation, identification of lymph nodes and adequate resection margins, and visualization of risk structures. Compensation methods for soft tissue deformation may lead to an even more accurate navigation system in the future.

'Where' and 'what' in visual search.

PubMed

Atkinson, J; Braddick, O J

1989-01-01

A line segment target can be detected among distractors of a different orientation by a fast 'preattentive' process. One view is that this depends on detection of a 'feature gradient', which enables subjects to locate where the target is without necessarily identifying what it is. An alternative view is that a target can be identified as distinctive in a particular 'feature map' without subjects knowing where it is in that map. Experiments are reported in which briefly exposed arrays of line segments were followed by a pattern mask, and the threshold stimulus-mask interval determined for three tasks: 'what'--subjects reported whether the target was vertical or horizontal among oblique distractors; 'coarse where'--subjects reported whether the target was in the upper or lower half of the array; 'fine where'--subjects reported whether or not the target was in a set of four particular array positions. The threshold interval was significantly lower for the 'coarse where' than for the 'what' task, indicating that, even though localization in this task depends on the target's orientation difference, this localization is possible without absolute identification of target orientation. However, for the 'fine where' task, intervals as long as or longer than those for the 'what' task were required. It appears either that different localization processes work at different levels of resolution, or that a single localization process, independent of identification, can increase its resolution at the expense of processing speed. These possibilities are discussed in terms of distinct neural representations of the visual field and fixed or variable localization processes acting upon them.

Dual pancreas- and lung-targeting therapy for local and systemic complications of acute pancreatitis mediated by a phenolic propanediamine moiety.

PubMed

Li, Jianbo; Zhang, Jinjie; Fu, Yao; Sun, Xun; Gong, Tao; Jiang, Jinghui; Zhang, Zhirong

2015-08-28

To inhibit both the local and systemic complications with acute pancreatitis, an effective therapy requires a drug delivery system that can efficiently overcome the blood-pancreas barrier while achieving lung-specific accumulation. Here, we report the first dual pancreas- and lung-targeting therapeutic strategy mediated by a phenolic propanediamine moiety for the treatment of acute pancreatitis. Using the proposed dual-targeting ligand, an anti-inflammatory compound Rhein has been tailored to preferentially accumulate in the pancreas and lungs with rapid distribution kinetics, excellent tissue-penetrating properties and minimum toxicity. Accordingly, the drug-ligand conjugate remarkably downregulated the proinflammatory cytokines in the target organs thus effectively inhibiting local pancreatic and systemic inflammation in rats. The dual-specific targeting therapeutic strategy may help pave the way for targeted drug delivery to treat complicated inflammatory diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Combined clinical and home rehabilitation: case report of an integrated knowledge-to-action study in a Dutch rehabilitation stroke unit.

PubMed

Nanninga, Christa S; Postema, Klaas; Schönherr, Marleen C; van Twillert, Sacha; Lettinga, Ant T

2015-04-01

There is growing awareness that the poor uptake of evidence in health care is not a knowledge-transfer problem but rather one of knowledge production. This issue calls for re-examination of the evidence produced and assumptions that underpin existing knowledge-to-action (KTA) activities. Accordingly, it has been advocated that KTA studies should treat research knowledge and local practical knowledge with analytical impartiality. The purpose of this case report is to illustrate the complexities in an evidence-informed improvement process of organized stroke care in a local rehabilitation setting. A participatory action approach was used to co-create knowledge and engage local therapists in a 2-way knowledge translation and multidirectional learning process. Evidence regarding rehabilitation stroke units was applied in a straightforward manner, as the setting met the criteria articulated in stroke unit reviews. Evidence on early supported discharge (ESD) could not be directly applied because of differences in target group and implementation environment between the local and reviewed settings. Early supported discharge was tailored to the needs of patients severely affected by stroke admitted to the local rehabilitation stroke unit by combining clinical and home rehabilitation (CCHR). Local therapists welcomed CCHR because it helped them make their task-specific training truly context specific. Key barriers to implementation were travel time, logistical problems, partitioning walls between financing streams, and legislative procedures. Improving local settings with available evidence is not a straightforward application process but rather a matter of searching, logical reasoning, and creatively working with heterogeneous knowledge sources in partnership with different stakeholders. Multiple organizational levels need to be addressed rather than focusing on therapists as sole site of change. © 2015 American Physical Therapy Association.

Super-resolution optical telescopes with local light diffraction shrinkage

PubMed Central

Wang, Changtao; Tang, Dongliang; Wang, Yanqin; Zhao, Zeyu; Wang, Jiong; Pu, Mingbo; Zhang, Yudong; Yan, Wei; Gao, Ping; Luo, Xiangang

2015-01-01

Suffering from giant size of objective lenses and infeasible manipulations of distant targets, telescopes could not seek helps from present super-resolution imaging, such as scanning near-field optical microscopy, perfect lens and stimulated emission depletion microscopy. In this paper, local light diffraction shrinkage associated with optical super-oscillatory phenomenon is proposed for real-time and optically restoring super-resolution imaging information in a telescope system. It is found that fine target features concealed in diffraction-limited optical images of a telescope could be observed in a small local field of view, benefiting from a relayed metasurface-based super-oscillatory imaging optics in which some local Fourier components beyond the cut-off frequency of telescope could be restored. As experimental examples, a minimal resolution to 0.55 of Rayleigh criterion is obtained, and imaging complex targets and large targets by superimposing multiple local fields of views are demonstrated as well. This investigation provides an access for real-time, incoherent and super-resolution telescopes without the manipulation of distant targets. More importantly, it gives counterintuitive evidence to the common knowledge that relayed optics could not deliver more imaging details than objective systems. PMID:26677820

Locally Bayesian Learning with Applications to Retrospective Revaluation and Highlighting

ERIC Educational Resources Information Center

Kruschke, John K.

2006-01-01

A scheme is described for locally Bayesian parameter updating in models structured as successions of component functions. The essential idea is to back-propagate the target data to interior modules, such that an interior component's target is the input to the next component that maximizes the probability of the next component's target. Each layer…

The effect of visual context on manual localization of remembered targets

NASA Technical Reports Server (NTRS)

Barry, S. R.; Bloomberg, J. J.; Huebner, W. P.

1997-01-01

This paper examines the contribution of egocentric cues and visual context to manual localization of remembered targets. Subjects pointed in the dark to the remembered position of a target previously viewed without or within a structured visual scene. Without a remembered visual context, subjects pointed to within 2 degrees of the target. The presence of a visual context with cues of straight ahead enhanced pointing performance to the remembered location of central but not off-center targets. Thus, visual context provides strong visual cues of target position and the relationship of body position to target location. Without a visual context, egocentric cues provide sufficient input for accurate pointing to remembered targets.

Microencapsulation: A promising technique for controlled drug delivery.

PubMed

Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

2010-07-01

MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

Microencapsulation: A promising technique for controlled drug delivery

PubMed Central

Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

2010-01-01

Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

Recent Advances in Prostate Cancer Treatment and Drug Discovery.

PubMed

Nevedomskaya, Ekaterina; Baumgart, Simon J; Haendler, Bernard

2018-05-04

Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC). Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA) targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

Augmented virtuality for arthroscopic knee surgery.

PubMed

Li, John M; Bardana, Davide D; Stewart, A James

2011-01-01

This paper describes a computer system to visualize the location and alignment of an arthroscope using augmented virtuality. A 3D computer model of the patient's joint (from CT) is shown, along with a model of the tracked arthroscopic probe and the projection of the camera image onto the virtual joint. A user study, using plastic bones instead of live patients, was made to determine the effectiveness of this navigated display; the study showed that the navigated display improves target localization in novice residents.

Rapamycin: the cure for all that ails.

PubMed

Hasty, Paul

2010-02-01

Target of rapamycin (TOR) signaling stimulates cell growth by regulating protein synthesis in response to a variety of stimuli in a wide range of species and is inhibited by rapamycin, a naturally occurring antifungal compound produced by bacteria and discovered on Easter Island or in the local vernacular, Rapa Nui (rapamycin's namesake). Recently, rapamycin was shown to extend life span for mice, even when administered late in life, suggesting that inhibiting the mammalian TOR pathway may improve health span for people.

Analysis of calibration accuracy of cameras with different target sizes for large field of view

NASA Astrophysics Data System (ADS)

Zhang, Jin; Chai, Zhiwen; Long, Changyu; Deng, Huaxia; Ma, Mengchao; Zhong, Xiang; Yu, Huan

2018-03-01

Visual measurement plays an increasingly important role in the field o f aerospace, ship and machinery manufacturing. Camera calibration of large field-of-view is a critical part of visual measurement . For the issue a large scale target is difficult to be produced, and the precision can not to be guaranteed. While a small target has the advantage of produced of high precision, but only local optimal solutions can be obtained . Therefore, studying the most suitable ratio of the target size to the camera field of view to ensure the calibration precision requirement of the wide field-of-view is required. In this paper, the cameras are calibrated by a series of different dimensions of checkerboard calibration target s and round calibration targets, respectively. The ratios of the target size to the camera field-of-view are 9%, 18%, 27%, 36%, 45%, 54%, 63%, 72%, 81% and 90%. The target is placed in different positions in the camera field to obtain the camera parameters of different positions . Then, the distribution curves of the reprojection mean error of the feature points' restructure in different ratios are analyzed. The experimental data demonstrate that with the ratio of the target size to the camera field-of-view increas ing, the precision of calibration is accordingly improved, and the reprojection mean error changes slightly when the ratio is above 45%.

Rewiring the primary somatosensory cortex in carpal tunnel syndrome with acupuncture

PubMed Central

Maeda, Yumi; Kim, Hyungjun; Kettner, Norman; Kim, Jieun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Ong-Sutherland, Rebecca; Mezzacappa, Pia; Libby, Alexandra; Mawla, Ishtiaq; Morse, Leslie R.; Kaptchuk, Ted J.; Audette, Joseph

2017-01-01

Abstract Carpal tunnel syndrome is the most common entrapment neuropathy, affecting the median nerve at the wrist. Acupuncture is a minimally-invasive and conservative therapeutic option, and while rooted in a complex practice ritual, acupuncture overlaps significantly with many conventional peripherally-focused neuromodulatory therapies. However, the neurophysiological mechanisms by which acupuncture impacts accepted subjective/psychological and objective/physiological outcomes are not well understood. Eligible patients (n = 80, 65 female, age: 49.3 ± 8.6 years) were enrolled and randomized into three intervention arms: (i) verum electro-acupuncture ‘local’ to the more affected hand; (ii) verum electro-acupuncture at ‘distal’ body sites, near the ankle contralesional to the more affected hand; and (iii) local sham electro-acupuncture using non-penetrating placebo needles. Acupuncture therapy was provided for 16 sessions over 8 weeks. Boston Carpal Tunnel Syndrome Questionnaire assessed pain and paraesthesia symptoms at baseline, following therapy and at 3-month follow-up. Nerve conduction studies assessing median nerve sensory latency and brain imaging data were acquired at baseline and following therapy. Functional magnetic resonance imaging assessed somatotopy in the primary somatosensory cortex using vibrotactile stimulation over three digits (2, 3 and 5). While all three acupuncture interventions reduced symptom severity, verum (local and distal) acupuncture was superior to sham in producing improvements in neurophysiological outcomes, both local to the wrist (i.e. median sensory nerve conduction latency) and in the brain (i.e. digit 2/3 cortical separation distance). Moreover, greater improvement in second/third interdigit cortical separation distance following verum acupuncture predicted sustained improvements in symptom severity at 3-month follow-up. We further explored potential differential mechanisms of local versus distal acupuncture using diffusion tensor imaging of white matter microstructure adjacent to the primary somatosensory cortex. Compared to healthy adults (n = 34, 28 female, 49.7 ± 9.9 years old), patients with carpal tunnel syndrome demonstrated increased fractional anisotropy in several regions and, for these regions we found that improvement in median nerve latency was associated with reduction of fractional anisotropy near (i) contralesional hand area following verum, but not sham, acupuncture; (ii) ipsilesional hand area following local, but not distal or sham, acupuncture; and (iii) ipsilesional leg area following distal, but not local or sham, acupuncture. As these primary somatosensory cortex subregions are distinctly targeted by local versus distal acupuncture electrostimulation, acupuncture at local versus distal sites may improve median nerve function at the wrist by somatotopically distinct neuroplasticity in the primary somatosensory cortex following therapy. Our study further suggests that improvements in primary somatosensory cortex somatotopy can predict long-term clinical outcomes for carpal tunnel syndrome. PMID:28334999

Local-global interference is modulated by age, sex and anterior corpus callosum size

PubMed Central

Müller-Oehring, Eva M.; Schulte, Tilman; Raassi, Carla; Pfefferbaum, Adolf; Sullivan, Edith V.

2007-01-01

To identify attentional and neural mechanisms affecting global and local feature extraction, we devised a global-local hierarchical letter paradigm to test the hypothesis that aging reduces functional cerebral lateralization through corpus callosum (CC) degradation. Participants (37 men and women, 26–79 years) performed a task requiring global, local, or global+local attention and underwent structural MRI for CC measurement. Although reaction time (RT) slowed with age, all participants had faster RTs to local than global targets. This local precedence effect together with greater interference from incongruent local information and greater response conflict from local targets each correlated with older age and smaller callosal genu (anterior) areas. These findings support the hypothesis that the CC mediates lateralized local-global processes by inhibition of task-irrelevant information under selective attention conditions. Further, with advancing age smaller genu size leads to less robust inhibition, thereby reducing cerebral lateralization and permitting interference to influence processing. Sex was an additional modifier of interference, in that callosum-interference relationships were evident in women but not in men. Regardless of age, smaller splenium (posterior) areas correlated with less response facilitation from repetition priming of global targets in men, but with greater response facilitation from repetition priming of local targets in women. Our data indicate the following dissociation: Anterior callosal structure was associated with inhibitory processes (i.e., interference from incongruency and response conflict), which are vulnerable to the effects of age and sex, whereas posterior callosal structure was associated with facilitation processes from repetition priming dependent on sex and independent of age. PMID:17335783

Local-global interference is modulated by age, sex and anterior corpus callosum size.

PubMed

Müller-Oehring, Eva M; Schulte, Tilman; Raassi, Carla; Pfefferbaum, Adolf; Sullivan, Edith V

2007-04-20

To identify attentional and neural mechanisms affecting global and local feature extraction, we devised a global-local hierarchical letter paradigm to test the hypothesis that aging reduces functional cerebral lateralization through corpus callosum (CC) degradation. Participants (37 men and women, 26-79 years) performed a task requiring global, local, or global+local attention and underwent structural MRI for CC measurement. Although reaction time (RT) slowed with age, all participants had faster RTs to local than global targets. This local precedence effect together with greater interference from incongruent local information and greater response conflict from local targets each correlated with older age and smaller callosal genu (anterior) areas. These findings support the hypothesis that the CC mediates lateralized local-global processes by inhibition of task-irrelevant information under selective attention conditions. Further, with advancing age smaller genu size leads to less robust inhibition, thereby reducing cerebral lateralization and permitting interference to influence processing. Sex was an additional modifier of interference, in that callosum-interference relationships were evident in women but not in men. Regardless of age, smaller splenium (posterior) areas correlated with less response facilitation from repetition priming of global targets in men, but with greater response facilitation from repetition priming of local targets in women. Our data indicate the following dissociation: anterior callosal structure was associated with inhibitory processes (i.e., interference from incongruency and response conflict), which are vulnerable to the effects of age and sex, whereas posterior callosal structure was associated with facilitation processes from repetition priming dependent on sex and independent of age.

Paradigm shift in bacteriophage-mediated delivery of anticancer drugs: from targeted 'magic bullets' to self-navigated 'magic missiles'.

PubMed

Petrenko, Valery A; Gillespie, James W

2017-03-01

New phage-directed nanomedicines have emerged recently as a result of the in-depth study of the genetics and structure of filamentous phage and evolution of phage display and phage nanobiotechnology. This review focuses on the progress made in the development of the cancer-targeted nanomaterials and discusses the trends in using phage as a bioselectable molecular navigation system. Areas covered: The merging of phage display technologies with nanotechnology in recent years has proved promising in different areas of medicine and technology, such as medical diagnostics, molecular imaging, vaccine development and targeted drug/gene delivery, which is the focus of this review. The authors used data obtained from their research group and sourced using Science Citation Index (Web of Science) and NCBI PubMed search resources. Expert opinion: First attempts of adapting traditional concepts of direct targeting of tumor using phage-targeted nanomedicines has shown minimal improvements. With discovery and study of biological and technical barriers that prevent anti-tumor drug delivery, a paradigm shift from traditional drug targeting to nanomedicine navigation systems is required. The advanced bacteriophage-driven self-navigation systems are thought to overcome those barriers using more precise, localized phage selection methods, multi-targeting 'promiscuous' ligands and advanced multifunctional nanomedicine platforms.

Targeting the extracellular matrix of ovarian cancer using functionalized, drug loaded lyophilisomes.

PubMed

van der Steen, Sophieke C H A; Raavé, René; Langerak, Sjoerd; van Houdt, Laurens; van Duijnhoven, Sander M J; van Lith, Sanne A M; Massuger, Leon F A G; Daamen, Willeke F; Leenders, William P; van Kuppevelt, Toin H

2017-04-01

Epithelial ovarian cancer is characterized by a high mortality rate and is in need for novel therapeutic avenues to improve patient outcome. The tumor's extracellular matrix ("stroma") offers new possibilities for targeted drug-delivery. Recently we identified highly sulfated chondroitin sulfate (CS-E) as a component abundantly present in the ovarian cancer extracellular matrix, and as a novel target for anti-cancer therapy. Here, we report on the functionalization of drug-loaded lyophilisomes (albumin-based biocapsules) to specifically target the stroma of ovarian carcinomas with the potential to eliminate cancer cells. To achieve specific targeting, we conjugated single chain antibodies reactive with CS-E to lyophilisomes using a two-step approach comprising sortase-mediated ligation and bioorthogonal click chemistry. Antibody-functionalized lyophilisomes specifically targeted the ovarian cancer stroma through CS-E. In a CS-E rich micro-environment in vitro lyophilisomes induced cell death by extracellular release of doxorubicin which localized to the nucleus. Immunohistochemistry identified CS-E rich stroma in a variety of solid tumors other than ovarian cancer, including breast, lung and colon cancer indicating the potential versatility of matrix therapy and the use of highly sulfated chondroitin sulfates in cancer stroma as a micro-environmental hook for targeted drug delivery. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Targeting the 5T4 oncofetal glycoprotein with an antibody drug conjugate (A1mcMMAF) improves survival in patient-derived xenograft models of acute lymphoblastic leukemia.

PubMed

McGinn, Owen J; Krishnan, Shekhar; Bourquin, Jean-Pierre; Sapra, Puja; Dempsey, Clare; Saha, Vaskar; Stern, Peter L

2017-06-01

Outcome in childhood acute lymphoblastic leukemia is prognosticated from levels of minimal residual disease after remission induction therapy. Higher levels of minimal residual disease are associated with inferior results even with intensification of therapy, thus suggesting that identification and targeting of minimal residual disease cells could be a therapeutic strategy. Here we identify high expression of 5T4 in subclonal populations of patient-derived xenografts from patients with high, post-induction levels of minimal residual disease. 5T4-positive cells showed preferential ability to overcome the NOD- scid IL2Rγ null mouse xenograft barrier, migrated in vitro on a CXCL12 gradient, preferentially localized to bone marrow in vivo and displayed the ability to reconstitute the original clonal composition on limited dilution engraftment. Treatment with A1mcMMAF (a 5T4-antibody drug conjugate) significantly improved survival without overt toxicity in mice engrafted with a 5T4-positive acute lymphoblastic leukemia cell line. Mice engrafted with 5T4-positive patient-derived xenograft cells were treated with combination chemotherapy or dexamethasone alone and then given A1mcMMAF in the minimal residual disease setting. Combination chemotherapy was toxic to NOD- scid IL2Rγ null mice. While dexamethasone or A1mcMMAF alone improved outcomes, the sequential administration of dexamethasone and A1mcMMAF significantly improved survival ( P =0.0006) over either monotherapy. These data show that specifically targeting minimal residual disease cells improved outcomes and support further investigation of A1mcMMAF in patients with high-risk B-cell precursor acute lymphoblastic leukemia identified by 5T4 expression at diagnosis. Copyright© Ferrata Storti Foundation.

Targeting the 5T4 oncofetal glycoprotein with an antibody drug conjugate (A1mcMMAF) improves survival in patient-derived xenograft models of acute lymphoblastic leukemia

PubMed Central

McGinn, Owen J.; Krishnan, Shekhar; Bourquin, Jean-Pierre; Sapra, Puja; Dempsey, Clare; Saha, Vaskar; Stern, Peter L.

2017-01-01

Outcome in childhood acute lymphoblastic leukemia is prognosticated from levels of minimal residual disease after remission induction therapy. Higher levels of minimal residual disease are associated with inferior results even with intensification of therapy, thus suggesting that identification and targeting of minimal residual disease cells could be a therapeutic strategy. Here we identify high expression of 5T4 in subclonal populations of patient-derived xenografts from patients with high, post-induction levels of minimal residual disease. 5T4-positive cells showed preferential ability to overcome the NOD-scidIL2Rγnull mouse xenograft barrier, migrated in vitro on a CXCL12 gradient, preferentially localized to bone marrow in vivo and displayed the ability to reconstitute the original clonal composition on limited dilution engraftment. Treatment with A1mcMMAF (a 5T4-antibody drug conjugate) significantly improved survival without overt toxicity in mice engrafted with a 5T4-positive acute lymphoblastic leukemia cell line. Mice engrafted with 5T4-positive patient-derived xenograft cells were treated with combination chemotherapy or dexamethasone alone and then given A1mcMMAF in the minimal residual disease setting. Combination chemotherapy was toxic to NOD-scidIL2Rγnull mice. While dexamethasone or A1mcMMAF alone improved outcomes, the sequential administration of dexamethasone and A1mcMMAF significantly improved survival (P=0.0006) over either monotherapy. These data show that specifically targeting minimal residual disease cells improved outcomes and support further investigation of A1mcMMAF in patients with high-risk B-cell precursor acute lymphoblastic leukemia identified by 5T4 expression at diagnosis. PMID:28341731

An evaluation of talker localization based on direction of arrival estimation and statistical sound source identification

NASA Astrophysics Data System (ADS)

Nishiura, Takanobu; Nakamura, Satoshi

2002-11-01

It is very important to capture distant-talking speech for a hands-free speech interface with high quality. A microphone array is an ideal candidate for this purpose. However, this approach requires localizing the target talker. Conventional talker localization algorithms in multiple sound source environments not only have difficulty localizing the multiple sound sources accurately, but also have difficulty localizing the target talker among known multiple sound source positions. To cope with these problems, we propose a new talker localization algorithm consisting of two algorithms. One is DOA (direction of arrival) estimation algorithm for multiple sound source localization based on CSP (cross-power spectrum phase) coefficient addition method. The other is statistical sound source identification algorithm based on GMM (Gaussian mixture model) for localizing the target talker position among localized multiple sound sources. In this paper, we particularly focus on the talker localization performance based on the combination of these two algorithms with a microphone array. We conducted evaluation experiments in real noisy reverberant environments. As a result, we confirmed that multiple sound signals can be identified accurately between ''speech'' or ''non-speech'' by the proposed algorithm. [Work supported by ATR, and MEXT of Japan.

Improving dementia diagnosis and management in primary care: a cohort study of the impact of a training and support program on physician competency, practice patterns, and community linkages.

PubMed

Lathren, Christine R; Sloane, Philip D; Hoyle, Joseph D; Zimmerman, Sheryl; Kaufer, Daniel I

2013-12-10

Primary care physicians routinely provide dementia care, but may lack the clinical skills and awareness of available resources to provide optimal care. We conducted a community-based pilot dementia training intervention designed to both improve clinical competency and increase utilization of local dementia care services. Physicians (N = 29) and affiliated staff (N = 24) participated in a one-day training program on dementia screening, diagnosis and management that included direct engagement with local support service providers. Questionnaires about their dementia care competency and referral patterns were completed before and 6 months after the training intervention. Physicians reported significantly higher overall confidence in their dementia care competency 6 months post-training compared to pre-training. The largest reported improvements were in their ability to educate patients and caregivers about dementia and making appropriate referrals to community care services. Participants also reported markedly increased use of cognitive screening tools in providing care. Community service providers recorded approximately 160 physician-initiated referrals over a 2 year-period post-training, compared to few beforehand. Combining a targeted physician practice-based educational intervention with community service engagement improves dementia care competency in clinicians and promotes linkages between clinical and community dementia care providers.

Trial of a Novel Intervention to Improve Multiple Food Hygiene Behaviors in Nepal

PubMed Central

Gautam, Om Prasad; Schmidt, Wolf-Peter; Cairncross, Sandy; Cavill, Sue; Curtis, Valerie

2017-01-01

In this study, we report on the results of a trial of an intervention to improve five food hygiene behaviors among mothers of young children in rural Nepal. This novel intervention targeted five behaviors; cleanliness of serving utensils, handwashing with soap before feeding, proper storage of cooked food, and thorough reheating and water treatment. Based on formative research and a creative process using the Behavior-Centered Design approach, an innovative intervention package was designed and delivered over a period of 3 months. The intervention activities included local rallies, games, rewards, storytelling, drama, competitions linking with emotional drivers of behavior, and “kitchen makeovers” to disrupt behavior settings. The effect of the package on behavior was evaluated via a cluster-randomized before–after study in four villages with four villages serving as controls. The primary outcome was the difference in the mean cluster level proportions of mothers directly observed practicing all five food hygiene behaviors. The five targeted food hygiene behaviors were rare at baseline (composite performance of all five behaviors in intervention 1% [standard deviation (SD) = 2%] and in control groups 2% [SD = 2%]). Six weeks after the intervention, the target behaviors were more common in the intervention than in the control group (43% [SD = 14%] versus 2% [SD = 2%], P = 0.02) during follow-up. The intervention appeared to be equally effective in improving all five behaviors in all intervention clusters. This study shows that a theory-driven, systematic approach employing emotional motivators and modifying behavior settings was capable of substantially improving multiple food hygiene behaviors in Nepal. PMID:28719285

Trial of a Novel Intervention to Improve Multiple Food Hygiene Behaviors in Nepal.

PubMed

Gautam, Om Prasad; Schmidt, Wolf-Peter; Cairncross, Sandy; Cavill, Sue; Curtis, Valerie

2017-06-01

AbstractIn this study, we report on the results of a trial of an intervention to improve five food hygiene behaviors among mothers of young children in rural Nepal. This novel intervention targeted five behaviors; cleanliness of serving utensils, handwashing with soap before feeding, proper storage of cooked food, and thorough reheating and water treatment. Based on formative research and a creative process using the Behavior-Centered Design approach, an innovative intervention package was designed and delivered over a period of 3 months. The intervention activities included local rallies, games, rewards, storytelling, drama, competitions linking with emotional drivers of behavior, and "kitchen makeovers" to disrupt behavior settings. The effect of the package on behavior was evaluated via a cluster-randomized before-after study in four villages with four villages serving as controls. The primary outcome was the difference in the mean cluster level proportions of mothers directly observed practicing all five food hygiene behaviors. The five targeted food hygiene behaviors were rare at baseline (composite performance of all five behaviors in intervention 1% [standard deviation (SD) = 2%] and in control groups 2% [SD = 2%]). Six weeks after the intervention, the target behaviors were more common in the intervention than in the control group (43% [SD = 14%] versus 2% [SD = 2%], P = 0.02) during follow-up. The intervention appeared to be equally effective in improving all five behaviors in all intervention clusters. This study shows that a theory-driven, systematic approach employing emotional motivators and modifying behavior settings was capable of substantially improving multiple food hygiene behaviors in Nepal.

Extracorporeal adsorption therapy: A Method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nemecek, Eneida R.; Green, Damian J.; Fisher, Darrell R.

2008-04-01

Many investigators have demonstrated the ability to treat hematologic malignancies with radiolabeled monoclonal antibodies targeting hematopoietic antigens such as anti-CD20 and anti-CD45. [1-5] Although the remission rates achieved with radioimmunotherapy (RIT) are relatively high, many patients subsequently relapse presumably due to suboptimal delivery of enough radiation to eradicate the malignancy. The dose-response of leukemia and lymphoma to radiation has been proven. Substantial amounts of radiation can be delivered by RIT if followed by hematopoietic cell transplantation to rescue the bone marrow from myeloablation.[ref] However, the maximum dose of RIT that can be used is still limited by toxicity to normalmore » tissues affected by nonspecific delivery of radiation. Efforts to improve RIT focus on improving the therapeutic ratios of radiation in target versus non-target tissues by removing the fraction of radioisotope that fails to bind to target tissues and circulates freely in the bloodstream perfusing non-target tissues. Our group and others have explored several alternatives for removal of unbound circulating antibody. [refs] One such method, extracorporeal adsorption therapy (ECAT) consists of removing unbound antibody by a method similar to plasmapheresis after critical circulation time and distribution of antibody into target tissues have been achieved. Preclinical studies of ECAT in murine xenograft models demonstrated significant improvement in therapeutic ratios of radioactivity. Chen and colleagues demonstrated that a 2-hour ECAT procedure could remove 40 to 70% of the radioactivity from liver, lung and spleen. [ref] Although isotope concentration in the tumor was initially unaffected, a 50% decrease was noted approximately 36 hours after the procedure. This approach was also evaluated in a limited phase I pilot study of patients with refractory B-cell lymphoma. [ref] After radiographic confirmation of tumor localization of a test dose of anti-CD20 antibody labeled with indium-111 (111In), seven patients received RIT with anti-CD20 antibody labeled with indium-111 for biokinetics and dosimetry, and therapeutic doses of antibody labeled with yttrium-90 (90Y). Performing the ECAT procedure at a rate that such that one blood volume per hour were circulated for 3 hours, resulted in mean radioactivity depletion of 96% in whole blood, 49% in whole body 49%, 62% in the lungs and 40% in liver and kidneys. There was no sufficient data to determine whether there was an improvement in the relative delivery of radiation to the tumor compared to normal organs by performing ECAT, but pharmacokinetic modeling studies suggested a potential therapeutic advantage using this approach. [refs] To evaluate the potential therapeutic advantages of ECAT, we performed biodistribution studies in nonhuman primates comparing the therapeutic ratios of radiation delivered using this approach to those delivered by conventional RIT alone. In addition, we evaluated lutetium-177 (177Lu) as an alternative isotope to optimize the delivery of RIT by improving the therapeutic index (target to non-target ratio)« less

Best practice wound care.

PubMed

O'Brien, Melissa L; Lawton, Joanna E; Conn, Chris R; Ganley, Helen E

2011-04-01

This article describes the barriers, changes and achievements related to implementing one element of a wound care programme being best practice care. With the absence of a coordinated approach to wound care, clinical practice within our Area Health Service (AHS) was diverse, inconsistent and sometimes outdated. This was costly and harmful, leading to overuse of unhelpful care, underuse of effective care and errors in execution. The major aim was to improve the outcomes and quality of life for patients with wound care problems within our community. A collaborative across ten sites/services developed, implemented and evaluated policies and guidelines based on evidence-based bundles of care. Key barriers were local resistance and lack of experience in implementing structural and cultural changes. This was addressed by appointing a wound care programme manager, commissioning of a strategic oversight committee and local wound care committees. The techniques of spread and adoption were used, with early adopters making changes observable and allowing local adaption of guidelines, where appropriate. Deployment and improvement results varied across the sites, ranging from activity but no changes in practice to modest improvement in practice. Evaluating implementation of the leg ulcer guideline as an exemplar, it was demonstrated that there was a statistically significant improvement in overall compliance from 26% to 84%. However, only 7·7% of patients received all interventions to which they were entitled. Compliance with the eight individual interventions of the bundle ranged from 26% to 84%. Generic performance was evaluated against the wound assessment, treatment and evaluation plan with an average compliance of 70%. Early results identified that 20% of wounds were healed within the target of 10 days. As more standardised process are implemented, clinical outcomes should continue to improve and costs decrease. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Ablation as targeted perturbation to rewire communication network of persistent atrial fibrillation

PubMed Central

Tao, Susumu; Way, Samuel F.; Garland, Joshua; Chrispin, Jonathan; Ciuffo, Luisa A.; Balouch, Muhammad A.; Nazarian, Saman; Spragg, David D.; Marine, Joseph E.; Berger, Ronald D.; Calkins, Hugh

2017-01-01

Persistent atrial fibrillation (AF) can be viewed as disintegrated patterns of information transmission by action potential across the communication network consisting of nodes linked by functional connectivity. To test the hypothesis that ablation of persistent AF is associated with improvement in both local and global connectivity within the communication networks, we analyzed multi-electrode basket catheter electrograms of 22 consecutive patients (63.5 ± 9.7 years, 78% male) during persistent AF before and after the focal impulse and rotor modulation-guided ablation. Eight patients (36%) developed recurrence within 6 months after ablation. We defined communication networks of AF by nodes (cardiac tissue adjacent to each electrode) and edges (mutual information between pairs of nodes). To evaluate patient-specific parameters of communication, thresholds of mutual information were applied to preserve 10% to 30% of the strongest edges. There was no significant difference in network parameters between both atria at baseline. Ablation effectively rewired the communication network of persistent AF to improve the overall connectivity. In addition, successful ablation improved local connectivity by increasing the average clustering coefficient, and also improved global connectivity by decreasing the characteristic path length. As a result, successful ablation improved the efficiency and robustness of the communication network by increasing the small-world index. These changes were not observed in patients with AF recurrence. Furthermore, a significant increase in the small-world index after ablation was associated with synchronization of the rhythm by acute AF termination. In conclusion, successful ablation rewires communication networks during persistent AF, making it more robust, efficient, and easier to synchronize. Quantitative analysis of communication networks provides not only a mechanistic insight that AF may be sustained by spatially localized sources and global connectivity, but also patient-specific metrics that could serve as a valid endpoint for therapeutic interventions. PMID:28678805

The efficacy of targeted health agents education to reduce the duration of untreated psychosis in a rural population.

PubMed

Padilla, Eduardo; Molina, Juan; Kamis, Danielle; Calvo, Maria; Stratton, Lee; Strejilevich, Sergio; Aleman, Gabriela Gonzalez; Guerrero, Gonzalo; Bourdieu, Mercedes; Conesa, Horacio A; Escobar, Javier I; de Erausquin, Gabriel A

2015-02-01

The duration of untreated psychosis (DUP) is a key determinant in the severity of symptoms in patients with schizophrenia. DUP is a modifiable factor that if reduced can improve patient outcome and treatment response. We sought to decrease DUP in rural Argentina by instituting annual training of local health agents to better identify signs of mental illness and offer earlier intervention. DUP was estimated using Schedules of Clinical Assessment in Neuropsychiatry (SCAN). Ongoing training was correlated with a reduction in DUP. Reducing DUP through better screening can decrease the psychosocial burden of disease and improve the trajectory of psychosis. Copyright © 2014 Elsevier B.V. All rights reserved.

[Determinants of dengue transmission in Veracruz: an ecological approach to its control].

PubMed

Escobar-Mesa, Javier; Gómez-Dantés, Héctor

2003-01-01

To assess the ecological, social, and demographic factors associated with the transmission of dengue virus infection in Veracruz, Mexico, and to identify risk areas to target control measures. This ecological study included data for 1,249 localities within the 11 Health Jurisdictions of the State of Veracruz, Mexico, for the 1995-1998 period. The following data were collected for each locality: total number of cases per year, population by sex, number of households, provision of public services, altitude, latitude, longitude, and deprivation index. Dengue transmission was registered in 17% of the localities in the State; 70% of the cases were concentrated in only 6% of the localities. Recurrent localities were urban centers with adequate availability of public services and low deprivation indices. Dengue transmission was detected in rural areas, but it was not common. The average number of cases differed according to the size of the locality and the number of years dengue was reported. A population threshold to maintain transmission was found. Recurrent localities concentrating 70% of dengue fever cases were identified, as well as the ecological and demographic factors associated with dengue transmission. The risk stratification approach to dengue transmission may improve control and prevention of this disease in high-risk areas.

SU-E-T-669: Radiosurgery Failure for Trigeminal Neuralgia: A Study of Radiographic Spatial Fidelity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howe, J; Spalding, A

Purpose: Management of Trigeminal Neuralgia with radiosurgery is well established, but often met with limited success. Recent advancements in imaging afford improvements in target localization for radiosurgery. Methods: A Trigeminal Neuralgia radiosurgery specific protocol was established for MR enhancement of the trigeminal nerve using a CISS scan with slice spacing of 0.7mm. Computed Tomography simulation was performed using axial slices on a 40 slice CT with slice spacing of 0.6mm. These datasets were registered using a mutual information algorithm and localized in a stereotactic coordinate system. Image registration between the MR and CT was evaluated for each patient by amore » Medical Physicist to ensure accuracy. The dorsal root entry zone target was defined on the CISS MR by a Neurosurgeon and dose calculations performed on the localized CT. Treatment plans were reviewed and approved by a Radiation Oncologist and Neurosurgeon. Image guided radiosurgery was delivered using positioning tolerance of 0.5mm and 1°. Eight patients with Trigeminal Neuralgia were treated with this protocol. Results: Seven patients reported a favorable response to treatment with average Barrow Neurological Index pain score of four before treatment and one following treatment. Only one patient had a BNI>1 following treatment and review of the treatment plan revealed that the CISS MR was registered to the CT via a low resolution (5mm slice spacing) T2 MR. All other patients had CISS MR registered directly with the localized CT. This patient was retreated 6 months later using direct registration between CISS MR and localized CT and subsequently responded to treatment with a BNI of one. Conclusion: Frameless radiosurgery offers an effective solution to Trigeminal Neuralgia management provided appropriate technology and imaging protocols (utilizing submillimeter imaging) are established and maintained.« less

Agent Collaborative Target Localization and Classification in Wireless Sensor Networks

PubMed Central

Wang, Xue; Bi, Dao-wei; Ding, Liang; Wang, Sheng

2007-01-01

Wireless sensor networks (WSNs) are autonomous networks that have been frequently deployed to collaboratively perform target localization and classification tasks. Their autonomous and collaborative features resemble the characteristics of agents. Such similarities inspire the development of heterogeneous agent architecture for WSN in this paper. The proposed agent architecture views WSN as multi-agent systems and mobile agents are employed to reduce in-network communication. According to the architecture, an energy based acoustic localization algorithm is proposed. In localization, estimate of target location is obtained by steepest descent search. The search algorithm adapts to measurement environments by dynamically adjusting its termination condition. With the agent architecture, target classification is accomplished by distributed support vector machine (SVM). Mobile agents are employed for feature extraction and distributed SVM learning to reduce communication load. Desirable learning performance is guaranteed by combining support vectors and convex hull vectors. Fusion algorithms are designed to merge SVM classification decisions made from various modalities. Real world experiments with MICAz sensor nodes are conducted for vehicle localization and classification. Experimental results show the proposed agent architecture remarkably facilitates WSN designs and algorithm implementation. The localization and classification algorithms also prove to be accurate and energy efficient.

Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer.

PubMed

Skinner, Heath D; Giri, Uma; Yang, Liang; Woo, Sang Hyeok; Story, Michael D; Pickering, Curtis R; Byers, Lauren A; Williams, Michelle D; El-Naggar, Adel; Wang, Jing; Diao, Lixia; Shen, Li; Fan, You Hong; Molkentine, David P; Beadle, Beth M; Meyn, Raymond E; Myers, Jeffrey N; Heymach, John V

2016-09-15

Head and neck squamous cell carcinoma (HNSCC) is commonly treated with radiotherapy, and local failure after treatment remains the major cause of disease-related mortality. To date, human papillomavirus (HPV) is the only known clinically validated, targetable biomarkers of response to radiation in HNSCC. We performed proteomic and transcriptomic analysis of targetable biomarkers of radioresistance in HPV-negative HNSCC cell lines in vitro, and tested whether pharmacologic blockade of candidate biomarkers sensitized cells to radiotherapy. Candidate biomarkers were then investigated in several independent cohorts of patients with HNSCC. Increased expression of several targets was associated with radioresistance, including FGFR, ERK1, EGFR, and focal adhesion kinase (FAK), also known as PTK2. Chemical inhibition of PTK2/FAK, but not FGFR, led to significant radiosensitization with increased G2-M arrest and potentiated DNA damage. PTK2/FAK overexpression was associated with gene amplification in HPV-negative HNSCC cell lines and clinical tumors. In two independent cohorts of patients with locally advanced HPV-negative HNSCC, PTK2/FAK amplification was highly associated with poorer disease-free survival (DFS; P = 0.012 and 0.034). PTK2/FAK mRNA expression was also associated with worse DFS (P = 0.03). Moreover, both PTK2/FAK mRNA (P = 0.021) and copy number (P = 0.063) were associated with DFS in the Head and Neck Cancer subgroup of The Cancer Genome Atlas. Proteomic analysis identified PTK2/FAK overexpression is a biomarker of radioresistance in locally advanced HNSCC, and PTK2/FAK inhibition radiosensitized HNSCC cells. Combinations of PTK2/FAK inhibition with radiotherapy merit further evaluation as a therapeutic strategy for improving local control in HPV-negative HNSCC. Clin Cancer Res; 22(18); 4643-50. ©2016 AACR. ©2016 American Association for Cancer Research.

In vitro/in vivo characterization of nanoemulsion formulation of metronidazole with improved skin targeting and anti-rosacea properties.

PubMed

Yu, Meng; Ma, Huixian; Lei, Mingzhu; Li, Nan; Tan, Fengping

2014-09-01

Topical skin treatment was limited due to the lack of suitable delivery system with significant cutaneous localization and systemic safety. The aim of this study was to develop and optimize a nanoemulsion (NE) to enhance targeting localization of metronidazole (MTZ) in skin layers. In vitro studies were used to optimize NE formulations, and a series of experiments were carried in vitro and in vivo to validate the therapeutic efficacy of MTZ-loaded optimal NE. NE type selection and D-optimal design study were applied to optimize NE formulation with maximum skin retention and minimum skin penetration. Three formulation variables: Oil X1 (Labrafil), Smix X2 (a mixture of Cremophor EL/Tetraethylene glycol, 2:1 w/w) and water X3 were included in D-design. The system was assessed for skin retention Y1, cumulative MTZ amount after 24 h Y2 and droplet size Y3. Following optimization, the values of formulation components (X1, X2 and X3) were 4.13%, 16.42% and 79.45%, respectively. The optimized NE was assessed for viscosity, droplet size, morphological study and in vitro permeation in pig skin. Distributions of MTZ were validated by confocal laser scanning microscopy (CLSM). Active agent of NE transferred into deeper skin and localized in epidermal/dermal layers after 24 h, which showed significant advantages of the optimal NE over Gel. The skin targeting localization and minimal systemic escape of optimal NE was further proved by in vivo study on rat skin. Current in vitro-in vivo correlation (IVIVC) enabled the prediction of pharmacokinetic profile of MTZ from in vitro permeation results. Further, the in vivo anti-rosacea efficacy of optimal formulation was investigated by pharmacodynamics study on mice ear. Copyright © 2014 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koay, Eugene J.; Lege, David; Mohan, Radhe

Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in termsmore » of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans.« less

Advances in radioguided surgery in oncology.

PubMed

Valdés Olmos, Renato A; Vidal-Sicart, Sergi; Manca, Gianpiero; Mariani, Giuliano; León-Ramírez, Luisa F; Rubello, Domenico; Giammarile, Francesco

2017-09-01

The sentinel lymph node (SLN) biopsy is probably the most well-known radioguided technique in surgical oncology. Today SLN biopsy reduces the morbidity associated with lymphadenectomy and increases the identification rate of occult lymphatic metastases by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. These advantages may result in a change in clinical management both in melanoma and breast cancer patients. The SLN evaluation by pathology currently implies tumor burden stratification for further prognostic information. The concept of SLN biopsy includes pre-surgical lymphoscintigraphy as a "roadmap" to guide the surgeon toward the SLNs and to localize unpredictable lymphatic drainage patterns. In addition to planar images, SPECT/CT improves SLN detection, especially in sites closer to the injection site, providing anatomic landmarks which are helpful in localizing SLNs in difficult to interpret studies. The use of intraoperative imaging devices allows a better surgical approach and SLN localization. Several studies report the value of such devices for excision of additional sentinel nodes and for monitoring the whole procedure. The combination of preoperative imaging and radioguided localization constitutes the basis for a whole spectrum of basic and advanced nuclear medicine procedures, which recently have been encompassed under the term "guided intraoperative scintigraphic tumor targeting" (GOSTT). Excepting SLN biopsy, GOSTT includes procedures based on the detection of target lesions with visible uptake of tumor-seeking radiotracers on SPECT/CT or PET/CT enabling their subsequent radioguided excisional biopsy for diagnostic of therapeutic purposes. The incorporation of new PET-tracers into nuclear medicine has reinforced this field delineating new strategies for radioguided excision. In cases with insufficient lesion uptake after systemic radiotracer administration, intralesional injection of a tracer without migration may enable subsequent excision of the targeted tissue. This approach has been helpful in non-palpable breast cancer and in solitary pulmonary nodules. The introduction of allied technologies like fluorescence constitutes a recent advance aimed to refine the search for SLNs and tracer-avid lesions in the operation theatre in combination with radioguidance.

Targeted Degradation of Proteins Localized in Subcellular Compartments by Hybrid Small Molecules.

PubMed

Okuhira, Keiichiro; Shoda, Takuji; Omura, Risa; Ohoka, Nobumichi; Hattori, Takayuki; Shibata, Norihito; Demizu, Yosuke; Sugihara, Ryo; Ichino, Asato; Kawahara, Haruka; Itoh, Yukihiro; Ishikawa, Minoru; Hashimoto, Yuichi; Kurihara, Masaaki; Itoh, Susumu; Saito, Hiroyuki; Naito, Mikihiko

2017-03-01

Development of novel small molecules that selectively degrade pathogenic proteins would provide an important advance in targeted therapy. Recently, we have devised a series of hybrid small molecules named SNIPER (specific and nongenetic IAP-dependent protein ERaser) that induces the degradation of target proteins via the ubiquitin-proteasome system. To understand the localization of proteins that can be targeted by this protein knockdown technology, we examined whether SNIPER molecules are able to induce degradation of cellular retinoic acid binding protein II (CRABP-II) proteins localized in subcellular compartments of cells. CRABP-II is genetically fused with subcellular localization signals, and they are expressed in the cells. SNIPER(CRABP) with different IAP-ligands, SNIPER(CRABP)-4 with bestatin and SNIPER(CRABP)-11 with MV1 compound, induce the proteasomal degradation of wild-type (WT), cytosolic, nuclear, and membrane-localized CRABP-II proteins, whereas only SNIPER(CRABP)-11 displayed degradation activity toward the mitochondrial CRABP-II protein. The small interfering RNA-mediated silencing of cIAP1 expression attenuated the knockdown activity of SNIPER(CRABP) against WT and cytosolic CRABP-II proteins, indicating that cIAP1 is the E3 ligase responsible for degradation of these proteins. Against membrane-localized CRABP-II protein, cIAP1 is also a primary E3 ligase in the cells, but another E3 ligase distinct from cIAP2 and X-linked inhibitor of apoptosis protein (XIAP) could also be involved in the SNIPER(CRABP)-11-induced degradation. However, for the degradation of nuclear and mitochondrial CRABP-II proteins, E3 ligases other than cIAP1, cIAP2, and XIAP play a role in the SNIPER-mediated protein knockdown. These results indicate that SNIPER can target cytosolic, nuclear, membrane-localized, and mitochondrial proteins for degradation, but the responsible E3 ligase is different, depending on the localization of the target protein. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Nanotechnology applications in thoracic surgery

PubMed Central

Hofferberth, Sophie C.; Grinstaff, Mark W.; Colson, Yolonda L.

2016-01-01

Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of ‘theranostic’ multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future. PMID:26843431

Cone-beam x-ray luminescence computed tomography based on x-ray absorption dosage

NASA Astrophysics Data System (ADS)

Liu, Tianshuai; Rong, Junyan; Gao, Peng; Zhang, Wenli; Liu, Wenlei; Zhang, Yuanke; Lu, Hongbing

2018-02-01

With the advances of x-ray excitable nanophosphors, x-ray luminescence computed tomography (XLCT) has become a promising hybrid imaging modality. In particular, a cone-beam XLCT (CB-XLCT) system has demonstrated its potential in in vivo imaging with the advantage of fast imaging speed over other XLCT systems. Currently, the imaging models of most XLCT systems assume that nanophosphors emit light based on the intensity distribution of x-ray within the object, not completely reflecting the nature of the x-ray excitation process. To improve the imaging quality of CB-XLCT, an imaging model that adopts an excitation model of nanophosphors based on x-ray absorption dosage is proposed in this study. To solve the ill-posed inverse problem, a reconstruction algorithm that combines the adaptive Tikhonov regularization method with the imaging model is implemented for CB-XLCT reconstruction. Numerical simulations and phantom experiments indicate that compared with the traditional forward model based on x-ray intensity, the proposed dose-based model could improve the image quality of CB-XLCT significantly in terms of target shape, localization accuracy, and image contrast. In addition, the proposed model behaves better in distinguishing closer targets, demonstrating its advantage in improving spatial resolution.

X-ray opacity measurements in mid-Z dense plasmas with a new target design of indirect heating

NASA Astrophysics Data System (ADS)

Dozières, M.; Thais, F.; Bastiani-Ceccotti, S.; Blenski, T.; Fariaut, J.; Fölsner, W.; Gilleron, F.; Khaghani, D.; Pain, J.-C.; Reverdin, C.; Rosmej, F.; Silvert, V.; Soullié, G.; Villette, B.

2015-12-01

X-ray transmission spectra of copper, nickel and aluminum laser produced plasmas were measured at the LULI2000 laser facility with an improved target design of indirect heating. Measurements were performed in plasmas close to local thermodynamic equilibrium at temperatures around 25 eV and densities between 10-3g/cm3 and 10-2 g/cm3. This improved design provides several advantages, which are discussed in this paper. The sample is a thin foil of mid-Z material inserted between two gold cavities heated by two 300J, 2ω, nanosecond laser beams. A third laser beam irradiates a gold foil to create a spectrally continuous X-ray source (backlight) used to probe the sample. We investigate 2p-3d absorption structures in Ni and Cu plasmas as well as 1s-2p transitions in an additional Al plasma layer to infer the in-situ plasma temperature. Geometric and hydrodynamic calculations indicate that the improved geometry reduces spatial gradients during the transmission measurements. Experimental absorption spectra are in good agreement with calculations from the hybrid atomic physics code SCO-RCG.

Image-Guided Radiation Therapy: the potential for imaging science research to improve cancer treatment outcomes

NASA Astrophysics Data System (ADS)

Williamson, Jeffrey

2008-03-01

The role of medical imaging in the planning and delivery of radiation therapy (RT) is rapidly expanding. This is being driven by two developments: Image-guided radiation therapy (IGRT) and biological image-based planning (BIBP). IGRT is the systematic use of serial treatment-position imaging to improve geometric targeting accuracy and/or to refine target definition. The enabling technology is the integration of high-performance three-dimensional (3D) imaging systems, e.g., onboard kilovoltage x-ray cone-beam CT, into RT delivery systems. IGRT seeks to adapt the patient's treatment to weekly, daily, or even real-time changes in organ position and shape. BIBP uses non-anatomic imaging (PET, MR spectroscopy, functional MR, etc.) to visualize abnormal tissue biology (angiogenesis, proliferation, metabolism, etc.) leading to more accurate clinical target volume (CTV) delineation and more accurate targeting of high doses to tissue with the highest tumor cell burden. In both cases, the goal is to reduce both systematic and random tissue localization errors (2-5 mm for conventional RT) conformality so that planning target volume (PTV) margins (varying from 8 to 20 mm in conventional RT) used to ensure target volume coverage in the presence of geometric error, can be substantially reduced. Reduced PTV expansion allows more conformal treatment of the target volume, increased avoidance of normal tissue and potential for safe delivery of more aggressive dose regimens. This presentation will focus on the imaging science challenges posed by the IGRT and BIBP. These issues include: Development of robust and accurate nonrigid image-registration (NIR) tools: Extracting locally nonlinear mappings that relate, voxel-by-voxel, one 3D anatomic representation of the patient to differently deformed anatomies acquired at different time points, is essential if IGRT is to move beyond simple translational treatment plan adaptations. NIR is needed to map segmented and labeled anatomy from the pretreatment planning images to each daily treatment position image and to deformably map delivered dose distributions computed on each time instance of deformed anatomy, back to the reference 3D anatomy. Because biological imaging must be performed offline, NIR is needed to deformably map these images onto CT images acquired during treatment. Reducing target and organ contouring errors: As IGRT significantly reduces impact of differences between planning and treatment anatomy, RT targeting accuracy becomes increasingly dominated by the remaining systematic treatment-preparation errors, chiefly error in delineating the clinical target volume (CTV) and organs-at-risk. These delineation errors range from 1 mm to 5 mm. No single solution to this problem exists. For BIBP, a better understanding of tumor cell density vs. signal intensity is required. For anatomic CT imaging, improved image reconstruction techniques that improve contrast-to-noise ratio, reduce artifacts due to limited projection data, and incorporate prior information are promising. More sophisticated alternatives to the current concept fixed boundary anatomic structures are needed, e.g., probabilistic CTV representations that incorporate delineation uncertainties. Quantifying four-dimensional (4D) anatomy: For adaptive treatment planning to produce an optimal time sequence of delivery parameters, a 4D anatomic representation, the spatial trajectory through time of each tissue voxel, is needed. One approach is to use sequences of deformation vector fields derived by non-rigidly registering each treatment image to the reference planning CT. One problem to be solved is prediction of future deformed anatomies from past behavior so that time delays inherent in any adaptive replanning feedback loop can be overcome. Another unsolved problem is quantification 4D anatomy uncertainties and how to incorporate such uncertainties into the treatment planning process to avoid geometric ``miss'' of the target tissue.

The air quality and health co-benefits of alternative post-2020 pathways for achieving peak carbon targets in Jiangsu, China

NASA Astrophysics Data System (ADS)

Liu, M.; Bi, J.; Huang, Y.; Kinney, P. L.

2016-12-01

Jiangsu, which has three national low-carbon pilot cities, is set to be a model province in China for achieving peak carbon targets before 2030. However, according to local planning of responding to climate change, carbon emissions are projected to keep going up before 2020 even the strictest measures are implemented. In other words, innovative measures must be in action after 2020. This work aimed at assessing the air quality and health co-benefits of alternative post-2020 measures to help remove barriers of policy implementation through tying it to local incentives for air quality improvement. To achieve the aim, we select 2010 as baseline year and develop Bussiness As Usual (BAU) and Traditional Carbon Reduction (TCR) scenarios before 2020. Under BAU, only existing climate and air pollution control policies are considered; under TCR, potential climate policies in local planning and existing air pollution control policies are considered. After 2020, integrated gasification combined cycle (IGCC) plant with carbon capture and storage (CCS) technology and large-scale substitution of renewable energy seem to be two promising pathways for achieving peak carbon targets. Therefore, two additional scenarios (TCR-IGCC and TCR-SRE) are set after 2020. Based on the projections of future energy balances and industrial productions, we estimate the pollutant emissions and simulate PM2.5 and ozone concentrations by 2017, 2020, 2030 and 2050 using CMAQ. Then using health impact assessment approach, the premature deaths are estimated and monetized. Results show that the carbon peak in Jiangsu will be achieved before 2030 only under TCR-IGCC and TCR-SRE scenarios. Under three policy scenarios, Jiangsu's carbon emission control targets would have substantial effects on primary air pollutant emissions far beyond those we estimate would be needed to meet the PM2.5 concentration targets in 2017. Compared with IGCC with CCS, large-scale substitutions of renewable energy bring comparable pollutant emission reductions but more health benefits because it reduces more emissions from traffic sources which are more harmful to health. However, large-scale substitution of renewable energy posed challenges on energy supply capacity, which need to be seriously considered in future policy decision.

A Community-Based Sensory Training Program Leads to Improved Experience at a Local Zoo for Children with Sensory Challenges.

PubMed

Kong, Michele; Pritchard, Mallory; Dean, Lara; Talley, Michele; Torbert, Roger; Maha, Julian

2017-01-01

Sensory processing difficulties are common among many special needs children, especially those with autism spectrum disorder (ASD). The sensory sensitivities often result in interference of daily functioning and can lead to social isolation for both the individual and family unit. A quality improvement (QI) project was undertaken within a local zoo to systematically implement a sensory training program targeted at helping special needs individuals with sensory challenges, including those with ASD, Down's syndrome, attention-deficit/hyperactivity disorder, and speech delay. We piloted the program over a 2-year period. The program consisted of staff training, provision of sensory bags and specific social stories, as well as creation of quiet zones. Two hundred family units were surveyed before and after implementation of the sensory training program. In this pilot QI study, families reported increased visitation to the zoo, improved interactions with staff members, and the overall quality of their experience. In conclusion, we are able to demonstrate that a sensory training program within the community zoo is feasible, impactful, and has the potential to decrease social isolation for special needs individuals and their families.

A Community-Based Sensory Training Program Leads to Improved Experience at a Local Zoo for Children with Sensory Challenges

PubMed Central

Kong, Michele; Pritchard, Mallory; Dean, Lara; Talley, Michele; Torbert, Roger; Maha, Julian

2017-01-01

Sensory processing difficulties are common among many special needs children, especially those with autism spectrum disorder (ASD). The sensory sensitivities often result in interference of daily functioning and can lead to social isolation for both the individual and family unit. A quality improvement (QI) project was undertaken within a local zoo to systematically implement a sensory training program targeted at helping special needs individuals with sensory challenges, including those with ASD, Down’s syndrome, attention-deficit/hyperactivity disorder, and speech delay. We piloted the program over a 2-year period. The program consisted of staff training, provision of sensory bags and specific social stories, as well as creation of quiet zones. Two hundred family units were surveyed before and after implementation of the sensory training program. In this pilot QI study, families reported increased visitation to the zoo, improved interactions with staff members, and the overall quality of their experience. In conclusion, we are able to demonstrate that a sensory training program within the community zoo is feasible, impactful, and has the potential to decrease social isolation for special needs individuals and their families. PMID:28966920

Improving local health workers' knowledge of malaria in the elimination phase-determinants and strategies: a cross-sectional study in rural China.

PubMed

Wang, Ruoxi; Tang, Shangfeng; Yang, Jun; Shao, Tian; Shao, Piaopiao; Liu, Chunyan; Feng, Da; Fu, Hang; Chen, Xiaoyu; Hu, Tao; Feng, Zhanchun

2017-05-19

The current stage of malaria elimination in China requires experienced local health workers with sufficient knowledge of malaria who help to keep the public health system vigilant about a possible resurgence. However, the influencing factors of local health workers' knowledge level are not fully comprehended. This study aims to explore the factors with heavy impact on local health worker's knowledge of malaria and propose corresponding suggestions. Underpinned by stratified sampling method, a cross-sectional survey was carried out between November 2014 and April 2016. Chi square test was performed to identify the factors with potential influence on health workers' knowledge level of malaria. Bivariate logistic regression was employed to explore the relationship between the predictors and local health workers' knowledge level of malaria. Layered Chi square test was used to calculate the homogeneity of the interaction between training approaches and the percentage of participants with high-level knowledge. The endemic type of county and type of organization played the most significant role in influencing local health workers' knowledge level regarding malaria in the sample population. The participants from Type 1 and Type 2 counties were 4.3 times (4.336 and 4.328, respectively) more likely to have high-level knowledge of malaria than those who work in Type 3 counties. The probability of having high-level knowledge amongst the participants from county-level facilities (county hospitals and CDCs) were more than 2.2 times higher than those who work in villages. Other socio-demographic factors, such as education and work experience, also affected one's knowledge regarding malaria. Amongst the six most-used training approaches, electronic material (OR = 2.356, 95% CI 1.112-4.989), thematic series (OR = 1.784, 95% CI 0.907-3.508) and supervision (OR = 2.788, 95% CI 1.018-7.632) were proven with significant positive impact on local health workers' knowledge of malaria. Village doctors and who served in Type 3 counties were identified as the ones in urgent need of effective training. Three types of training approaches, including electronic material, thematic series and supervision, were proven to be effective in improving local health workers' knowledge. Nevertheless, the coverage of these training approaches was still limited. This study suggests expanding the coverage of training, especially the three particular types of training, to local health workers, particularly to the target populations (village doctors and who served in Type 3 counties). Online training, small group discussion and targeted skill development may be the directions for the future development of training programmes.

The demonstration of a theory-based approach to the design of localized patient safety interventions

PubMed Central

2013-01-01

Background There is evidence of unsafe care in healthcare systems globally. Interventions to implement recommended practice often have modest and variable effects. Ideally, selecting and adapting interventions according to local contexts should enhance effects. However, the means by which this can happen is seldom systematic, based on theory, or made transparent. This work aimed to demonstrate the applicability, feasibility, and acceptability of a theoretical domains framework implementation (TDFI) approach for co-designing patient safety interventions. Methods We worked with three hospitals to support the implementation of evidence-based guidance to reduce the risk of feeding into misplaced nasogastric feeding tubes. Our stepped process, informed by the TDF and key principles from implementation literature, entailed: involving stakeholders; identifying target behaviors; identifying local factors (barriers and levers) affecting behavior change using a TDF-based questionnaire; working with stakeholders to generate specific local strategies to address key barriers; and supporting stakeholders to implement strategies. Exit interviews and audit data collection were undertaken to assess the feasibility and acceptability of this approach. Results Following audit and discussion, implementation teams for each Trust identified the process of checking the positioning of nasogastric tubes prior to feeding as the key behavior to target. Questionnaire results indicated differences in key barriers between organizations. Focus groups generated innovative, generalizable, and adaptable strategies for overcoming barriers, such as awareness events, screensavers, equipment modifications, and interactive learning resources. Exit interviews identified themes relating to the benefits, challenges, and sustainability of this approach. Time trend audit data were collected for 301 patients over an 18-month period for one Trust, suggesting clinically significant improved use of pH and documentation of practice following the intervention. Conclusions The TDF is a feasible and acceptable framework to guide the implementation of patient safety interventions. The stepped TDFI approach engages healthcare professionals and facilitates contextualization in identifying the target behavior, eliciting local barriers, and selecting strategies to address those barriers. This approach may be of use to implementation teams and policy makers, although our promising findings confirm the need for a more rigorous evaluation; a balanced block evaluation is currently underway. PMID:24131864

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bieniosek, F.M.; Anders, A.; Barnard, J.J.

This effort contains two main components: The new induction-bunching module is expected to deliver higher fluence in the bunched beam, and the new target positioner will enable a significantly enhanced target physics repetition rate. The velocity ramp that bunches the K{sup +} beam in the neutralized drift compression section is established with a bipolar voltage ramp applied to an acceleration gap. An induction acceleration module creates this voltage waveform. The new bunching module (IBM) specially built for NDCX has approximately twice the capability (volt-seconds) as our original IBM. We reported on the beam line design for the best use ofmore » the bunching module in our FY08 Q2 report. Based on simulations and theoretical work, we chose to extend the drift compression section and use the additional volt-seconds to extend the pulse duration and keep the peak voltage swing (and velocity excursions) similar to the present module. Simulations showed that this approach, which extends the drift section, to be advantageous because it limits the chromatic aberrations in the beam spot on target. To this end, colleagues at PPPL have fabricated the meter-long extension to the ferroelectric plasma source and it was installed on the beam line with the new IBM in January 2009. Simulation results suggest a factor of two increase in energy deposition from the bunched beam. In the first WDM target run (August-November 2008) the target handling setup required opening the vacuum system to manually replace the target after each shot (which destroys the target). Because of the requirement for careful alignment of each individual target, the target shot repetition rate was no greater than 1 shot per day. Initial results of this run are reported in our FY08 4th Quarter Milestone Report. Based on the valuable experience gained in the initial run, we have designed and installed an improved target alignment and positioning system with the capability to reposition targets remotely. This capability allows us to significantly increase our shot repetition rate, and to take greater advantage of the pinhole/cone arrangement we have developed to localize the beam at final focus. In addition we have improved the capability of the optical diagnostic systems, and we have installed a new beam current transformer downstream of the target to monitor beam current transmitted through the target during an experiment. These improvements will allow us to better exploit the inherent capability of the NDCX facility for high repetition rate and thus to provide more detailed experimental data to assess WDM physics models of target behavior. This milestone has been met by demonstrating highly compressed beams with the new bunching module, which are neutralized in the longer drift compression section by the new ferro-electric plasma sources. The peak uncompressed beam intensity ({approx}600 kW/cm{sup 2}) is higher than in previous measurements, and the bunched beam current profiles are {approx}2ns. We have also demonstrated a large increase in the experimental data acquisition rate for target heating experiments. In the first test of the new remote-controlled target positioning system, we completed three successful target physics shots in less than two hours. Further improvements are expected.« less

Daily Management System of the Henry Ford Production System: QTIPS to Focus Continuous Improvements at the Level of the Work.

PubMed

Zarbo, Richard J; Varney, Ruan C; Copeland, Jacqueline R; D'Angelo, Rita; Sharma, Gaurav

2015-07-01

To support our Lean culture of continuous improvement, we implemented a daily management system designed so critical metrics of operational success were the focus of local teams to drive improvements. We innovated a standardized visual daily management board composed of metric categories of Quality, Time, Inventory, Productivity, and Safety (QTIPS); frequency trending; root cause analysis; corrective/preventive actions; and resulting process improvements. In 1 year (June 2013 to July 2014), eight laboratory sections at Henry Ford Hospital employed 64 unique daily metrics. Most assessed long-term (>6 months), monitored process stability, while short-term metrics (1-6 months) were retired after successful targeted problem resolution. Daily monitoring resulted in 42 process improvements. Daily management is the key business accountability subsystem that enabled our culture of continuous improvement to function more efficiently at the managerial level in a visible manner by reviewing and acting based on data and root cause analysis. Copyright© by the American Society for Clinical Pathology.

Active Electro-Location of Objects in the Underwater Environment Based on the Mixed Polarization Multiple Signal Classification Algorithm

PubMed Central

Guo, Lili; Qi, Junwei; Xue, Wei

2018-01-01

This article proposes a novel active localization method based on the mixed polarization multiple signal classification (MP-MUSIC) algorithm for positioning a metal target or an insulator target in the underwater environment by using a uniform circular antenna (UCA). The boundary element method (BEM) is introduced to analyze the boundary of the target by use of a matrix equation. In this method, an electric dipole source as a part of the locating system is set perpendicularly to the plane of the UCA. As a result, the UCA can only receive the induction field of the target. The potential of each electrode of the UCA is used as spatial-temporal localization data, and it does not need to obtain the field component in each direction compared with the conventional fields-based localization method, which can be easily implemented in practical engineering applications. A simulation model and a physical experiment are constructed. The simulation and the experiment results provide accurate positioning performance, with the help of verifying the effectiveness of the proposed localization method in underwater target locating. PMID:29439495

Experimental investigation of a general real-time 3D target localization method using sequential kV imaging combined with respiratory monitoring.

PubMed

Cho, Byungchul; Poulsen, Per; Ruan, Dan; Sawant, Amit; Keall, Paul J

2012-11-21

The goal of this work was to experimentally quantify the geometric accuracy of a novel real-time 3D target localization method using sequential kV imaging combined with respiratory monitoring for clinically realistic arc and static field treatment delivery and target motion conditions. A general method for real-time target localization using kV imaging and respiratory monitoring was developed. Each dimension of internal target motion T(x, y, z; t) was estimated from the external respiratory signal R(t) through the correlation between R(t(i)) and the projected marker positions p(x(p), y(p); t(i)) on kV images by a state-augmented linear model: T(x, y, z; t) = aR(t) + bR(t - τ) + c. The model parameters, a, b, c, were determined by minimizing the squared fitting error ∑‖p(x(p), y(p); t(i)) - P(θ(i)) · (aR(t(i)) + bR(t(i) - τ) + c)‖(2) with the projection operator P(θ(i)). The model parameters were first initialized based on acquired kV arc images prior to MV beam delivery. This method was implemented on a trilogy linear accelerator consisting of an OBI x-ray imager (operating at 1 Hz) and real-time position monitoring (RPM) system (30 Hz). Arc and static field plans were delivered to a moving phantom programmed with measured lung tumour motion from ten patients. During delivery, the localization method determined the target position and the beam was adjusted in real time via dynamic multileaf collimator (DMLC) adaptation. The beam-target alignment error was quantified by segmenting the beam aperture and a phantom-embedded fiducial marker on MV images and analysing their relative position. With the localization method, the root-mean-squared errors of the ten lung tumour traces ranged from 0.7-1.3 mm and 0.8-1.4 mm during the single arc and five-field static beam delivery, respectively. Without the localization method, these errors ranged from 3.1-7.3 mm. In summary, a general method for real-time target localization using kV imaging and respiratory monitoring has been experimentally investigated for arc and static field delivery. The average beam-target error was 1 mm.

Experimental investigation of a general real-time 3D target localization method using sequential kV imaging combined with respiratory monitoring

NASA Astrophysics Data System (ADS)

Cho, Byungchul; Poulsen, Per; Ruan, Dan; Sawant, Amit; Keall, Paul J.

2012-11-01

The goal of this work was to experimentally quantify the geometric accuracy of a novel real-time 3D target localization method using sequential kV imaging combined with respiratory monitoring for clinically realistic arc and static field treatment delivery and target motion conditions. A general method for real-time target localization using kV imaging and respiratory monitoring was developed. Each dimension of internal target motion T(x, y, z; t) was estimated from the external respiratory signal R(t) through the correlation between R(ti) and the projected marker positions p(xp, yp; ti) on kV images by a state-augmented linear model: T(x, y, z; t) = aR(t) + bR(t - τ) + c. The model parameters, a, b, c, were determined by minimizing the squared fitting error ∑‖p(xp, yp; ti) - P(θi) · (aR(ti) + bR(ti - τ) + c)‖2 with the projection operator P(θi). The model parameters were first initialized based on acquired kV arc images prior to MV beam delivery. This method was implemented on a trilogy linear accelerator consisting of an OBI x-ray imager (operating at 1 Hz) and real-time position monitoring (RPM) system (30 Hz). Arc and static field plans were delivered to a moving phantom programmed with measured lung tumour motion from ten patients. During delivery, the localization method determined the target position and the beam was adjusted in real time via dynamic multileaf collimator (DMLC) adaptation. The beam-target alignment error was quantified by segmenting the beam aperture and a phantom-embedded fiducial marker on MV images and analysing their relative position. With the localization method, the root-mean-squared errors of the ten lung tumour traces ranged from 0.7-1.3 mm and 0.8-1.4 mm during the single arc and five-field static beam delivery, respectively. Without the localization method, these errors ranged from 3.1-7.3 mm. In summary, a general method for real-time target localization using kV imaging and respiratory monitoring has been experimentally investigated for arc and static field delivery. The average beam-target error was 1 mm.

Health promotion activities in annual reports of local governments: 'Health for All' targets as a tool for content analysis.

PubMed

Andersson, Camilla M; Bjärås, Gunilla E M; Tillgren, Per; Ostenson, Claes-Göran

2003-09-01

This article presents an instrument to study the annual reporting of health promotion activities in local governments within the three intervention municipalities of the Stockholm Diabetes Prevention Program (SDPP). The content of health promotion activities are described and the strengths, weaknesses and relevance of the method to health promotion discussed. A content analysis of local governmental reports from 1995-2000 in three Swedish municipalities. A matrix with WHO's 38 'Health for All' (HFA) targets from 1991 was used when coding the local health promotion activities. There are many public health initiatives within the local governmental structure even if they are not always addressed as health promotion. The main focuses in the local governmental reports were environmental issues, unemployment, social care and welfare. Local governmental reports were found to be a useful source of information that could provide knowledge about the priorities and organizational capacities for health promotion within local authorities. Additionally the HFA targets were an effective tool to identify and categorize systematically local health promotion activities in the annual reports of local governments. Identifying local health promotion initiatives by local authorities may ease the development of a health perspective and joint actions within the existing political and administrative structure. This paper provides a complementary method of attaining and structuring information about the local community for developments in health promotion.

Mitochondrial targeting increases specific activity of a heterologous valine assimilation pathway in Saccharomyces cerevisiae.

PubMed

Solomon, Kevin V; Ovadia, Elisa; Yu, Fujio; Mizunashi, Wataru; O'Malley, Michelle A

2016-12-01

Bio-based isobutantol is a sustainable 'drop in' substitute for petroleum-based fuels. However, well-studied production routes, such as the Ehrlich pathway, have yet to be commercialized despite more than a century of research. The more versatile bacterial valine catabolism may be a competitive alternate route producing not only an isobutanol precursor but several carboxylic acids with applications as biomonomers, and building blocks for other advanced biofuels. Here, we transfer the first two committed steps of the pathway from pathogenic Pseudomonas aeruginosa PAO1 to yeast to evaluate their activity in a safer model organism. Genes encoding the heteroligomeric branched chain keto-acid dehydrogenase (BCKAD; bkdA1, bkdA2, bkdB, lpdV ), and the homooligomeric acyl-CoA dehydrogenase (ACD; acd1 ) were tagged with fluorescence epitopes and targeted for expression in either the mitochondria or cytoplasm of S. cerevisiae . We verified the localization of our constructs with confocal fluorescence microscopy before measuring the activity of tag-free constructs. Despite reduced heterologous expression of mitochondria-targeted enzymes, their specific activities were significantly improved with total enzyme activities up to 138% greater than those of enzymes expressed in the cytoplasm. In total, our results demonstrate that the choice of protein localization in yeast has significant impact on heterologous activity, and suggests a new path forward for isobutanol production.

Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy

PubMed Central

Ashton, Jeffrey R.; Castle, Katherine D.; Qi, Yi; Kirsch, David G.; West, Jennifer L.; Badea, Cristian T.

2018-01-01

Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and computed tomography (CT) imaging. AuNPs absorb x-rays and subsequently release low-energy, short-range photoelectrons during external beam radiation therapy (RT), increasing the local radiation dose. When AuNPs are near tumor vasculature, the additional radiation dose can lead to increased vascular permeability. This work focuses on understanding how tumor vascular permeability is influenced by AuNP-augmented RT, and how this effect can be used to improve the delivery of nanoparticle chemotherapeutics. Methods: Dual-energy CT was used to quantify the accumulation of both liposomal iodine and AuNPs in tumors following AuNP-augmented RT in a mouse model of primary soft tissue sarcoma. Mice were injected with non-targeted AuNPs, RGD-functionalized AuNPs (vascular targeting), or no AuNPs, after which they were treated with varying doses of RT. The mice were injected with either liposomal iodine (for the imaging study) or liposomal doxorubicin (for the treatment study) 24 hours after RT. Increased tumor liposome accumulation was assessed by dual-energy CT (iodine) or by tracking tumor treatment response (doxorubicin). Results: A significant increase in vascular permeability was observed for all groups after 20 Gy RT, for the targeted and non-targeted AuNP groups after 10 Gy RT, and for the vascular-targeted AuNP group after 5 Gy RT. Combining targeted AuNPs with 5 Gy RT and liposomal doxorubicin led to a significant tumor growth delay (tumor doubling time ~ 8 days) compared to AuNP-augmented RT or chemotherapy alone (tumor doubling time ~3-4 days). Conclusions: The addition of vascular-targeted AuNPs significantly improved the treatment effect of liposomal doxorubicin after RT, consistent with the increased liposome accumulation observed in tumors in the imaging study. Using this approach with a liposomal drug delivery system can increase specific tumor delivery of chemotherapeutics, which has the potential to significantly improve tumor response and reduce the side effects of both RT and chemotherapy. PMID:29556356

Gene therapy for ocular diseases meditated by ultrasound and microbubbles (Review)

PubMed Central

WAN, CAIFENG; LI, FENGHUA; LI, HONGLI

2015-01-01

The eye is an ideal target organ for gene therapy as it is easily accessible and immune-privileged. With the increasing insight into the underlying molecular mechanisms of ocular diseases, gene therapy has been proposed as an effective approach. Successful gene therapy depends on efficient gene transfer to targeted cells to prove stable and prolonged gene expression with minimal toxicity. At present, the main hindrance regarding the clinical application of gene therapy is not the lack of an ideal gene, but rather the lack of a safe and efficient method to selectively deliver genes to target cells and tissues. Ultrasound-targeted microbubble destruction (UTMD), with the advantages of high safety, repetitive applicability and tissue targeting, has become a potential strategy for gene- and drug delivery. When gene-loaded microbubbles are injected, UTMD is able to enhance the transport of the gene to the targeted cells. High-amplitude oscillations of microbubbles act as cavitation nuclei which can effectively focus ultrasound energy, produce oscillations and disruptions that increase the permeability of the cell membrane and create transient pores in the cell membrane. Thereby, the efficiency of gene therapy can be significantly improved. The UTMD-mediated gene delivery system has been widely used in pre-clinical studies to enhance gene expression in a site-specific manner in a variety of organs. With reasonable application, the effects of sonoporation can be spatially and temporally controlled to improve localized tissue deposition of gene complexes for ocular gene therapy applications. In addition, appropriately powered, focused ultrasound combined with microbubbles can induce a reversible disruption of the blood-retinal barrier with no significant side effects. The present review discusses the current status of gene therapy of ocular diseases as well as studies on gene therapy of ocular diseases meditated by UTMD. PMID:26151686

Modeling Airborne Gravity Data with Local Functions for Regional Geoid Enhancement ---- A Case Study in Puerto Rico Area

NASA Astrophysics Data System (ADS)

Li, Xiaopeng

2016-04-01

Airborne gravimetry has been used as the primary method to quickly and economically obtain updated gravity field information over a region, targeted specifically. Thus, unlike the satellite missions that provide global or near global data coverage, the observables from airborne campaigns are apparently space limited. Moreover, they are also band limited in the frequency domain, considering that various filter banks and/or de-noising techniques have to be applied to overcome the low signal to noise ratio problem that are presented in the airborne systems due to mechanical and mathematical limitations in computing the accelerations, both the kinematic one and the dynamic one. As a result, in this study, a band-limited local function system based on the point mass model is used to process these airborne gravity data that have both a limited frequency domain and a limited space domain in the target area: Puerto Rico Island and its nearby ocean areas. The resulting geoid model show obvious middle to short wavelength geoid changes due to airborne gravity data contribution. In the land area, these changes improved the geoid precision from 3.27cm to 2.09cm at the local GNSS/Leveling bench marks. More importantly, the error trend in the geoid models is largely reduced if not completely removed. Various oceanographic models will be used to validate the geoid changes in the nearby open sea areas.

Construction of an Overhauser magnetic gradiometer and the applications in geomagnetic observation and ferromagnetic target localization

NASA Astrophysics Data System (ADS)

Liu, H.; Dong, H.; Liu, Z.; Ge, J.; Bai, B.; Zhang, C.

2017-10-01

The proton precession magnetometer with single sensor is commonly used in geomagnetic observation and magnetic anomaly detection. Due to technological limitations, the measurement accuracy is restricted by several factors such as the sensor performance, frequency measurement precision, instability of polarization module, etc. Aimed to improve the anti-interference ability, an Overhauser magnetic gradiometer with dual sensor structure was designed. An alternative design of a geomagnetic sensor with differential dual-coil structure was presented. A multi-channel frequency measurement algorithm was proposed to increase the measurement accuracy. A silicon oscillator was adopted to resolve the instability of polarization system. This paper briefly discusses the design and development of the gradiometer and compares the data recorded by this instrument with a commonly used commercially Overhauser magnetometer in the world market. The proposed gradiometer records the earth magnetic field in 24 hours with measurement accuracy of ± 0.3 nT and a sampling rate of 3 seconds per sample. The quality of data recorded is excellent and consistent with the commercial instrument. In addition, experiments of ferromagnetic target localization were conducted. This gradiometer shows a strong ability in magnetic anomaly detection and localization. To sum up, it has the advantages of convenient operation, high precision, strong anti-interference, etc., which proves the effectiveness of the dual sensor structure Overhauser magnetic gradiometer.

Target detection and localization in shallow water: an experimental demonstration of the acoustic barrier problem at the laboratory scale.

PubMed

Marandet, Christian; Roux, Philippe; Nicolas, Barbara; Mars, Jérôme

2011-01-01

This study demonstrates experimentally at the laboratory scale the detection and localization of a wavelength-sized target in a shallow ultrasonic waveguide between two source-receiver arrays at 3 MHz. In the framework of the acoustic barrier problem, at the 1/1000 scale, the waveguide represents a 1.1-km-long, 52-m-deep ocean acoustic channel in the kilohertz frequency range. The two coplanar arrays record in the time-domain the transfer matrix of the waveguide between each pair of source-receiver transducers. Invoking the reciprocity principle, a time-domain double-beamforming algorithm is simultaneously performed on the source and receiver arrays. This array processing projects the multireverberated acoustic echoes into an equivalent set of eigenrays, which are defined by their launch and arrival angles. Comparison is made between the intensity of each eigenray without and with a target for detection in the waveguide. Localization is performed through tomography inversion of the acoustic impedance of the target, using all of the eigenrays extracted from double beamforming. The use of the diffraction-based sensitivity kernel for each eigenray provides both the localization and the signature of the target. Experimental results are shown in the presence of surface waves, and methodological issues are discussed for detection and localization.

Immobilization of FLAG-Tagged Recombinant Adeno-Associated Virus 2 onto Tissue Engineering Scaffolds for the Improvement of Transgene Delivery in Cell Transplants.

PubMed

Li, Hua; Zhang, Feng-Lan; Shi, Wen-Jie; Bai, Xue-Jia; Jia, Shu-Qin; Zhang, Chen-Guang; Ding, Wei

2015-01-01

The technology of virus-based genetic modification in tissue engineering has provided the opportunity to produce more flexible and versatile biomaterials for transplantation. Localizing the transgene expression with increased efficiency is critical for tissue engineering as well as a challenge for virus-based gene delivery. In this study, we tagged the VP2 protein of type 2 adeno-associated virus (AAV) with a 3×FLAG plasmid at the N-terminus and packaged a FLAG-tagged recombinant AAV2 chimeric mutant. The mutant AAVs were immobilized onto the tissue engineering scaffolds with crosslinked anti-FLAG antibodies by N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP). Cultured cells were seeded to scaffolds to form 3D transplants, and then tested for viral transduction both in vitro and in vivo. The results showed that our FLAG-tagged AAV2 exerted similar transduction efficiency compared with the wild type AAV2 when infected cultured cells. Following immobilization onto the scaffolds of PLGA or gelatin sponge with anti-FLAG antibodies, the viral mediated transgene expression was significantly improved and more localized. Our data demonstrated that the mutation of AAV capsid targeted for antibody-based immobilization could be a practical approach for more efficient and precise transgene delivery. It was also suggested that the immobilization of AAV might have attractive potentials in applications of tissue engineering involving the targeted gene manipulation in 3D tissue cultures.

Metabolic Engineering of Probiotic Saccharomyces boulardii.

PubMed

Liu, Jing-Jing; Kong, In Iok; Zhang, Guo-Chang; Jayakody, Lahiru N; Kim, Heejin; Xia, Peng-Fei; Kwak, Suryang; Sung, Bong Hyun; Sohn, Jung-Hoon; Walukiewicz, Hanna E; Rao, Christopher V; Jin, Yong-Su

2016-04-01

Saccharomyces boulardiiis a probiotic yeast that has been used for promoting gut health as well as preventing diarrheal diseases. This yeast not only exhibits beneficial phenotypes for gut health but also can stay longer in the gut than Saccharomyces cerevisiae Therefore, S. boulardiiis an attractive host for metabolic engineering to produce biomolecules of interest in the gut. However, the lack of auxotrophic strains with defined genetic backgrounds has hampered the use of this strain for metabolic engineering. Here, we report the development of well-defined auxotrophic mutants (leu2,ura3,his3, and trp1) through clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-based genome editing. The resulting auxotrophic mutants can be used as a host for introducing various genetic perturbations, such as overexpression or deletion of a target gene, using existing genetic tools forS. cerevisiae We demonstrated the overexpression of a heterologous gene (lacZ), the correct localization of a target protein (red fluorescent protein) into mitochondria by using a protein localization signal, and the introduction of a heterologous metabolic pathway (xylose-assimilating pathway) in the genome ofS. boulardii We further demonstrated that human lysozyme, which is beneficial for human gut health, could be secreted by S. boulardii Our results suggest that more sophisticated genetic perturbations to improveS. boulardii can be performed without using a drug resistance marker, which is a prerequisite for in vivo applications using engineeredS. boulardii. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Identification and Characterization of microRNA319a and Its Putative Target Gene, PvPCF5, in the Bioenergy Grass Switchgrass (Panicum virgatum).

PubMed

Xie, Qi; Liu, Xue; Zhang, Yinbing; Tang, Jinfu; Yin, Dedong; Fan, Bo; Zhu, Lihuang; Han, Liebao; Song, Guilong; Li, Dayong

2017-01-01

Due to its high biomass yield, low environmental impact, and widespread adaptability to poor soils and harsh conditions, switchgrass ( Panicum virgatum L.), a warm-region perennial herbaceous plant, has attracted much attention in recent years. However, little is known about microRNAs (miRNAs) and their functions in this bioenergy grass. Here, we identified and characterized a miRNA gene, Pvi-MIR319a , encoding microRNA319a in switchgrass. Transgenic rice lines generated by overexpressing the Pvi-MIR319a precursor gene exhibited broader leaves and delayed flowering compared with the control. Gene expression analysis indicated at least four putative target genes were downregulated. Additionally, we cloned a putative target gene ( PvPCF5 ) of Pvi-MIR319a from switchgrass. PvPCF5, a TCP transcription factor, is a nuclear-localized protein with transactivation activity and control the development of leaf. Our results suggest that Pvi-MIR319a and its target genes may be used as potential genetic regulators for future switchgrass genetic improvement.

Enhancement and Passive Acoustic Mapping of Cavitation from Fluorescently Tagged Magnetic Resonance-Visible Magnetic Microbubbles In Vivo.

PubMed

Crake, Calum; Owen, Joshua; Smart, Sean; Coviello, Christian; Coussios, Constantin-C; Carlisle, Robert; Stride, Eleanor

2016-12-01

Previous work has indicated the potential of magnetically functionalized microbubbles to localize and enhance cavitation activity under focused ultrasound exposure in vitro. The aim of this study was to investigate magnetic targeting of microbubbles for promotion of cavitation in vivo. Fluorescently labelled magnetic microbubbles were administered intravenously in a murine xenograft model. Cavitation was induced using a 0.5-MHz focused ultrasound transducer at peak negative focal pressures of 1.2-2.0 MPa and monitored in real-time using B-mode imaging and passive acoustic mapping. Magnetic targeting was found to increase the amplitude of the cavitation signal by approximately 50% compared with untargeted bubbles. Post-exposure magnetic resonance imaging indicated deposition of magnetic nanoparticles in tumours. Magnetic targeting was similarly associated with increased fluorescence intensity in the tumours after the experiments. These results suggest that magnetic targeting could potentially be used to improve delivery of cavitation-mediated therapy and that passive acoustic mapping could be used for real-time monitoring of this process. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of TEL Confusers on Operator Target Acquisition Performance with SAR Imagery

DTIC Science & Technology

1998-12-01

processing known as the theory of signal detection (TSD) (Gescheider, 1985; Green & Swets, 1966; Macmillan & Creelman , 1991; Wilson, 1992). A TSD...localizations (Hacker & Ratcliff, 1979; Macmillan & Creelman , 1991). The index of bias in a target localization task provides a measure of the operator’s...of correct localizations substituted for hits (Macmillan & Creelman , 1991). Receiver Operating Characteristic Curves. In addition to the calculation

[Systemic treatment of brain metastases from breast cancer: cytotoxic chemotherapy and targeted therapies].

PubMed

Bachelot, Thomas; Le Rhun, Emilie; Labidi-Gally, Intidar; Heudel, Pierre; Gilabert, Marine; Bonneterre, Jacques; Pierga, Jean-Yves; Gonçalves, Anthony

2013-01-01

Prevalence of brain metastases is increasing in breast cancer. Brain metastases represent a poor-prognosis disease for which local treatments continue to play a major role. In spite of the presence of a physiological blood-brain barrier limiting their activity, some systemic treatments may display a significant antitumor activity at the central nervous system level. In HER2-positive metastatic breast cancer with brain metastases not previously treated with whole brain radiotherapy, capecitabine and lapatinib combination obtains a volumetric reponse in two thirds of patients (LANDSCAPE study). If confirmed, these results could modify in selected patients the layout of therapeutic strategies. Promoting novel targeted approaches and innovative therapeutic combinations is a critical need to improve survival of breast cancer patients with brain metastases.

Biomimetic proteolipid vesicles for targeting inflamed tissues

NASA Astrophysics Data System (ADS)

Molinaro, R.; Corbo, C.; Martinez, J. O.; Taraballi, F.; Evangelopoulos, M.; Minardi, S.; Yazdi, I. K.; Zhao, P.; De Rosa, E.; Sherman, M. B.; de Vita, A.; Toledano Furman, N. E.; Wang, X.; Parodi, A.; Tasciotti, E.

2016-09-01

A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles--which we refer to as leukosomes--retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.

Leading clinical handover improvement: a change strategy to implement best practices in the acute care setting.

PubMed

Clarke, Christina M; Persaud, Drepaul David

2011-03-01

Many contemporary acute care facilities lack safe and effective clinical handover practices resulting in patient transitions that are vulnerable to discontinuities in care, medical errors, and adverse patient safety events. This article is intended to supplement existing handover improvement literature by providing practical guidance for leaders and managers who are seeking to improve the safety and the effectiveness of clinical handovers in the acute care setting. A 4-stage change model has been applied to guide the application of strategies for handover improvement. Change management and quality improvement principles, as well as concepts drawn from safety science and high-reliability organizations, were applied to inform strategies. A model for handover improvement respecting handover complexity is presented. Strategies targeted to stages of change include the following: 1. Enhancing awareness of handover problems and opportunities with the support of strategic directions, accountability, end user involvement, and problem complexity recognition. 2. Identifying solutions by applying and adapting best practices in local contexts. 3. Implementing locally adapted best practices supported by communication, documentation, and training. 4. Institutionalizing practice changes through integration, monitoring, and active dissemination. Finally, continued evaluation at every stage is essential. Although gaps in handover process and function knowledge remain, efforts to improve handover safety and effectiveness are still possible. Continued evaluation is critical in building this understanding and to ensure that practice changes lead to improvements in patient safety, organizational effectiveness, and patient and provider satisfaction. Through handover knowledge building, fundamental changes in handover policies and practices may be possible.

Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

PubMed Central

Cox, Adrienne D.; Der, Channing J.; Philips, Mark R.

2015-01-01

RAS proteins require membrane association for their biological activity, making this association a logical target for anti-RAS therapeutics. Lipid modification of RAS proteins by a farnesyl isoprenoid is an obligate step in that association, and is an enzymatic process. Accordingly, farnesyltransferase inhibitors (FTIs) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anti-cancer drugs was widely seen as indicating that blocking RAS membrane association was a flawed approach to cancer treatment. However, a deeper understanding of RAS modification and trafficking has revealed that this was an erroneous conclusion. In the presence of FTIs, KRAS and NRAS, which are the RAS isoforms most frequently mutated in cancer, become substrates for alternative modification, can still associate with membranes, and can still function. Thus, FTIs failed not because blocking RAS membrane association is an ineffective approach, but because FTIs failed to accomplish that task. Recent findings regarding RAS isoform trafficking and the regulation of RAS subcellular localization have rekindled interest in efforts to target these processes. In particular, improved understanding of the palmitoylation/depalmitoylation cycle that regulates RAS interaction with the plasma membrane, endomembranes and cytosol, and of the potential importance of RAS chaperones, have led to new approaches. Efforts to validate and target other enzymatically regulated post-translational modifications are also ongoing. In this review, we revisit lessons learned, describe the current state of the art, and highlight challenging but promising directions to achieve the goal of disrupting RAS membrane association and subcellular localization for anti-RAS drug development. PMID:25878363

Do resource utilization and clinical measures still vary across dialysis chains after controlling for the local practices of facilities and physicians?

PubMed

Hirth, Richard A; Turenne, Marc N; Wheeler, John R C; Ma, Yu; Messana, Joseph M

2010-08-01

Because of adverse survival effects, anemia management and financial incentives to increase doses of erythropoiesis-stimulating agents (ESAs) have been controversial. Prior studies showed more aggressive anemia management in dialysis facilities owned by for-profit chains, but have been criticized for not accounting for practices of individual physicians and facilities. To improve understanding of how dialysis practices and resource utilization are influenced by physicians, facilities, and chains. Mixed models with chain fixed effects and facility and physician random effects. Medicare hemodialysis patients in 2004. A total of 234,158 patients, 3995 facilities, 4838 physicians, and 7 chain classifications were included. Spending per session for dialysis-related services billed separately from the dialysis treatment and for ESAs. Achievement of hematocrit (HCT) and urea reduction ratio (URR) targets. Of the 4 largest for-profit chains, 3 had higher resource use than independents, with differences up to $17.92 higher ESA/session. Utilization was positively associated with achieving target HCT. Despite incurring lower costs, patients treated by a large nonprofit chain were as likely as patients of independents to achieve the HCT target. The largest chains were more likely than independents to achieve the URR target. Substantial variation occurred across physicians and facilities, and adjustment for chain only modestly decreased this variation. Chains' methods of influencing practices were not directly observed. Chains appear to have the ability to implement protocols that shift practices, but not the ability to substantially reduce local variation. Assertions that chain effects found by earlier studies were spurious are not supported.

Evaluation of a head-repositioner and Z-plate system for improved accuracy of dose delivery.

PubMed

Charney, Sarah C; Lutz, Wendell R; Klein, Mary K; Jones, Pamela D

2009-01-01

Radiation therapy requires accurate dose delivery to targets often identifiable only on computed tomography (CT) images. Translation between the isocenter localized on CT and laser setup for radiation treatment, and interfractional head repositioning are frequent sources of positioning error. The objective was to design a simple, accurate apparatus to eliminate these sources of error. System accuracy was confirmed with phantom and in vivo measurements. A head repositioner that fixates the maxilla via dental mold with fiducial marker Z-plates attached was fabricated to facilitate the connection between the isocenter on CT and laser treatment setup. A phantom study targeting steel balls randomly located within the head repositioner was performed. The center of each ball was marked on a transverse CT slice on which six points of the Z-plate were also visible. Based on the relative position of the six Z-plate points and the ball center, the laser setup position on each Z-plate and a top plate was calculated. Based on these setup marks, orthogonal port films, directed toward each target, were evaluated for accuracy without regard to visual setup. A similar procedure was followed to confirm accuracy of in vivo treatment setups in four dogs using implanted gold seeds. Sequential port films of three dogs were made to confirm interfractional accuracy. Phantom and in vivo measurements confirmed accuracy of 2 mm between isocenter on CT and the center of the treatment dose distribution. Port films confirmed similar accuracy for interfractional treatments. The system reliably connects CT target localization to accurate initial and interfractional radiation treatment setup.

Robotic path-finding in inverse treatment planning for stereotactic radiosurgery with continuous dose delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vandewouw, Marlee M., E-mail: marleev@mie.utoronto

Purpose: Continuous dose delivery in radiation therapy treatments has been shown to decrease total treatment time while improving the dose conformity and distribution homogeneity over the conventional step-and-shoot approach. The authors develop an inverse treatment planning method for Gamma Knife® Perfexion™ that continuously delivers dose along a path in the target. Methods: The authors’ method is comprised of two steps: find a path within the target, then solve a mixed integer optimization model to find the optimal collimator configurations and durations along the selected path. Robotic path-finding techniques, specifically, simultaneous localization and mapping (SLAM) using an extended Kalman filter, aremore » used to obtain a path that travels sufficiently close to selected isocentre locations. SLAM is novelly extended to explore a 3D, discrete environment, which is the target discretized into voxels. Further novel extensions are incorporated into the steering mechanism to account for target geometry. Results: The SLAM method was tested on seven clinical cases and compared to clinical, Hamiltonian path continuous delivery, and inverse step-and-shoot treatment plans. The SLAM approach improved dose metrics compared to the clinical plans and Hamiltonian path continuous delivery plans. Beam-on times improved over clinical plans, and had mixed performance compared to Hamiltonian path continuous plans. The SLAM method is also shown to be robust to path selection inaccuracies, isocentre selection, and dose distribution. Conclusions: The SLAM method for continuous delivery provides decreased total treatment time and increased treatment quality compared to both clinical and inverse step-and-shoot plans, and outperforms existing path methods in treatment quality. It also accounts for uncertainty in treatment planning by accommodating inaccuracies.« less

New Agents, Emerging Late Effects, and the Development of Precision Survivorship.

PubMed

Chow, Eric J; Antal, Zoltan; Constine, Louis S; Gardner, Rebecca; Wallace, W Hamish; Weil, Brent R; Yeh, Jennifer M; Fox, Elizabeth

2018-06-06

Incremental improvements in the treatment of children and adolescents with cancer have led to 5-year survival rates reaching nearly 85%. In the past decade, impressive progress has been made in understanding the biology of many pediatric cancers. With that understanding, multiple new agents have become available that offer the promise of more-effective and less-toxic treatment. These include agents that target various cell surface antigens and engage the adaptive immune system, as well as those that interfere with key signaling pathways involved in tumor development and growth. For local control, surgery and radiation techniques also have evolved, becoming less invasive or featuring new techniques and particles that more precisely target the tumor and limit the dose to normal tissue. Nevertheless, targeted agents, like conventional chemotherapy, radiotherapy, and surgery, may have off-target effects and deserve long-term follow-up of their safety and efficacy. These include injury to the endocrine, cardiovascular, and immunologic systems. New radiation and surgical techniques that theoretically reduce morbidity and improve long-term quality of life must also be validated with actual patient outcomes. Finally, with advances in genomics, information on host susceptibility to late effects is beginning to emerge. Such knowledge, coupled with improved metrics that better describe the spectrum of potential late effects across the entire lifespan, can lead to the development of decision models that project the potential long-term health outcomes associated with various treatment and follow-up strategies. These developments will help extend the current focus on precision medicine to precision survivorship, where clinicians, patients, and families will have a better grasp of the potential risks, benefits, and tradeoffs associated with the growing number of cancer treatment options.

A range-based predictive localization algorithm for WSID networks

NASA Astrophysics Data System (ADS)

Liu, Yuan; Chen, Junjie; Li, Gang

2017-11-01

Most studies on localization algorithms are conducted on the sensor networks with densely distributed nodes. However, the non-localizable problems are prone to occur in the network with sparsely distributed sensor nodes. To solve this problem, a range-based predictive localization algorithm (RPLA) is proposed in this paper for the wireless sensor networks syncretizing the RFID (WSID) networks. The Gaussian mixture model is established to predict the trajectory of a mobile target. Then, the received signal strength indication is used to reduce the residence area of the target location based on the approximate point-in-triangulation test algorithm. In addition, collaborative localization schemes are introduced to locate the target in the non-localizable situations. Simulation results verify that the RPLA achieves accurate localization for the network with sparsely distributed sensor nodes. The localization accuracy of the RPLA is 48.7% higher than that of the APIT algorithm, 16.8% higher than that of the single Gaussian model-based algorithm and 10.5% higher than that of the Kalman filtering-based algorithm.

Assessing the clinical outcome of Vim radiosurgery with voxel-based morphometry: visual areas are linked with tremor arrest!

PubMed

Tuleasca, Constantin; Witjas, Tatiana; Najdenovska, Elena; Verger, Antoine; Girard, Nadine; Champoudry, Jerome; Thiran, Jean-Philippe; Van de Ville, Dimitri; Cuadra, Meritxell Bach; Levivier, Marc; Guedj, Eric; Régis, Jean

2017-11-01

Radiosurgery (RS) is an alternative to open standard stereotactic procedures (deep-brain stimulation or radiofrequency thalamotomy) for drug-resistant essential tremor (ET), aiming at the same target (ventro-intermediate nucleus, Vim). We investigated the Vim RS outcome using voxel-based morphometry by evaluating the interaction between clinical response and time. Thirty-eight patients with right-sided ET benefited from left unilateral Vim RS. Targeting was performed using 130 Gy and a single 4-mm collimator. Neurological and neuroimaging assessment was completed at baseline and 1 year. Clinical responders were considered those with at least 50% improvement in tremor score on the treated hand (TSTH). Interaction between clinical response and time showed the left temporal pole and occipital cortex (Brodmann area 19, including V4, V5 and the parahippocampal place area) as statistically significant. A decrease in gray matter density (GMD) 1 year after Vim RS correlated with higher TSTH improvement (Spearman = 0.01) for both anatomical areas. Higher baseline GMD within the left temporal pole correlated with better TSTH improvement (Spearman = 0.004). Statistically significant structural changes in the relationship to clinical response after Vim RS are present in remote areas, advocating a distant neurobiological effect. The former regions are mainly involved in locomotor monitoring toward the local and distant environment, suggesting the recruiting requirement in targeting of the specific visuomotor networks.

Protein (multi-)location prediction: using location inter-dependencies in a probabilistic framework

PubMed Central

2014-01-01

Motivation Knowing the location of a protein within the cell is important for understanding its function, role in biological processes, and potential use as a drug target. Much progress has been made in developing computational methods that predict single locations for proteins. Most such methods are based on the over-simplifying assumption that proteins localize to a single location. However, it has been shown that proteins localize to multiple locations. While a few recent systems attempt to predict multiple locations of proteins, their performance leaves much room for improvement. Moreover, they typically treat locations as independent and do not attempt to utilize possible inter-dependencies among locations. Our hypothesis is that directly incorporating inter-dependencies among locations into both the classifier-learning and the prediction process can improve location prediction performance. Results We present a new method and a preliminary system we have developed that directly incorporates inter-dependencies among locations into the location-prediction process of multiply-localized proteins. Our method is based on a collection of Bayesian network classifiers, where each classifier is used to predict a single location. Learning the structure of each Bayesian network classifier takes into account inter-dependencies among locations, and the prediction process uses estimates involving multiple locations. We evaluate our system on a dataset of single- and multi-localized proteins (the most comprehensive protein multi-localization dataset currently available, derived from the DBMLoc dataset). Our results, obtained by incorporating inter-dependencies, are significantly higher than those obtained by classifiers that do not use inter-dependencies. The performance of our system on multi-localized proteins is comparable to a top performing system (YLoc+), without being restricted only to location-combinations present in the training set. PMID:24646119

Protein (multi-)location prediction: using location inter-dependencies in a probabilistic framework.

PubMed

Simha, Ramanuja; Shatkay, Hagit

2014-03-19

Knowing the location of a protein within the cell is important for understanding its function, role in biological processes, and potential use as a drug target. Much progress has been made in developing computational methods that predict single locations for proteins. Most such methods are based on the over-simplifying assumption that proteins localize to a single location. However, it has been shown that proteins localize to multiple locations. While a few recent systems attempt to predict multiple locations of proteins, their performance leaves much room for improvement. Moreover, they typically treat locations as independent and do not attempt to utilize possible inter-dependencies among locations. Our hypothesis is that directly incorporating inter-dependencies among locations into both the classifier-learning and the prediction process can improve location prediction performance. We present a new method and a preliminary system we have developed that directly incorporates inter-dependencies among locations into the location-prediction process of multiply-localized proteins. Our method is based on a collection of Bayesian network classifiers, where each classifier is used to predict a single location. Learning the structure of each Bayesian network classifier takes into account inter-dependencies among locations, and the prediction process uses estimates involving multiple locations. We evaluate our system on a dataset of single- and multi-localized proteins (the most comprehensive protein multi-localization dataset currently available, derived from the DBMLoc dataset). Our results, obtained by incorporating inter-dependencies, are significantly higher than those obtained by classifiers that do not use inter-dependencies. The performance of our system on multi-localized proteins is comparable to a top performing system (YLoc+), without being restricted only to location-combinations present in the training set.

Nipah virus matrix protein: expert hacker of cellular machines.

PubMed

Watkinson, Ruth E; Lee, Benhur

2016-08-01

Nipah virus (NiV, Henipavirus) is a highly lethal emergent zoonotic paramyxovirus responsible for repeated human outbreaks of encephalitis in South East Asia. There are no approved vaccines or treatments, thus improved understanding of NiV biology is imperative. NiV matrix protein recruits a plethora of cellular machinery to scaffold and coordinate virion budding. Intriguingly, matrix also hijacks cellular trafficking and ubiquitination pathways to facilitate transient nuclear localization. While the biological significance of matrix nuclear localization for an otherwise cytoplasmic virus remains enigmatic, the molecular details have begun to be characterized, and are conserved among matrix proteins from divergent paramyxoviruses. Matrix protein appropriation of cellular machinery will be discussed in terms of its early nuclear targeting and later role in virion assembly. © 2016 Federation of European Biochemical Societies.

Photodynamic characterization and optimization using multifunctional nanoparticles for brain cancer treatment

NASA Astrophysics Data System (ADS)

Herrmann, Kristen; Lee Koo, Yong-Eun; Orringer, Daniel A.; Sagher, Oren; Philbert, Martin; Kopelman, Raoul

2013-03-01

Photosensitizer-conjugated polyacrylamide nanoparticles were prepared for in vivo characterization of the minimally invasive and localized treatment of photodynamic therapy (PDT) on brain tumors. By incorporating a variety of nanoparticle matrixes, choosing methylene blue as a photosensitizer, and targeting the nanoparticle by the use of F3 peptide we have made nanoparticle-based PDT improvements to current PDT efficiency. Quantitative growth patterns were determined through visual observation of the tumorigenic response to various treatments by the use of an animal cranial window model. PDT treatments with methylene blue-polyacrylamide (MB-PAA) nanoparticles produced significant adjournment of tumor growth over control groups, clearly demonstrating the advantages of nanoparticle-based PDT agents for the eradication of local tumors, leading to the potential palliation of the advancing disease.

The comparative effectiveness of mail order pharmacy use vs. local pharmacy use on LDL-C control in new statin users.

PubMed

Schmittdiel, Julie A; Karter, Andrew J; Dyer, Wendy; Parker, Melissa; Uratsu, Connie; Chan, James; Duru, O Kenrik

2011-12-01

Mail order pharmacies are commonly used to deliver CVD risk factor medications. Previous studies have shown that mail order pharmacy use is associated with greater medication adherence; however, no studies have examined whether mail order pharmacy use is related to improved CVD risk factor outcomes. To examine the comparative effectiveness of mail order pharmacy vs. local pharmacy use on LDL-C control in new statin users. Observational cohort study. 100,298 adult Kaiser Permanente Northern California (KPNC) members who were new users of statins between January 1, 2005 and December 31, 2007. The main outcome measure was LDL-C control in the 3-15 month period after statin therapy was initiated. After adjustment for patient, clinical, and census-block characteristics, and for potential unmeasured differences between mail order and local KPNC pharmacy users with instrumental variables analysis, 85.0% of patients who used the mail order pharmacy to deliver their statin at any time achieved target LDL-C levels compared with 74.2% of patients who only used the local KPNC pharmacy to dispense the statin (p < 0.001). Greater adjusted rates of LDL-C control in mail order pharmacy users were seen across all gender and race/ethnicity subgroups. Mail order pharmacy use was positively associated with LDL-C control in new statin users. Future research should continue to explore the relationship between mail order pharmacy use and outcomes, and address how to appropriately target mail order services to patients most likely to benefit without compromising patient choice, care, and safety.

Localized delivery of chemotherapy to the cervix for radiosensitization.

PubMed

Hodge, Lucy S; Downs, Levi S; Chura, Justin C; Thomas, Sajeena G; Callery, Patrick S; Soisson, A Patrick; Kramer, Paul; Wolfe, Stephen S; Tracy, Timothy S

2012-10-01

Chemoradiation is the mainstay of therapy for advanced cervical cancer, with the most effective treatment regimens involving combinations of radiosensitizing agents. However, administration of radiosensitizing chemotherapeutics concurrently with pelvic radiation is not without side effects. The aim of this study was to examine the utility of localized drug delivery as a means of improving drug targeting of radiosensitizing chemotherapeutics to the cervix while limiting systemic toxicities. An initial proof-of-concept study was performed in 14 healthy women following local administration of diazepam utilizing a novel cervical delivery device (CerviPrep™). Uterine vein and peripheral blood samples were collected and diazepam was measured using a GC-MS method. In the follow-up study, gemcitabine was applied to the cervix in 17 women undergoing hysterectomy for various gynecological malignancies. Cervical tissue, uterine vein blood samples, and peripheral plasma were collected, and gemcitabine and its deaminated metabolite 2',2'-difluorodeoxyuridine (dFdU) were measured using HPLC-UV and LC/MS methods. Targeted delivery of diazepam to the cervix was consistent with parent drug detectable in the uterine vein of 13 of 14 women. In the second study, pharmacologically relevant concentrations of gemcitabine (0.01-6.6 nmol/g tissue) were detected in the cervical tissue of 11 of 16 available specimens with dFdU measureable in 15 samples (0.04-8.8 nmol/g tissue). Neither gemcitabine nor its metabolites were detected in the peripheral plasma of any subject. Localized drug delivery to the cervix is possible and may be useful in limiting toxicity associated with intravenous administration of chemotherapeutics for radiosensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

Non-local electron transport validation using 2D DRACO simulations

NASA Astrophysics Data System (ADS)

Cao, Duc; Chenhall, Jeff; Moll, Eli; Prochaska, Alex; Moses, Gregory; Delettrez, Jacques; Collins, Tim

2012-10-01

Comparison of 2D DRACO simulations, using a modified versionfootnotetextprivate communications with M. Marinak and G. Zimmerman, LLNL. of the Schurtz, Nicolai and Busquet (SNB) algorithmfootnotetextSchurtz, Nicolai and Busquet, ``A nonlocal electron conduction model for multidimensional radiation hydrodynamics codes,'' Phys. Plasmas 7, 4238(2000). for non-local electron transport, with direct drive shock timing experimentsfootnotetextT. Boehly, et. al., ``Multiple spherically converging shock waves in liquid deuterium,'' Phys. Plasmas 18, 092706(2011). and with the Goncharov non-local modelfootnotetextV. Goncharov, et. al., ``Early stage of implosion in inertial confinement fusion: Shock timing and perturbation evolution,'' Phys. Plasmas 13, 012702(2006). in 1D LILAC will be presented. Addition of an improved SNB non-local electron transport algorithm in DRACO allows direct drive simulations with no need for an electron conduction flux limiter. Validation with shock timing experiments that mimic the laser pulse profile of direct drive ignition targets gives a higher confidence level in the predictive capability of the DRACO code. This research was supported by the University of Rochester Laboratory for Laser Energetics.

Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo.

PubMed

Heun, Yvonn; Hildebrand, Staffan; Heidsieck, Alexandra; Gleich, Bernhard; Anton, Martina; Pircher, Joachim; Ribeiro, Andrea; Mykhaylyk, Olga; Eberbeck, Dietmar; Wenzel, Daniela; Pfeifer, Alexander; Woernle, Markus; Krötz, Florian; Pohl, Ulrich; Mannell, Hanna

2017-01-01

In the field of vascular gene therapy, targeting systems are promising advancements to improve site-specificity of gene delivery. Here, we studied whether incorporation of magnetic nanoparticles (MNP) with different magnetic properties into ultrasound sensitive microbubbles may represent an efficient way to enable gene targeting in the vascular system after systemic application. Thus, we associated novel silicon oxide-coated magnetic nanoparticle containing microbubbles (SO-Mag MMB) with lentiviral particles carrying therapeutic genes and determined their physico-chemical as well as biological properties compared to MMB coated with polyethylenimine-coated magnetic nanoparticles (PEI-Mag MMB). While there were no differences between both MMB types concerning size and lentivirus binding, SO-Mag MMB exhibited superior characteristics regarding magnetic moment, magnetizability as well as transduction efficiency under static and flow conditions in vitro . Focal disruption of lentiviral SO-Mag MMB by ultrasound within isolated vessels exposed to an external magnetic field decisively improved localized VEGF expression in aortic endothelium ex vivo and enhanced the angiogenic response. Using the same system in vivo , we achieved a highly effective, site-specific lentiviral transgene expression in microvessels of the mouse dorsal skin after arterial injection. Thus, we established a novel lentiviral MMB technique, which has great potential towards site-directed vascular gene therapy.