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C T Moonen
Netherlands Institute for Space Research, Utrecht, Utrecht, Utrecht, Netherlands
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Available from: Chris Oerlemans
Rapid dynamic R1 /R2 */temperature assessment: a method with potential for monitoring drug delivery.
Cyril Lorenzato
Chris Oerlemans
Alexandru Cernicanu
Mario Ries
Baudouin Denis de Senneville
, Chrit Moonen,
Clemens Bos
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Local drug delivery by hyperthermia-induced drug release from thermosensitive liposomes (TSLs) may reduce the systemic toxicity of chemotherapy, whilst maintaining or increasing its efficacy. Relaxivity contrast agents can be co-encapsulated with the drug to allow the visualization of the presence of liposomes, by means of R2 *, as well as the co-release of the contrast agent and the drug, by means of R1, on heating. Here, the mathematical method used to extract both R2 * and R1 from a fast dynamic multi-echo spoiled gradient echo (ME-SPGR) is presented and analyzed. Finally, this method is used to monitor such release events. R2 * was obtained from a fit to the ME-SPGR data. Absolute R1 was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look-Locker R1 map. The method was used to monitor nearly homogeneous water bath heating and local focused ultrasound heating of muscle tissue, and to visualize the release of a gadolinium chelate from TSLs in vitro. R2 *, R1 and temperature maps were measured with a 5-s temporal resolution. Both R2 *and R1 measured were found to change with temperature. The dynamic R1 measurements after heating agreed with the Look-Locker R1 values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R1 increase near the phase transition temperature, as well as a shallow R2 * increase. Simultaneous temperature, R2 * and R1 mapping is feasible in real time and has the potential for use in image-guided drug delivery studies. Copyright © 2014 John Wiley & Sons, Ltd.
NMR in Biomedicine 09/2014;
· 3.45 Impact Factor
A Clinically Feasible Treatment Protocol for Magnetic Resonance-Guided High-Intensity Focused Ultrasound Ablation in the Liver.
Joost W Wijlemans
Martijn de Greef
Gerald Schubert
Lambertus W Bartels
, Chrit T W Moonen,
Maurice A A J van den Bosch
Mario Ries
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Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) allows for noninvasive thermal ablation under real-time temperature imaging guidance. The purpose of this study was to assess the feasibility and safety of MR-HIFU ablation of liver tissue in a clinically acceptable setting. The experimental protocol was designed with a clinical ablation procedure of a small malignant tumor in mind; the procedures were performed within a clinically feasible time frame and care was taken to avoid adverse events. The main outcome was the size and quality of the ablated liver tissue volume on imaging and histology. Secondary outcomes were safety and treatment time.
Investigative radiology. 09/2014;
Intrapleural Fluid Infusion for MR-Guided High-Intensity Focused Ultrasound Ablation in the Liver Dome
Joost W. Wijlemans
Martijn de Greef
Gerald Schubert
, Chrit T.W. Moonen,
Maurice A.A.J. van den Bosch
Mario Ries
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Rationale and Objectives Magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) ablation of tumors in the liver dome is challenging because of the presence of air in the costophrenic angle. In this study, we used a porcine liver model and a clinical MR-HIFU system to assess the feasibility and safety of using intrapleural fluid infusion (IPI) to create an acoustic window for MR-HIFU ablation in the liver dome. Materials and Methods Healthy adult Dalland land pigs (n = 6) under general anesthesia were used with animal committee approval. Degassed saline (200–800 mL) was infused into the intrapleural space under ultrasound guidance. A clinical 1.5-T MR-HIFU system was used to perform sonications (4-mm treatment cells, 300–450 W, 20–30 seconds) in the liver dome under real-time MR thermometry. An intercostal firing technique was used to prevent rib heating in one experiment. Technical success was defined as a temperature increase (>10°C) in the target area. After termination, the animal was examined for thermal damage to liver, diaphragm, pleura, lung, or intercostal muscle. Results An acoustic window was established in all animals. A temperature increase in the target area was achieved in all animals (max. 47°C–67°C). MR thermometry showed no heating outside the target area. Intercostal firing effectively reduced rib heating (55°C vs. 42°C). Postmortem examination revealed no unwanted thermal damage. One complication occurred, in the first experiment, because of an ill-suited needle (displacement of the needle). Conclusions The results indicate that IPI may be used safely to assist MR-HIFU ablation of tumors in the liver dome. For reliable tissue coagulation, IPI must be combined with an intercostal sonication technique. Considering the proportion of patients with tumors in the liver dome, IPI widens the applicability of MR-HIFU ablation for liver tumors considerably.
Academic Radiology 08/2014;
· 1.91 Impact Factor
Available from: Ine Lentacker
Ultrasound assisted drug delivery.
Chrit Moonen,
Ine Lentacker
Advanced drug delivery reviews 04/2014;
· 11.96 Impact Factor
Tracking of Cell Nuclei for Assessment of In Vitro Uptake Kinetics in Ultrasound-Mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy.
Marc Derieppe
Baudouin Denis de Senneville
Hugo Kuijf
, Chrit Moonen,
Clemens Bos
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Previously, we demonstrated the feasibility to monitor ultrasound-mediated uptake of a cell-impermeable model drug in real time with fibered confocal fluorescence microscopy. Here, we present a complete post-processing methodology, which corrects for cell displacements, to improve the accuracy of pharmacokinetic parameter estimation. Nucleus detection was performed based on the radial symmetry transform algorithm. Cell tracking used an iterative closest point approach. Pharmacokinetic parameters were calculated by fitting a two-compartment model to the time-intensity curves of individual cells. Cells were tracked successfully, improving time-intensity curve accuracy and pharmacokinetic parameter estimation. With tracking, 93 % of the 370 nuclei showed a fluorescence signal variation that was well-described by a two-compartment model. In addition, parameter distributions were narrower, thus increasing precision. Dedicated image analysis was implemented and enabled studying ultrasound-mediated model drug uptake kinetics in hundreds of cells per experiment, using fiber-based confocal fluorescence microscopy.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 02/2014;
· 2.47 Impact Factor
Available from: James R Baker
Assessing the barriers to image-guided drug delivery.
Gregory M Lanza
, Chrit Moonen,
James R Baker
Esther Chang
Zheng Cheng
Piotr Grodzinski
Katherine Ferrara
Kullervo Hynynen
Gary Kelloff
Yong-Eun Koo Lee
Anil K Patri
David Sept
Jan E Schnitzer
Bradford J Wood
Miqin Zhang
Gang Zheng
Keyvan Farahani
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Imaging has become a cornerstone for medical diagnosis and the guidance of patient management. A new field called image-guided drug delivery (IGDD) now combines the vast potential of the radiological sciences with the delivery of treatment and promises to fulfill the vision of personalized medicine. Whether imaging is used to deliver focused energy to drug-laden particles for enhanced, local drug release around tumors, or it is invoked in the context of nanoparticle-based agents to quantify distinctive biomarkers that could risk stratify patients for improved targeted drug delivery efficiency, the overarching goal of IGDD is to use imaging to maximize effective therapy in diseased tissues and to minimize systemic drug exposure in order to reduce toxicities. Over the last several years, innumerable reports and reviews covering the gamut of IGDD technologies have been published, but inadequate attention has been directed toward identifying and addressing the barriers limiting clinical translation. In this consensus opinion, the opportunities and challenges impacting the clinical realization of IGDD-based personalized medicine were discussed as a panel and recommendations were proffered to accelerate the field forward. WIREs Nanomed Nanobiotechnol 2014, 6:1-14. doi: 10.1002/wnan.1247 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.
Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 01/2014; 6(1):1-14.
· 5.68 Impact Factor
Available from: Merel Huisman
Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases.
Merel Huisman
Mie K Lam
Lambertus W Bartels
Robbert J Nijenhuis
, Chrit T Moonen,
Floor M Knuttel
Helena M Verkooijen
Marco van Vulpen
Maurice A van den Bosch
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Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has recently emerged as an effective treatment option for painful bone metastases. We describe here the first experience with volumetric MR-HIFU for palliative treatment of painful bone metastases and evaluate the technique on three levels: technical feasibility, safety, and initial effectiveness.
Journal of therapeutic ultrasound. 01/2014; 2:16.
Available from: Ine Lentacker
Understanding ultrasound induced sonoporation: definitions and underlying mechanisms.
I Lentacker
I De Cock
R Deckers
S C De Smedt
, C T W Moonen
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In the past two decades, research has underlined the potential of ultrasound and microbubbles to enhance drug delivery. However, there is less consensus on the biophysical and biological mechanisms leading to this enhanced delivery. Sonoporation, i.e. the formation of temporary pores in the cell membrane, as well as enhanced endocytosis is reported. Because of the variety of ultrasound settings used - and corresponding microbubble behavior, a clear overview is missing. Therefore, in this review, the mechanisms contributing to sonoporation are categorized according to three ultrasound settings: i) low intensity ultrasound leading to stable cavitation of microbubbles, ii) high intensity ultrasound leading to inertial cavitation with microbubble collapse, and iii) ultrasound application in the absence of microbubbles. Using low intensity ultrasound, the endocytotic uptake of several drugs could be stimulated, while short but intense ultrasound pulses can be applied to induce pore formation and the direct cytoplasmic uptake of drugs. Ultrasound intensities may be adapted to create pore sizes correlating with drug size. Small molecules are able to diffuse passively through small pores created by low intensity ultrasound treatment. However, delivery of larger drugs such as nanoparticles and gene complexes, will require higher ultrasound intensities in order to allow direct cytoplasmic entry.
Advanced drug delivery reviews 11/2013;
· 11.96 Impact Factor
In vivo T2 -based MR thermometry in adipose tissue layers for high-intensity focused ultrasound near-field monitoring.
Paul Baron
Mario Ries
Roel Deckers
Martijn de Greef
Jukka Tanttu
Max Köhler
Max A Viergever
, Chrit T W Moonen,
Lambertus W Bartels
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During MR-guided high-intensity focused ultrasound (HIFU) therapy, ultrasound absorption in the near field represents a safety risk and limits efficient energy deposition at the target. In this study, we investigated the feasibility of using T2 mapping to monitor the temperature change in subcutaneous adipose tissue layers. The T2 temperature dependence and reversibility was determined for fresh adipose porcine samples. The accuracy was evaluated by comparing T2 -based temperature measurements with probe readings in an ex vivo HIFU experiment. The in vivo feasibility of T2 -based thermometry was studied during HIFU ablations in the liver in pigs and of uterine fibroids in human patients. T2 changed linearly and reversibly with temperature with an average coefficient of 5.2 ± 0.1 ms/°C. For the ex vivo HIFU experiment, the difference between the T2 -based temperature change and the probe temperature was <0.9°C. All in vivo experiments showed temperature-related T2 changes in the near field directly after sonications. As expected, considerable intersubject variations in the cooling times were measured in the in vivo porcine experiments. The reversibility and linearity of the T2 -temperature dependence of adipose tissue allows for the monitoring of the temperature in the subcutaneous adipose tissue layers. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 11/2013;
· 3.27 Impact Factor
The Effects of Magnetic Resonance Imaging-guided High-Intensity Focused Ultrasound Ablation on human cadaver breast tissue.
Laura G Merckel
Roel Deckers
Paul Baron
Ronald L A W Bleys
Paul J van Diest
, Chrit T W Moonen,
Willem P Th M Mali
Maurice A A J van den Bosch
Lambertus W Bartels
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[Hide abstract]
Magnetic Resonance Imaging-guided High-Intensity Focused Ultrasound (MR-HIFU) is a promising technique for non-invasive breast tumor ablation. The purpose of this study was to investigate the effects of HIFU ablation and thermal exposure on ex vivo human breast tissue. HIFU ablations were performed in three unembalmed cadaveric breast specimens using a clinical MR-HIFU system. Sonications were performed in fibroglandular and adipose tissue. During HIFU ablation, time-resolved anatomical MR images were acquired to monitor macroscopic tissue changes. Furthermore, the breast tissue temperature was measured using a thermocouple to investigate heating and cooling under HIFU exposure. After HIFU ablation, breast tissue samples were excised and prepared for histopathological analysis. In addition, thermal exposure experiments were performed to distinguish between different levels of thermal damage using immunohistochemical staining. Irreversible macroscopic deformations up to 3.7mm were observed upon HIFU ablation both in fibroglandular and in adipose tissue. No relationship was found between the sonication power or the maximum tissue temperature and the size of the deformations. Temperature measurements after HIFU ablation showed a slow decline in breast tissue temperature. Histopathological analysis of sonicated regions demonstrated ablated tissue and morphologically complete cell death. After thermal exposure, samples exposed to three different temperatures could readily be distinguished. In conclusion, the irreversible macroscopic tissue deformations in ex vivo human breast tissue observed during HIFU ablation suggest that it might be relevant to monitor tissue deformations during MR-HIFU treatments. Furthermore, the slow decrease in breast tissue temperature after HIFU ablation increases the risk of heat accumulation between successive sonications. Since cell death was inflicted after already 5minutes at 75°C, MR-HIFU may find a place in non-invasive treatment of breast tumors.
European journal of pharmacology 04/2013;
· 2.59 Impact Factor
Quantitative Evaluation of Ultrasound-Mediated Cellular Uptake of a Fluorescent Model Drug.
Matthieu Lepetit-Coiffé
Anna Yudina
Christel Poujol
Philippe Lourenco de Oliveira
Franck Couillaud
, Chrit T W Moonen
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PURPOSE: This study aims to quantitatively analyze cellular uptake following local ultrasound (US)-mediated cell permeabilization. PROCEDURES: A 2 μM cell-impermeable dye Sytox Green was co-injected with 3 × 107 microbubbles in the presence of C6 rat glioblastoma cell monolayer in total volume of 10 ml. A 5.8-mm diameter mono-element US transducer was positioned at a distance of 8 mm to the Opticell® membrane. Acoustical pressure of pulsed US was varied from 0.62 MPa peak-to-peak (p-p) to 1.25 MPa p-p. Large field of view (FOV = 15 × 15 mm) 22 × 22 mosaic acquisitions were done under epifluorescence Leica DMR microscope and analyzed in Metamorph software to evaluate cell density as well as model drug uptake percentage. RESULTS: The size of acoustical field of the transducer closely matches the spatial pattern of the model drug internalized into the cells by US. Maximum of uptake percentage (42 ± 15 %) was found at 0.88 MPa p-p. CONCLUSIONS: Spatial aspect of US-mediated model drug uptake has been quantitatively evaluated on adherent cells using robust 2D-mapping approach.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 03/2013;
· 2.47 Impact Factor
MRI contrast variation of thermosensitive magnetoliposomes triggered by focused ultrasound: a tool for image-guided local drug delivery.
Cyril Lorenzato
Alexandru Cernicanu
Marie-Edith Meyre
Matthieu Germain
Agnès Pottier
Laurent Levy
Baudouin Denis de Senneville
Clemens Bos
, Chrit Moonen,
Pierre Smirnov
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Improved drug delivery control during chemotherapy has the potential to increase the therapeutic index. MRI contrast agent such as iron oxide nanoparticles can be co-encapsulated with drugs in nanocarrier liposomes allowing their tracking and/or visualization by MRI. Furthermore, the combination of a thermosensitive liposomal formulation with an external source of heat such as high intensity focused ultrasound guided by MR temperature mapping allows the controlled local release of the content of the liposome. MRI-guided high-intensity focused ultrasound (HIFU), in combination represents a noninvasive technique to generate local hyperthermia for drug release. In this study we used ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) encapsulated in thermosensitive liposomes to obtain thermosensitive magnetoliposomes (TSM). The transverse and longitudinal relaxivities of this MRI contrast agent were measured upon TSM membrane phase transition in vitro using a water bath or HIFU. The results showed significant differences for MRI signal enhancement and relaxivities before and after heating, which were absent for nonthermosensitive liposomes and free nanoparticles used as controls. Thus, incorporation of USPIO as MRI contrast agents into thermosensitive liposomes should, besides TSM tumor accumulation monitoring, allow the visualization of TSM membrane phase transition upon temperature elevation. In conclusion, HIFU under MR image guidance in combination with USPIO-loaded thermosensitive liposomes as drug delivery system has the potential for a better control of drug delivery and to increase the drug therapeutic index. Copyright © 2012 John Wiley & Sons, Ltd.
Contrast Media & Molecular Imaging 03/2013; 8(2):185-92.
· 2.87 Impact Factor
Evolution of the Ablation Region After Magnetic Resonance-Guided High-Intensity Focused Ultrasound Ablation in a Vx2 Tumor Model.
Joost W Wijlemans
Roel Deckers
Maurice A A J van den Bosch
Beatrijs A Seinstra
Marijn van Stralen
Paul J van Diest
, Chrit T W Moonen,
Lambertus W Bartels
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[Hide abstract]
OBJECTIVES: Volumetric magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) is a completely noninvasive image-guided thermal ablation technique. Recently, there has been growing interest in the use of MR-HIFU for noninvasive ablation of malignant tumors. Of particular interest for noninvasive ablation of malignant tumors is reliable treatment monitoring and evaluation of response. At this point, there is limited evidence on the evolution of the ablation region after MR-HIFU treatment. The purpose of the present study was to comprehensively characterize the evolution of the ablation region after volumetric MR-HIFU ablation in a Vx2 tumor model using MR imaging, MR temperature data, and histological data. MATERIALS AND METHODS: Vx2 tumors in the hind limb muscle of New Zealand White rabbits (n = 30) were ablated using a clinical MR-HIFU system. Twenty-four animals were available for analyses. Magnetic resonance imaging was performed before and immediately after ablation; MR temperature mapping was performed during the ablation. The animals were distributed over 7 groups with different follow-up lengths. Depending on the group, animals were reimaged and then killed on day 0, 1, 3, 7, 14, 21, or 28 after ablation. For all time points, the size of nonperfused areas (NPAs) on contrast-enhanced T1-weighted (CE-T1-w) images was compared with lethal thermal dose areas (ie, the tissue area that received a thermal dose of 240 equivalent minutes or greater [EM] at 43°C) and with the necrotic tissue areas on histology sections. RESULTS: The NPA on CE-T1-w imaging showed an increase in median size from 266 ± 148 to 392 ± 178 mm during the first day and to 343 ± 170 mm on day 3, followed by a gradual decrease to 113 ± 103 mm on day 28. Immediately after ablation, the NPA was 1.6 ± 1.4 times larger than the area that received a thermal dose of 240 EM or greater in all animals. The median size of the necrotic area on histology was 1.7 ± 0.4 times larger than the NPA immediately after ablation. After 7 days, the size of the NPA was in agreement with the necrotic tissue area on histology (ratio, 1.0 ± 0.2). CONCLUSIONS: During the first 3 days after MR-HIFU ablation, the ablation region increases in size, after which it gradually decreases in size. The NPA on CE-T1-w imaging underestimates the extent of tissue necrosis on histology in the initial few days, but after 1 week, the NPA is reliable in delineating the necrotic tissue area. The 240-EM thermal dose limit underestimates the necrotic tissue area immediately after MR-HIFU ablation. Reliable treatment evaluation techniques are particularly important for noninvasive, image-guided tumor ablation. Our results indicate that CE-T1-w imaging is reliable for MR-HIFU treatment evaluation after 1 week.
Investigative radiology 02/2013;
· 4.85 Impact Factor
Available from: Lisbeth Van ruijssevelt
Observations on the viability of C6-glioma cells after sonoporation with low-intensity ultrasound and microbubbles.
Lisbeth Ruijssevelt
Pierre Smirnov
Anna Yudina
Veronique Bouchaud
Pierre Voisin
, Chrit Moonen
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[Hide abstract]
Ultrasound (US) and microbubbles can be used to facilitate cellular uptake of drugs through a cavitationinduced enhancement of cell membrane permeability. The mechanism is, however, still incompletely understood. A direct contact between microbubbles and cell membrane is thought to be essential to create membrane perturbations lasting from seconds to minutes after US exposure of the cells. A recent study showed that the effect may even last up to 8 h after cavitation (with residual permeability up to 24 h after cavitation). In view of possible membrane damage, the purpose of this study was to further investigate the evolution of cell viability in the range of the 24-h temporal window. Furthermore, a description of the functional changes in tumor cells after US exposure was initiated to obtain a better understanding of the mechanism of membrane perturbation after sonication with microbubbles. Our results suggest that US does not reduce cell viability up to 24 h post-exposure. However, a perturbation of the entire cell population exposed to US was observed in terms of enzymatic activity and characteristics of the mitochondrial membrane. Furthermore, we demonstrated that US cavitation induces a transient loss of cell membrane asymmetry, resulting in phosphatidylserine exposure in the outer leaflet of the cell membrane.
IEEE transactions on ultrasonics, ferroelectrics, and frequency control 01/2013; 60(1):34-45.
· 1.80 Impact Factor
Conference Paper:
Real-time anticipation of organ displacement for MR-guidance of interventional procedures
B.D. de Senneville
M. Ries
, C.T.W. Moonen
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Modern Magnetic Resonance Imaging (MRI) methods now allow the rapid acquisition of images with an excellent tissue contrast and high spatial resolution. Complex organ deformations can thus be estimated using image registration techniques applied to anatomical information. This opens great perspectives for the use of MRI to retroactively target an interventional procedure in mobile organs in real-time. For this purpose, both the update time and the latency of the motion information are two key points. In the current paper, the organ deformation is estimated on a voxel-by-voxel basis and a Kalman predictor is used to compensate for the residual latency. The implementation benefitted from the parallel architecture of Graphical Processing Units (GPU) for accelerating computation times. The efficiency and the potential of the method to anticipate organ displacements in real-time was evaluated on the abdomen of twelve free-breathing volunteers. The deformation of both kidney and liver could be updated with a rate of 10 Hz over sustained periods of several minutes, and the employed Kalman predictor reduced the tracking error in average by 30%.
Biomedical Imaging (ISBI), 2013 IEEE 10th International Symposium on; 01/2013
Extended Kalman Filtering for continuous volumetric MR-Temperature Imaging.
B Denis de Senneville
S Roujol
S Hey
, C Moonen,
M Ries
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Real time magnetic resonance (MR) thermometry has evolved into the method of choice for the guidance of highintensity focused ultrasound (HIFU) interventions. For this role, MR-thermometry should preferably have a high temporal and spatial resolution and allow observing the temperature over the entire targeted area and its vicinity with a high accuracy. In addition, the precision of real time MR-thermometry for therapy guidance is generally limited by the available Signal to Noise ratio (SNR) and the influence of physiological noise. MR-guided HIFU would benefit of the large coverage volumetric temperature maps, including characterization of volumetric heating trajectories as well as near- and far-field heating. In this paper, continuous volumetric MR-temperature monitoring was obtained as follows: The targeted area was continuously scanned during the heating process by a multi-slice sequence. Measured data and a priori knowledge of 3D data derived from a forecast based on a physical model were combined using an Extended Kalman Filter (EKF). The proposed reconstruction improved the temperature measurement resolution and precision while maintaining guaranteed output accuracy. The method was evaluated experimentally ex-vivo on a phantom, and in-vivo on a porcine kidney, using HIFU heating. On the in-vivo experiment, it allowed the reconstruction from a spatio-temporally under-sampled data set (with an update rate for each voxel of 1.143 s) to a 3D dataset covering a field of view of 142.528554 mm3 with a voxel size of 336 mm3 and a temporal resolution of 0.127 s. The method also provided noise reduction, while having a minimal impact on accuracy and latency.
IEEE transactions on medical imaging. 12/2012;
MR-Guided High-Intensity Focused Ultrasound Ablation of Breast Cancer with a Dedicated Breast Platform.
Laura G Merckel
Lambertus W Bartels
Max O Köhler
H J G Desirée van den Bongard
Roel Deckers
Willem P Th M Mali
Christoph A Binkert
, Chrit T Moonen,
Kenneth G A Gilhuijs
Maurice A A J van den Bosch
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[Hide abstract]
Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.
CardioVascular and Interventional Radiology 12/2012;
· 2.09 Impact Factor
Combined magnetic resonance imaging and ultrasound echography guidance for motion compensated HIFU interventions
Mario Ries
Baudouin Denis de Senneville
Yvan Regard
, Chrit Moonen
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The objective of this study is to evaluate the feasibility to integrate ultrasound echography as an additional imaging modality for continuous target tracking, while performing simultaneously real-time MR- thermometry to guide a High Intensity Focused Ultrasound (HIFU) ablation. Experiments on a moving phantom were performed with MRI-guided HIFU during continuous ultrasound echography. Real-time US echography-based target tracking during MR-guided HIFU heating was performed with heated area dimensions similar to those obtained for a static target. The combination of both imaging modalities shows great potential for real-time beam steering and MR-thermometry.
Large aperture transducer designed for MR-HIFU treatment of breast tumors
C. Mougenot
M. Köhler
M. Tillander
, C. Moonen,
L. W. Bartels
G. Ehnholm
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[Hide abstract]
A novel large aperture transducer design is proposed for MR-HIFU treatment of breast tumors. The phased array is composed of 384 elements placed on a circular structure with a lateral beam direction. This beam path orientation considerably reduces the risk of damaging nearby vital organs. In addition, this transducer shape induces a well delineated sharp focal point with low energy density in the near and far field for safe, accurate and efficient treatment. The performance of the transducer is demonstrated with acoustic field measurements and temperature maps of a phantom sonication.
Real-Time Assessment of Ultrasound-Mediated Drug Delivery Using Fibered Confocal Fluorescence Microscopy.
Marc Derieppe
Anna Yudina
Matthieu Lepetit-Coiffé
Baudouin Denis de Senneville
Clemens Bos
, Chrit Moonen
[Show abstract]
[Hide abstract]
PURPOSE: Transport across the plasma membrane is a critical step of drug delivery for weakly permeable compounds with intracellular mode of action. The purpose of this study is to demonstrate real-time monitoring of ultrasound (US)-mediated cell-impermeable model drug uptake with fibered confocal fluorescence microscopy (FCFM). PROCEDURES: An in vitro setup was designed to combine a mono-element US transducer, a cell chamber with a monolayer of tumor cells together with SonoVue microbubbles, and a FCFM system. The cell-impermeable intercalating dye, SYTOX Green, was used to monitor US-mediated uptake. RESULTS: The majority of the cell population showed fluorescence signal enhancement 10 s after US onset. The mean rate constant k of signal enhancement was calculated to be 0.23 ± 0.04 min(-1). CONCLUSIONS: Feasibility of real-time monitoring of US-mediated intracellular delivery by FCFM has been demonstrated. The method allowed quantitative assessment of model drug uptake, holding great promise for further local drug delivery studies.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 06/2012;
· 2.47 Impact Factor
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Bruno Quesson
French National Centre for Scientific Research
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Baudouin Denis de Senneville
French National Centre for Scientific Research
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Mario Ries
Utrecht University
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Peter van zijl
Johns Hopkins University
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Franz Müller
University of Georgia
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Magnetic Resonance in Medicine
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Netherlands Institute for Space Research, Utrecht
Utrecht, Utrecht, Netherlands
University Medical Center Utrecht
Image Sciences Institute
Utrecht, Utrecht, Netherlands
Ghent University
Department of Pharmaceutics
Gand, Flanders, Belgium
Université Victor Segalen Bordeaux 2
Centre de Résonance Magnétique des Systèmes Biologiques
Burdeos, Aquitaine, France
Eindhoven, North Brabant, Netherlands
University of Bordeaux
Burdeos, Aquitaine, France
National Institutes of Health
• Division of Functional and Molecular Imaging
• Laboratory of Research Technologies
• Office of Intramural Research
Bethesda, MD, United States
Maryland, United States
French National Centre for Scientific Research
Lutetia Parisorum, Île-de-France, France
University of Illinois at Chicago
Chicago, Illinois, United States
Aarhus University Hospital
Institute of Clinical Medicine
Aarhus, Central Jutland, Denmark
Unité Inserm U1077
Caen, Lower Normandy, France
Centre Hospitalier Universitaire de Bordeaux
Burdeos, Aquitaine, France
French Institute of Health and Medical Research
Lutetia Parisorum, Île-de-France, France
National Institute of Mental Health (NIMH)
Clinical Brain Disorders Branch
Bethesda, MD, United States
Royal College of Surgeons of England
Londinium, England, United Kingdom
Georgetown University
Department of Pharmacology
Rockville, MD, United States
Center for Magnetic Resonance Research Minnesota, USA
Minneapolis, Minnesota, United States
Delft University of Technology
Applied Geophysics and Petrophysics
Delft, South Holland, Netherlands
Wageningen University
Laboratory of Biochemistry
Wageningen, Provincie Gelderland, Netherlands
National Institute on Alcohol Abuse and Alcoholism
Maryland, United States
National Eye Institute
Maryland, United States
Semmelweis University
Budapeŝto, Budapest, Hungary
Medical Physics
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World Cup organisers deny venue shortlist
ESPN Staff
March 3, 2013
The Olympic Stadium in Stratford appears unlikely to be part of 2015 Rugby World Cup © Getty Images
Reported World Cup venues:
Organisers for the 2015 Rugby World Cup have said reports claiming to list the 12 finalised venues for the tournament were "not at all true".
Reports this morning suggested the venues for rugby's showpiece had already been agreed upon and that only three of them would be traditional rugby stadiums. Organisers have, however, described the reported list as inaccurate with a final decision not due to be announced until later this month.
"That list is not at all true. It is entirely speculation," a spokesman for the 2015 Rugby World Cup said. "It is not the final list."
A long list of 17 venues was announced in October last year with five due to be cut when this month's final announcement is made. The only rugby stadiums in that long list were the three named in this morning's reports - Twickenham, the Millennium Stadium and Gloucester's Kingsholm ground.
The remaining venues, apart from the Olympic Stadium in Stratford, are football grounds. The Olympic Stadium appears unlikely to be one of the 12 confirmed venues with this morning's reports matching previous suggestions that the venue would not be available.
"The long-list has been in the public domain for a long time," the spokesman said. "The use of football stadiums was a part of the bid which was well documented."
Second-tier football club Leicester City's King Power Stadium is among the long list of venues but Aviva Premiership high-fliers Leicester Tigers' nearby Welford Road home was overlooked. Other high-capacity football venues included are Wembley, Old Trafford and St James' Park.
© ESPN Sports Media Ltd.
|Live Scores
The greatest fly-half of them all
Following the passing of Jack Kyle, Huw Richards pays tribute to arguably the finest player Ireland has produced
The Battle of Ballymore revisited
"When Mike Burton was sent off I thought the world had gone crazy - just Pommy bashing, hitting anyone." Behind the Rose heads back to 1975
The time for tinkering is over - England must nail their colours to the mast in key positions, writes Phil Vickery
Gatland should learn from Joe Schmidt
"New Zealand-born Joe Schmidt has forged the Irish into a street-smart, well- prepared side," John Mitchell on the Irish renaissance

subset: commoncrawl


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Boracay, Philippines
Newcoast, Yapak, Malay, Aklan, 5608 Boracay, Philippines – Show map
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222 properties in Boracay
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Fairways and Bluewater Newcoast Boracay's staff speaks: Filipino, English
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Outdoor Pool (all year), Grounds, Terrace
Golf Course (within 2 miles), Horseback Riding, Sauna, Fitness Center, Spa, Massage, Hot Tub, Private Beach Area
Food & Drink
Bar, Restaurant with Dining Menu, Buffet-Style Restaurant
WiFi is available in all areas and charges apply.
Free public parking is available on site (reservation is needed).
Room Service, Shuttle Service (surcharge), Airport Shuttle (surcharge), 24-Hour Front Desk, Tour Desk, Baggage Storage, Concierge Service, Laundry, Meeting/Banquet Facilities, Fax/Photocopying
Newspapers, Chapel/Shrine, Non-smoking Rooms, Family Rooms
Filipino, English
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Children and Extra Beds
All children are welcome.
One child from 0 to 6 years stays free of charge when using existing beds.
One child from 7 to 11 years is charged PHP 200 per person per night when using existing beds.
One older child or adult is charged PHP 1500 per person per night in an extra bed.
The maximum number of extra beds in a room is 1.
There is no capacity for cribs in the room.
Any type of extra bed or crib is upon request and needs to be confirmed by management.
Additional fees are not calculated automatically in the total cost and will have to be paid for separately during your stay.
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Red Coconut Beach Hotel Boracay
Villa Caemilla Beach Boutique HotelWelcoming guests with a private beach area situated along White Beach, the Villa Caemilla Beach Boutique Hotel features luxuriously furnished rooms equipped with free Wi-Fi access.
Score from 314 reviews Excellent
Ambassador In Paradise is on the beautiful sands of Boracay Island offering views of the ocean. The resort features a restaurant, beachside pool and rooms with balconies and free Wi-Fi.
Score from 229 reviews Very good
Boracay Regency Beach Resort & SpaSteps from the white sands of Boracay Beach, Boracay Regency Resort enjoys a prime beachfront location, a 5-minute walk from D'Mall. It features 3 outdoor pools and 7 dining options.
Score from 45 reviews Very good
On a hill, the Hotel Soffia features spectacular views of the ocean. It provides free Wi-Fi, an outdoor pool and free shuttle services to White Beach.
Score from 185 reviews Good
Wi-Fi charge 100 peso. Luckily I didn't pay. There's no signal at all or very weak. Others are really great
Very friendly and accommodating staff. Fast & Great service. Unlimited shuttle service. Beautiful infinity pool and private Beach. Good buffet breakfast. Highly recommended! (Traveled Nov. 23-25, 2014)
Good Breakfast Nice pool areas with bars Clean rooms Free shuttle service
No free internet
Rooms are nice and clean
Good hotel, super staff
On the breakfest not any ham and chesse. Beach is dirty. ..
Polite personal, good breakfast
Hotel's beach
We just married. Have choosen this hotel because of the territory. It was big mistake. Territory is nice, hotel is good and staff was friendly. But next morning we came and decided to make some photos for us near pool and beach in wedding dress (no ceremony, nothing commercial, just for private use) hotel didn't allow us to do this. They asked for 5000 PHP per location. We thought this is a joke, as we paid already for room. When we checked out, reception asked for this payment. I refused and asked for manager, but he never come. After 1 hour arguing hotel offered 50% discount and promised, that manager will contact me. Manager never replied, unfortunatelly. So, i suggest do not stay in this hotel, there are a lot of other places with realistic rules and better managers!!!
Food, environment, staff, beach
Excess room charges are not fair. Considering I have infant and child with us.
Golf course , beach , staff .
Price of poor Wi-Fi !! Price of hire of very poor golf equipement , paying cash for food & drink , getting to the resort !!!
- good breakfast
- hidden fees, final price paid was around 25% more than what was shown in booking.com search results - scam-like cancellation policy (no matter how early you cancel you lose 100% for ALL the nights!) - the main swimming pool was closed "for maintenance" for a week with no sign of any work being done
The safety and security of the hotel. The shuttle buses to dmall was good and frequent.
Taking the shuttle each time we had to go for breakfast or a swim.
Their were helpful staff everywhere. All very friendly and knowledgeable. It made getting to specific places on time very easy. Loved the environment and friendly atmosphere
Friendly helpful staff Location Beaches Horse riding Swimming pools
Limited dining options
staff are nice, and the bedroom was really comfortable and clean. the shuttle was always at the mall on time. good value for money.
it is a bit distant from the main area, that is why it is very convenient the shuttle they provide
Great location
Wifi should be free for the price you pay for the room. Also only 1 device can be connected Per payment which is annoying.
i loved everything about this hotel. i will surely go back and recommend this.
Beautiful beach and good facilities
Be careful if you book last minute because the hotel will not offer hotel transfers unless you book a certain amount of time in advance. Also there is no ATM in the hotel and food and drinks in certain bars can not be charged to the room.
One hundred pesos a day for each device used didn't seem right and the shuttle to the beach could be a real pain ended up finding my own way back most of the time
Very relaxing, great breakfast, nice rooms. Excellent staff
shuttle service free; securitys very nice and competent
breakfast not continental standard, spa only for mans, ignored the asking for pick up from airport, third party payment is not accepted
Staff were always attentive and courteous.
There were mosquitoes.
No coordination with reservation and front desk....
-the staff is courteous, friendly and helpful -pools are great -it has its own beachfront -we feel secured because of the security people scattered all around the compound -we enjoyed the privacy and the perfect ambiance -good value for our money!
-it took us a while to check-out, we were left behind by the shuttle because of this and made to wait for another hour for the next one -
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text: Celsion Company Profile (NASDAQ:CLSN) Tweet Analyst RatingsEarningsDividendsInsider TradesCompany ProfileSocial ActivityToday's Chart Consensus Ratings for Celsion (NASDAQ:CLSN) (?) The ratings breakdown includes the most recent rating from each analyst that has rated the stock within the last twelve months. The ratings score is a calculation of the average number of sell, hold, buy and strong buy ratings (0-1.5 = Sell, 1.5-2.5 = Hold, 2.5-3.5 = Buy, >3.5 = Strong Buy). The consensus price target is a mean average of the most recent price target set by each analyst that has set a price target for the stock in the last twelve months.Ratings Breakdown: 4 Buy Rating(s)Consensus Rating:Buy (Score: 3.00)Consensus Price Target: $8.88 (232.40% upside) Analysts' Ratings History for Celsion (NASDAQ:CLSN) Show: All Ratings For This Stock Only the Most Recent Rating From Each Brokerage DateFirmActionRatingPrice TargetDetailsShare10/30/2014Canaccord GenuityInitiated CoverageBuy$7.00View 10/30/2014Cantor FitzgeraldInitiated CoverageBuy$7.00View 7/17/2014Paradigm CapitalBoost Price TargetBuy$12.50 -> $13.50View 1/10/2014HC WainrightInitiated CoverageBuy$5.00 -> $8.00View 5/10/2013Roth CapitalLower Price TargetNeutral$1.70 -> $1.00View 1/31/2013Roth CapitalDowngradeBuy -> Neutral$10.00 -> $1.70View 1/17/2013Brean CapitalDowngradeHold -> Sell$7.00 -> $1.00View 1/16/2013Roth CapitalReiterated RatingBuyView 11/27/2012Dawson JamesInitiated CoverageOutperform$9.00View (Data available from 11/25/2012 forward) Earnings History for Celsion (NASDAQ:CLSN)DateQuarterConsensus EstimateActual EPSRevenue EstimateActual RevenueRelease LinkConference CallDetailsShare11/12/2014($0.30)($0.35)ViewN/AView 8/7/2014Q214($0.32)($0.38)ViewN/AView 5/8/2014($0.24)($0.33)ViewN/AView 3/13/2014($0.28)($0.19)ViewN/AView 11/12/2013Q3($0.23)($0.30)$0.13 millionViewListenView 8/8/2013Q2 2013($0.07)$0.01$0.13 millionViewN/AView 5/9/2013Q1 2013($0.16)($0.12)ViewN/AView 11/12/2012Q312($0.17)($0.18)ViewN/AView (Data available from 1/1/2011 forward) Dividend History for Celsion (NASDAQ:CLSN)No dividend announcements for this company have been tracked by Analyst Ratings Network Insider Trading History for Celsion (NASDAQ:CLSN)Transaction DateInsider NameTitleBuy/SellNumber of SharesAverage Share PriceTotal TransactionSEC LinkShare11/13/2014Robert W HooperDirectorBuy4,000$2.50$10,000.00View 8/15/2014Alberto R Martinez JrDirectorBuy5,000$3.12$15,600.00View 8/15/2014Michael H TardugnoCEOBuy4,000$3.12$12,480.00View 8/14/2014Frederick J FritzDirectorBuy4,000$3.20$12,800.00View 6/26/2014Alberto R Martinez JrDirectorBuy5,000$3.36$16,800.00View 6/11/2014Michael H TardugnoCEOBuy5,000$3.20$16,000.00View 3/14/2014Frederick FritzDirectorBuy2,500$3.86$9,650.00View 3/14/2014Michael TardugnoCEOBuy4,000$3.84$15,360.00View 11/19/2013Michael TardugnoCEOBuy2,800$3.59$10,052.00View 11/15/2013Frederick FritzDirectorBuy3,000$3.80$11,400.00View 8/16/2013Frederick FritzDirectorBuy10,000$1.09$10,900.00View 8/16/2013Michael TardugnoCEOBuy5,000$1.08$5,400.00View 6/12/2013Michael H TardugnoCEOBuy10,000$1.35$13,500.00View 5/21/2013Alberto R Martinez JrDirectorBuy5,000$0.93$4,650.00View 5/13/2013Alberto R Martinez JrDirectorBuy5,000$0.96$4,800.00View 5/10/2013Alberto R Martinez JrDirectorBuy5,000$0.92$4,600.00View 3/20/2013Alberto R Martinez JrDirectorBuy3,750$1.06$3,975.00View 12/10/2012Max LinkDirectorBuy14,000$7.60$106,400.00View 11/15/2012Robert W HooperDirectorBuy11,600$5.20$60,320.00View 9/14/2012Michael H TardugnoCEOBuy5,000$5.03$25,150.00View 9/10/2012Robert W HooperDirectorBuy10,000$4.95$49,500.00View 8/29/2012Robert W HooperDirectorBuy2,500$4.65$11,625.00View (Data available from 1/1/2013 forward) About Celsion Celsion Corporation is an oncology drug development company focused on the development of treatments for those suffering with difficult to treat forms of cancer. As of December 31, 2011, the Company's product ThermoDox is being evaluated in a Phase III clinical trial for primary liver cancer (the HEAT study), a Phase II clinical trial for colorectal liver metastasis (CRLM) and a Phase II clinical trial for recurrent chest wall breast cancer. ThermoDox is a liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a range of cancers. Localized heat at mild hyperthermia temperatures releases the encapsulated doxorubicin from the liposome enabling high concentrations of doxorubicin to be deposited preferentially in and around the targeted tumor. In June 2014, it acquired all of the assets of EGEN Inc. Headlines: (10/30) Canaccord Genuity Initiates Coverage on Celsion (CLSN) - Ticker Report (11/3) Celsion Receives New Coverage from Analysts at Canaccord Genuity (CLSN) - sleekmoney (11/20) Celsion's Prospects For A Significant Upside Just Got A Lot Better (CLSN) - Seeking Alpha (11/18) Celsion Hits New 12-Month Low at $2.38 (CLSN) - WKRB News (11/13) Celsion (CLSN) Announces Quarterly Earnings, Misses Expectations By $0.05 ... - sleekmoney (11/12) Celsion (CLSN) Announces Quarterly Earnings, Misses Estimates By $0.05 EPS - WKRB News (11/21) Closing Bell Top Gainers: Celsion Corp. (CLSN), Crestwood Equity Partners LP ... - WallStreet Scope (11/6) Hot Stock List: Cisco Systems, Inc. (NASDAQ:CSCO), Celsion Corp. (NASDAQ ... - Street Newswire (registration) (11/5) Celsion Corporation Receives VHP Approval to Initiate OPTIMA Study in Europe - PR Newswire (press release) (10/29) Celsion Presents Preclinical Data for its TheraSilence™ Platform at the miRNA ... - MarketWatch Industry, Sector and Symbol: Sector: N/A Industry: N/A Sub-Industry: N/A Exchange: NASDAQ Symbol: CLSN CUSIP: Key Metrics: Previous Close: $2.6850 Day Moving Average: $2.5781200 Day Moving Average: $3.0312P/E Ratio: N/AP/E Growth: N/AMarket Cap: $53.3MCurrent Quarter EPS Consensus Estimate: $-1.43 EPS Additional Links: View CLSN on Google FinanceView CLSN on Yahoo FinanceView CLSN's Company Profile on ReutersSearch for Celsion Co. on Google Celsion (NASDAQ:CLSN) Chart for Tuesday, November, 25, 2014 (Chart Provided by Yahoo Finance)


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text:
Miracle Mile - STRFKR
User Score
Generally favorable reviews- based on 11 Ratings
User score distribution:
Positive: 9 out of 11
Mixed: 1 out of 11
Negative: 1 out of 11
Review this album
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Feb 25, 2013I do round down hence the 8. It is about an 8.4 for me but yeahh... all in all Strfkr (or for some of you older fans), bring us a good album which at times is very danceable but at other times is also slow paced. Some fans might not be keen to this new style but I personally think it works. As early as hearing "beach monster" we find out that Strfkr are trying to reach new horizons. "Golden Night" and "Nite Rite" also show a change of pace in their songs. Golden Light has a melancholic sound all throughout while Nite Rite although long and repetitive, works, and is among the strongest songs. The only negative to me is the length. Some songs which I do not consider the strongest, carry on for too long, and others which I like more are too short, but that varies on the person's music taste of course. I'm still not sure if this album is better than their previous album "Reptilians," but it definitely is a great listen if you want to listen to an album which can be danceable yet slowed down at times.… Expand
Apr 2, 2013STRFKR's best album so far, with Reptilians coming in at a close second, these guys keep on getting better and better, this album is packed with 15 songs, and there is not a forgettable one. On Miracle Mile it is becoming clear that the band is moving into a new style and going in a new direction, yes not all of the songs on this album are the danceable joyful songs that we know them for, but instead they are going for more of an Alternative Rock feel, there still are those dance songs that we all know and love, but the other songs such as Golden Light and Nite Rite, really stand out with the new style they are going for and those are two of the best songs on the whole album. This is an amazing album by STRFKR and their best yet.… Collapse
Apr 3, 2013It's hard to tell if the first half of Miracle Mile is really better than the first, or whether it's just that a kind of boredom sets in at some point during a listen, whether it's your first or your fifth.
Mar 22, 2013Miracle Mile masks its doom-and-gloom lyricism with so much danceability that it plays out with excess optimism. [Mar-Apr 2013, p.102]
Mar 20, 2013Miracle Mile is fun, but the record's sparse highs also lay bare its lows.


text:
Goodreads helps you keep track of books you want to read.
Start by marking "Give Me Back My Pony (Pony Pals, #4)" as Want to Read:
Give Me Back My Pony (Pony Pals #4)
Lulu must give the beautiful pony she's rescued and cared for back to its mean, snobby owner...unless the Pony Pals can come up with a plan.
Hardcover, 82 pages
Published May 1st 1995 by Turtleback Books
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Community Reviews
(showing 1-30 of 678)
Jul 23, 2008 Kayla rated it 5 of 5 stars · review of another edition
Recommends it for: Totally yah!!!!!
Recommended to Kayla by: No one
This book is great. You should read it. It is about a girl named Lulu and she took care of a girl named Rema's horse while Rema was at boarding school. When Rema came back from boarding school she blamed every thing on Lulu such as how she was not good at riding any more. You shouls totally read this book!!!!!!!!!!!!!!!!
Jul 09, 2012 Kristine Pratt rated it 3 of 5 stars · review of another edition
We all knew the day was coming where Lulu would have to give back the pony and go off with her dad. How the Pony Pals handle it is interesting and creative as usual. A fun book, not all the great, but still a good way to pass the time.
was an awesome book should read the whole series!
Aug 08, 2012 Meredith rated it 5 of 5 stars · review of another edition
Shelves: jeanne-betancourt, pony-pals
Very good book.
Sep 11, 2010 Amanda rated it 5 of 5 stars · review of another edition
Shelves: books-i-own, horses-unicorns-pegasus
Liked it!
|last activity
|This Book Is Great
|Jun 30, 2011 03:07PM
When I was growing up I never thought of being an author. I was a terrible speller and didn't want to write any more than I had to. I wanted to be a tap dancer when I grew up. After a few years of teaching junior high and high school, I wrote my first novel. It was a surprise to discover that I liked making up stories and writing them down. I liked it so much that eventually I stopped teaching and ...moreMore about Jeanne Betancourt...
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Puukko Knife Holder: Knife Block + Magnetic Strip
The kitchen is often over looked as the hub for all things gadget or tech related when it comes to consumer products. However, it's a bastion for some of the geekiest gadgets in the home. You're probably thinking of blenders, high end toaster ovens, but we're gonna take it a different direction and take a look at a unique knife holder.
This Puukko is the perfect intersection of a knife block and one of those not so pretty metal knife strips. It's a slab of old-growth (300 years) Cypress infused with a magnetic strip. This keeps your blades neatly on display, and is both functional and aesthetically pleasing. They also offer a Redwood version if you're not digging the Cypress.
Each cost $125.
Christen Costa
Grew up back East, got sick of the cold and headed West. Since I was small I have been pushing buttons - both electronic and human. With an insatiable need for tech I thought "why not start a blog focusing on technology, and use my dislikes and likes to post on gadgets."
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1 Comment to Puukko Knife Holder: Knife Block + Magnetic Strip
Why on earth are these knives displayed upside down?


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A Technical Project Manager at Verimatrix is a highly visible, customer-facing team member responsible for managing complex, multi-phase high-profile, and mission-critical customer projects for our customers, partners and resellers. The Technical Project Manager represents10/22/2014 San Diego, CA Save This Job
pportunity Details: Overview: Arise Virtual Solutions is a work-at-home business process outsourcing company that uniquely blends crowdsourcing innovation, virtual technology and operational efficiencies to deliver better results. Recognized as a work-at-home call center10/21/2014 Miramar, FL Save This Job


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Pinky Rideau gave everything she had when she was up on the gazebo stage at Library Park Tuesday afternoon.
Mary Hildebrand lived through one of the worst snowstorms to hit Pennsylvania during the early part of the 20th century.
Eight-year-old Alyssa Rose Elliott was enjoying her first day of the summer break.
YOSEMITE NATIONAL PARK – Yosemite Conservancy, a nonprofit organization benefitting Yosemite National Park and its millions of visitors, was launched last week with commendations by public officials, songs by local school children and cheers of people who love the park.
MOUNTAIN HOUSE - The Mountain House Kite & Multi-Cultural Festival returns Saturday, June 12, to fill the skies with colorful kites and the air with laughter and music.
Merrill Gardens at Manteca will celebrate Support Our Troops Week by hosting a Big Band Swing Concert played by "Tradewinds Dance Band" on Thursday, June 17, at 6 p.m. at the retirement community located at 430 N. Union Road.
Wanted: Blood donors to help Sierra Johnson, the 20-year-old Fresno State sophomore who is fighting acute lymphocytic leukemia complicated by Philadelphia Chromosome.
Every first Friday of the month at 7 p.m., a group of women meet at Crossroads Grace Community Church on Moffat Boulevard.
Manteca's "Magic Bus" is not a salute to the rock-n-roll band The Who that popularized the song with that name.
Megan Germann and Mallory Luck didn't have any experience with Give Every Child a Chance prior to two weeks ago.
Precision Automotive was busy as usual on Saturday. Owner Chris Kohl with a small flashlight in hand was in the shop peering at the undersides of cars perched on hydra-lifts. His wife Shelley was inside the office attending to that part of the business.
Sitting at the kitchen table interviewing the retired master sergeant, it was clear that the former tank platoon leader was someone who had given his all in his devotion to country - serving in both Korea and Vietnam.
Manteca is again avoiding paying triple overtime to police officers as well as shaving thousands off the cost of the aerial fireworks by shifting the community's Independence Day celebration to July 3.
Spanish explorers climbing to the top of Mt. Diablo in the early summer of 1776 thought they had stumbled onto a great inland lake.
The double-crested cormorant is not on any endangered species list.
It is going to cost nearly $150 million for levee upgrades to protect Manteca, Lathrop, Weston Ranch, and parts of rural south Manteca from a 200-year flood.
It's now the $310 million question.
Jim Anderson - a popular home-grown rock singer that pays tribute to Elvis Presley's early years - is performing on the Main Stage of the 30th annual Sunrise Kiwanis Pumpkin Fair this weekend in downtown Manteca.
The Moving Wall - an 80 percent replica of the Vietnam Memorial in Washington, D.C., - is returning to Manteca a little more than 20 years after its first appearance.
Editor's note: This is an abbreviated version of a column about the Manteca High Vietnam Moving Wall ceremonies that former Manteca High student and Congressional Medal of Honor recipient Sammy Davis appeared at that was published in March of 1993.
Good luck getting California's diverse special interest groups to agree on anything.
Educator Shane Smith is on the ballot for the Nov. 4 vote for Ripon City Council election even though he says he has been talked out of running because he is relatively new to the community.
The Home Energy Opportunity (HERO) program is considered as one of the fastest growing energy efficiency financing solution in the country.
You can tell a lot about a city by its garbage.
"Fight Hunger, Spark Change" is the theme of the current online voting contest that could give the San Joaquin and Stanislaus Counties Food Bank in Manteca a $60,000 prize courtesy of Walmart.
Manteca is rallying to help 19-year-old Jose Maltez.


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Carolina Beach Townhome Rental Photos and Description
Townhome, 4 Bedrooms + Convertible bed(s), 4.5 Baths, (Sleeps 10-12)
916-1 Canal Dr. ('A Deck Above') - Carolina Beach, NC.
4 bedrooms and 4.5 bathrooms over 2372 square feet! 3 spacious floors with 2 balconies on each floor. What makes this home 'above' the rest? The Double Deck off the kitchen features unbelievable water views you can appreciate on another level!
Not a stairs person? No problem! There is a private, indoor elevator on each floor. Just a short stroll to beach access. Sleeps 12 comfortably.
First Level: 2 spacious bedrooms, each with their own full bathroom. Bedroom #1 faces the ocean, has twin bunk beds, 2 closets, a TV and its own balcony. Bedroom #2 faces the yacht basin, has a queen bed, 2 closets, a TV and a balcony with small views of the yacht basin. In between the bedrooms is a laundry closet with a full-size, side-by-side washer and dryer with light shelving for laundry supplies.
Second Level: 2 more spacious bedrooms, each with their own full bathroom. Bedroom #3 faces the ocean, has a queen bed, 2 closets, a TV and a balcony. Bedroom #4 faces the yacht basin, has a queen bed, TV, closet, double vanity (2 sinks) in the bathroom, and a great view of the canal from the balcony.
Third Level: Spacious living area! The third level features a living room with a sofa, recliner chairs, TV, balcony with unobstructed views of the yacht basin, 2 kitchen tables that seat 12 comfortably, 1 high chair, and the beautiful kitchen with full-size refrigerator, stove, oven, dishwasher, cabinet space, and breakfast bar with barstools. A half-bathroom is on this floor for added convenience. Relax on the ocean view deck off the kitchen...or kick it up a notch and climb up one more level to a '4th level' view of the ocean!
Wireless internet is included. Small dog considered with additional fee. NO smoking inside the home.
*** Taxes, linens and travel insurance are not included in pricing. Any daily rates that are available will be advertised here as Specials. Daily rates require a 3-NIGHT minimum stay. ***
To book, reply to this ad. This rental is managed by OceanBreeze Properties, LLC. Equal Housing Opportunity.
Visit us on Facebook!
Keywords: Yacht basin, canal views, Ocean View, 3rd Row, town house, beach, surf, sand, relax
- Suitability:
- Minimum Age Limit for Renters
- children welcome
- limited accessibility
- non smoking only
- pets considered


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text: First found this little hole in the wall in Brookline by mistake a few years ago on a hot summer night when their a/c was broken. Despite that, the food was excellent and we have returned almost every time we are in Boston. There is a selection of savory and sweet crepes with the option to build your own. While... More


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Moms and grandmothers know a lot about emergencies
April 4, 2014
Mothers of all ages know about dealing with emergencies. But there are some specific things that moms with young children, or elders with unique needs in the home can think about to deal with their unique situations:
- Have I taken an inventory of my home to see what we have for food and emergency supplies?
- Do I know what my community's emergency plans and resources are?
- Have I made a plan for communicating with my family members if we are not together when an emergency happens?
- Do I have the emergency supplies I need both to stay in my house and if I have to evacuate?
We all know Moms Rule: These ideas will help you captain the family ship through any storm.Sign up to receive our Daily Safety and Preparedness Tips
- November 28, 2014: Be thankful, and be safe
- November 27, 2014: Turkey safety alert! Thaw safely. cook thoroughly, enjoy heartily
- November 26, 2014: Go over the river and through the woods -- safely
- November 25, 2014: Sometimes asking for help is a sign of strength
- November 24, 2014: Look carefully and signal before changing lanes
- November 23, 2014: Slow down and get there faster
- November 22, 2014: Make your holiday gift decisions easy: NOAA Weather Radios
- November 21, 2014: Help your first responders by helping yourself
- November 20, 2014: Sometimes your parents actually are right
- November 19, 2014: When your carbon monoxide alarm goes off, know what to do
- November 18, 2014: Carbon monoxide alarms can save a life
- November 17, 2014: Carbon monoxide safety is important outside your home as well as inside
- November 16, 2014: Rain, rain and more rain ... no matter what the season
- November 15, 2014: It takes all needs to make a plan
- November 14, 2014: Feed your car, avoid a freezing
- November 13, 2014: Listen to all that talk about the weather
- November 12, 2014: Help your pet with his emergency plan
- November 11, 2014: Today is Veterans Day: Keep faith by keeping safe
- November 10, 2014: Floods aren't just for springtime
- November 9, 2014: Your car needs a winter survival kit.
- November 8, 2014: If you're a man, pay attention - if you care about a man in your life, pay attention
- November 7, 2014: Slow down before you slip and slide
- November 6, 2014: Warmth comes in layers
- November 5, 2014: Look out below!
- November 4, 2014: You have a vote. Use it.
- November 3, 2014: How to prevent CO Poisoning during Power Outages
- November 2, 2014: Set your clocks back tonight and think of other ways to save energy
- November 1, 2014: Help a friend in need to clear away debris
- October 31, 2014: Ghosts, Goblins and Witches - OH MY!
- October 30, 2014: Put safety first when water is high


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The president's wariness of whistleblower protections could discourage feds from reporting wrongdoing, lawmakers fear. (Stock Image)
Lawmakers from both parties are urging President Barack Obama to institute the enhanced whistleblower protections in the new defense authorization bill, despite his criticism of the provisions.
"We are concerned your statement that accompanied the signing of the [fiscal 2013 National Defense Authorization Act] into law may be perceived as undermining congressional intent and discouraging individuals from helping to protect taxpayer dollars," Sens. Claire McCaskill (D-Mo.) and Charles Grassley (R-Iowa) and Reps. Darrell Issa (R-Calif.) and Elijah Cummings (D-Md.) wrote in a Jan. 17 lettter. "Furthermore, your statement could be perceived as potentially eroding protections for federal workers and discouraging them from helping expose improper behavior."
The four lawmakers noted that, since they oversee the executive branch, both public-sector and private-sector employees have an obligation to bring information to Congress. They encouraged Obama to have his administration enforce the defense bill's provisions to "show its dedication to transparency and accountability."
McCaskill has been a senior member of the committees on Armed Services and Homeland Security and Governmental Affairs. Grassley has been a senior Finance Committee member. Issa and Cummings are the chairman and ranking member, respectively, of the Oversight and Government Reform Committee.
Outside experts have suggested Obama's statement creates doubt about how agencies will handle whistleblower protections for contractors.
"We are really pleased to see these members of Congress standing up for whistleblowers and their constitutional duties of oversight," said Angela Canterbury, director for public policy at the Project on Government Oversight. "Congress has far too often ceded power to the presidency. But these lawmakers are obviously not rolling over."
Canterbury added that POGO would be doing its part to support whistleblowers as well.
"We will be keeping a close eye on how the new whistleblower protections are put into practice," she said. Obama's comments "already caused confusion, and very likely will create a chilling effect on disclosures of waste, fraud, and abuse. Congress needs to make it clear that the president cannot limit their right to know."
The president signed the defense bill into law on Jan. 2, but also issued an accompanying signing statement that said the provisions allowing contractors to expose government waste and gross mismanagement directly to Congress "could be interpreted in a manner that would interfere with my authority to manage and direct executive branch officials."
Obama warned lawmakers that his administration will closely watch contractors' interactions with Congress. "I will interpret those sections consistent with my authority to direct the heads of executive departments to supervise, control, and correct employees' communications with the Congress in cases where such communications would be unlawful or would reveal information that is properly privileged or otherwise confidential," he wrote.
The law protects contractor employees who disclose information that they reasonably believe to be evidence of gross mismanagement, abuse of authority, or violations of laws, including regulations regarding contract negotiations and awards. The bill permanently covers all employees of defense contractors and subcontractors who bring forth the evidence, and states that the new rights cannot be waived under any agreement or policy.
The bill also extends protections to whistleblowers who are harassed or fired by a contractor at the government's direction. And it establishes a four-year pilot program enhancing whistleblower protections applicable to all civilian federal agency contractors. Those protections then could become permanent.
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Steve Kelman considers the costs of corruption in Mexico, China, and most developing countries -- and argues that Americans should keep their own government troubles in perspective.
Agency leaders must proactively invest time, energy and resources to shape the future rather than reactively wait for change to happen.
Meet 24 men and women who are driving key changes in federal IT -- and shaping up as the community's likely leaders of tomorrow.
GSA's administrator talks with FCW about short-term hiring, long-term planning and Robert Frost.
Without a future vision and an appetite for risk, reforms lead down a rabbit hole. There is a better way.
VA's top tech official says he is balancing risks while trying to keep the department's online services open for business.
After five years on the job, the founding director of the Office of Government Information Services believes that a deeper understanding and acceptance of FOIA is seeping into the federal government.
The September attack, made public Nov. 10, potentially puts customer and employee personal information at risk, including addresses, Social Security numbers and emails.
The General Services Administration's Matthew Goodrich predicts more agency-driven authorizations and previews a new two-year road map.
I recently filed a whistleblower complaint with DOD-IG as a contractor employee on federal contract illegalities. DOD-IG closed the case without conducting a proper investigation. When questioned as to the reason, DOD-IG gave conflicting explanations that were not consistent with the statute language. If they can operate with such arrogance now, imagine how they will be in the future.
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Jon Hevelone's blog
HypocritesSubmitted by Jon Hevelone on Sat, 08/30/2014 - 00:00
Hypocrites. The church is full of them.
Haven't you heard that complaint from people in your life? Haven't you said it yourself? Research from the Barna Group shows that this is the most common complaint about churches made by young adults.
Well, I categorically deny that it is true, at least as far as First Baptist Arlington is concerned. Hypocrites in our church? Absolutely. But as you can obviously see any Sunday morning, we are not "full" of them. There is plenty of room for many more. I would guess our sanctuary could easily hold another two hundred or so without major crowding. Then, we could go to two services.
Christian churches are filled with folks who say one thing and then do something else. We sing "They'll know we are Christians by our love, by our love," and then go out and walk all over people who cross us or just happen to be in our way. We hold to the high moral standards that happen to be our own personal "hot button" issues, but are blind to the ways we play fast and loose with our list of "acceptable" sins.
Somebody once looked at a group of people an awfully lot like us — people who did not practice what they preach — and said: "Woe to you…you hypocrites! You shut the door of the kingdom of heaven in people's faces. You yourselves do not enter, nor will you let those enter who are trying to." (Matthew 23:13)
This is a problem: when Christian people do not live up to the high standards of their faith, others notice our behavior. The way we treat the waitress, the tone we use with our children, the looks we give to others we pass on the sidewalk, the attitudes and behaviors that mark our personality are noticed. When what others see about us does not match what we say the label comes out: Hypocrite!
There is an easy, commonly used way to solve the whole problem, and get rid of the gap that leads to the dreaded label. Just lower our standards! If there are no high expectations, then there is no lofty height from which to fall. If I personally have no vision of truth, morality, or purposefulness in life, then I am free to live as it benefits me.
Shifting standards to whatever level is convenient or desirable is not possible for a Christian. There has been a high bar set, and if I am intent on practicing my faith, my goal is to shift my life upward to meet those standards. I have been called to follow Jesus Christ. Period. When I fall short, which I constantly do, there is forgiveness. When I get up and try again God does help. When I live Christianly, there is hope. And every time I fail to meet the high standards yet still keep on by faith, it is my prayer that those on the outside looking at me will see me truly for who I am — a hypocrite loved and being redeemed by Jesus.
Heaven's ChurchSubmitted by Jon Hevelone on Thu, 05/29/2014 - 13:24
I did something really embarrassing in our church service Sunday. As I preached a message I repeated the words of an old, old (very Baptist!) hymn, When We All Get to Heaven.
Sing the wondrous love of Jesus;
sing his mercy and his grace.
In the mansions bright and blessed
he'll prepare for us a place.
And then the chorus comes ringing in:
When we all get to heaven,
what a day of rejoicing that will be!
When we all see Jesus,
we'll sing and shout the victory!
I was surprised that hardly anyone in our congregation had heard of it, and so at the end of my sermon I walked to the piano and started playing. Carried away, I began singing the words. If you have ever heard my singing you know what it sounded like. Luckily, nobody walked out.
Which brings me to the Bible's picture of worship in heaven, with a massive white robed choir of redeemed people singing praises to God. With a choir that size gathered from the four corners of the earth singing to God himself, no less, they had to be good. It's pretty obvious that they've been to choir practice. Lots of choir practice, if any of them sounded like me.
Likewise, as we look ahead to the time when we will be in Heaven's Church we better pay close attention to the church family we are in here on earth. Being part of a fellowship of believers, a church, is absolutely vital if we are going to grow in our faith.
We are so much a part of an individualistic culture in America. We think we can worship God sufficiently while hiking the Appalachian trail or out on the golf course or beach combing or sitting home with our telly-vangelist, but we can't. We need each other. We need to be connected with others in Christ's body so we don't stagnate, but rather develop maturity ourselves and help others along in their own life journeys.
Jesus never said that where one person is walking down Mass Ave on an iPhone listening to Red Hot Chili Peppers or Death Cab for Cutie that he was there with them. No, he said "For where two or three are gathered in my name, I am there among them." (Mt 18:20) This isn't my take. This is what Jesus said. Deal with it.
In Alice in Wonderland Lewis Carroll had Alice ask, "Cheshire-Puss, would you please tell me, which way I ought to go from here?" The cat answers, "That depends a good deal on where you want to get to." If you want to get to Heaven's Church -- or heaven itself, for that matter -- you better get to know the One who is The Way. He has prepared a place for you in heaven, and also one right here on earth for you. In this earthly place you can practice your singing skills in choir rehearsal as well as all the other skills that go into living Christianly. You don't want to be embarrassed when you do show up at Heaven's Church singing and shouting the victory!
BasketballSubmitted by Jon Hevelone on Mon, 05/05/2014 - 13:37
With the NBA playoffs still occasionally making headlines despite the media circus that swirls around the Los Angeles Clippers and their bigot billionaire boss, Donald Sterling, I am reminded that preaching is a lot like the game of basketball. There are times when you are hot, and there other times when you just can't hit the basket.
I've had my fair share of both experiences. (Preaching, not shooting hoops.) Sometimes I feel as if I can turn my back to the basket, flip the ball over my head, and know it will slip in with nothing but net. Then there are times I give it my best shot and can't even hit the backboard. The funny thing is that those times when I'm on are often the times when I let the Holy Spirit do the work, and the times when I'm off correlate with my strange idea that I can do it better myself.
So how do you preach? With power, with conviction?
"But Pastor Jon, I don't preach at all."
Oh yes, you do. Every one of us preaches -- by our lives. If we are to have a viable church, an effective Christian influence in Arlington and the other communities in which we live and work, then we need the Spirit's presence in our lives. If somehow we expect to help meet the deep needs in people's lives, only the power of God is sufficient.
The only thing that will make a church relevant today, the only thing that will give you credibility and make you useful in serving the Lord will be God's presence in your life. When we live Christianly -- being open to God giving us new depth and integrity in our faith, we will find that who we are will "preach" loudly in a society that craves authenticity and soul.
Christian character in a world of racial bigots, greed, and frivolous sexuality is an unanswerable and powerful kind of statement. It is one that we as followers of Jesus Christ must make in our daily life. Please notice I am not talking about an increased religiosity or "churchiness" -- a superficial coating of sweet evangelical piety or a display of phony churchmanship. I am talking about you and I being in contact with God in such a way that somehow, despite all of our imperfections and weaknesses and mistakes the presence of Christ can still be seen in our lives.
Is there evidence of this in our lives today? In my life? In yours? If so, it will preach. And meanwhile, go Doc Rivers! Go LA Clippers! And go First Baptist family! Preach it!
HabitsSubmitted by Jon Hevelone on Sat, 01/04/2014 - 23:02
We are people of habit. So much of what we do is done on "auto-pilot," allowing us to get the routine things done while our mind is focused on other things. Sometimes habits are rather strange, or even unproductive. I must frequently participate in that barbaric ritual of wearing a tie. I can not tell you how many times I have tied a tie. I have the procedure down pat. Yet to this this day I can not tie one unless I am looking in a mirror. No mirror, no knot.
Someone said that a habit is just a behavioral groove we get into. Unfortunately, sometimes we dig the groove so deep that it becomes a rut, and we are stuck. This gets pretty bad when the habit or groove we find ourselves stuck in is destructive. You do know about these kinds of habits, don't you? Feasting on too much junk food, slacking off, or poisoning the air with gossip or inappropriate responses are all habits that can reap unhappy consequences.
If a habit is a grooved behavior pattern, then perhaps we can also groove our spiritual growth, creating patterns that are more more Christlike. These new habits can lead to a far healthier spiritual life than we've settled for in the past. In fact, Paul advocates training ourselves in godliness, or as he puts it:
Stay clear of silly stories that get dressed up as religion. Exercise daily in God—
no spiritual flabbiness, please! Workouts in the gymnasium are useful, but a
disciplined life in God is far more so, making you fit both today and forever.
(1 Timothy 4:7-8)
Let me toss out two suggestions for beginning your spiritual workout. First, get in the habit of starting your morning with God. Waking up aware that God has given you yet another day to live unleashes enormous positive possibilities. Instead of hitting the snooze on that blasted alarm clock and pulling the covers up over your head, consider yourself blessed that you have a precious day given you by Someone who totally loves you, has your best interests at heart, and has offered to help you not only get through the day, but become a far finer person than you ever could on your own. Let Psalms 118:24 be your wake up call: "This is the day the Lord has made. I will rejoice and be glad in it."
Secondly, make it your habit to identify a specific ministry to do for God for the day. What will you do that honors the Lord, helps someone's life to be a little better, and builds up God's Kingdom? Paul's vision for followers of Jesus is for us to "excel in gifts that build up the church" ( 1 Corinthians 14:12). What gift will you give today? Will it be a smile? A friendly word of encouragement? A chunk of your time? Some sweat and muscle power? Prayer? How can you let your light shine so people will praise God because of you? Get in the habit of using some time during each day ministering. It's a behavioral groove that will keep you in top spiritual shape for life.