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|Aug 22, 2000
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|Mar 25, 1998
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|Mar 26, 1997
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|Jan Henrik Ardenkjaer-Larsen
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|Nycomed Imaging As
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|Patent Citations (5), Non-Patent Citations (5), Referenced by (22), Classifications (8), Legal Events (4)
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This invention relates to a method of dynamic nuclear polarisation enhanced magnetic resonance imaging.
Magnetic resonance imaging (MRI) is a diagnostic technique that has become particularly attractive to physicians as it is non-invasive and does not involve exposing the patient under study to potentially harmful radiation such as X-rays.
The thermal equilibrium magnetisation of a sample of nuclear spin I in a magnetic field B0 is given by the Boltzmann distribution: ##EQU1## where γI is the magnetogyric factor of the nucleus, NS is the number of spins per unit volume and T is the temperature of the sample. The population difference between nuclear levels at room temperature is usually extremely small due to the low Zeeman energy of the nucleus and therefore according to the Curie law ##EQU2## At typical fields of 1-1.5T the relative population differences are ≈10-5 and the MR signals obtained are of low amplitude.
Electron spin resonance enhanced MRI (referred to in earlier publications as ESREMRI, OMRI or PEDRI) is a method of dynamic nuclear polarisation enhanced MRI in which enhancement of the magnetic resonance signals from which images may be generated is achieved by virtue of the dynamic nuclear polarization (the Overhauser effect) that occurs on VHF stimulation of an ESR transition in a magnetic material in the subject under study. Magnetic resonance signal enhancement may be by a factor of a hundred or more thus allowing enhanced images to be generated rapidly and with relatively low primary magnetic fields.
In the basic in vivo OMRI technique, the imaging sequence involves initially irradiating a subject placed in a uniform magnetic field (the primary magnetic field, B.) with radiation, usually VHF radiation, of a frequency selected to excite a narrow linewidth ESR transition in an OMRI contrast agent which is in (eg. oxygen or melanin), or has been administered to (eg. a free radical), the subject. Dynamic nuclear polarization results in an increase in the population difference between the excited and ground nuclear spin states of nuclei which are responsible for the magnetic resonance signals. Since MR signal intensity is proportional to this population difference, the subsequent stages of each imaging sequence, performed essentially as in conventional MRI techniques, result in larger amplitude MR signals being detected.
The basic equation of dynamic nuclear polarisation is given by: ##EQU3## where γS is the electron magnetogyric factor and SAT is the saturation degree of the electron spin resonance (which approaches unity as the excitation field is increased). The ratio between the magnetogyric factor of the electron and the proton is 658. f is the leakage factor and k is the coupling factor where: ##EQU4## where T10 is the relaxation time of the pure solvent, r1 is the relaxivity and c is the concentration of the free radical. J(ω,τ) are spectral densities that depend on the relative motion of the two spins I and S. The correlation time, ##EQU5## where d is the minimal distance of approach and DI, DS are the absolute translational diffusion constants of the two spins.
OMRI techniques have been described by several authors, notably Leunbach, Lurie, Ettinger, Grucker, Ehnholm and Sepponen, for example in EP-A-296833, EP-A-361551, WO-A-90/13047, J. Mag. Reson. 76:366-370(1988), EP-A-302742, SMRM 9:619(1990), SMRM 6:24(1987), SMRM 7:1094(1988), SMRM 8:329(1989), U.S. Pat. No. 4,719,425, SMRM 8:816(1989), Mag. Reson. Med. 14:140-147(1990), SMRM 9:617(1990), SMRM 9:612(1990), SMRM 9:121(1990), GB-A-2227095, DE-A-4042212 and GB-A-2220269.
One particular method of dynamic nuclear polarisation enhanced MRI relies on ex vivo dynamic nuclear polarisation of selected nuclei of an MR imaging agent by an OMRI contrast agent (eg. a free radical), the latter conveniently being disposed of prior to administration of the polarised MR imaging agent into the subject. This method is described in UK Patent Application No. 9614139.5 filed on Jul. 5, 1996 in the name of Nycomed Imaging AS. The present invention is based on the finding that dynamic nuclear polarisation can be formed at higher field strengths by increasing the temperature of the sample. Heating the MR imaging agent prior to or during ex vivo polarisation increases the T1 relaxation time.
Thus viewed from one aspect the present invention provides a method of magnetic resonance investigation of a sample, preferably of a human or non-human animal body (eg. a mammalian, reptilian or avian body) comprising ex vivo polarisation eg. dynamic nuclear polarisation of an MR imaging agent characterised in that the MR imaging agent, preferably together with an OMRI contrast agent, is heated during or prior to polarisation.
Viewed from a further aspect the present invention provides a method of magnetic resonance investigation of an animate subject comprising ex vivo polarisation of an MR imaging agent, characterised in that the MR imaging agent, preferably together with an OMRI contrast agent, is heated during polarisation or is at elevated temperature at the time of polarisation.
In one particular embodiment, the method comprises:
(i) placing a composition comprising an OMRI contrast agent and an MR imaging agent in a uniform magnetic field (eg. the primary magnetic field B0);
(ii) heating said composition;
(iii) exposing said composition to a first radiation of a frequency selected to excite electron spin transitions in said OMRI contrast agent;
(iv) separating the whole, substantially the whole, or a portion of said OMRI contrast agent from said MR imaging agent;
(v) cooling said MR imaging agent;
(vi) administering said MR imaging agent to said sample;
(vii) exposing said sample to a second radiation of a frequency selected to excite nuclear spin transitions in said MR imaging nuclei;
(viii) detecting magnetic resonance signals from said sample; and
(ix) optionally, generating an image or dynamic flow data from said detected signals.
Conveniently, step (iii) may serve to provide the desired increase in temperature of the composition making step (ii) optional.
Thus in one embodiment the invention involves the sequential steps of heating an MR imaging agent, ex vivo dynamic nuclear polarisation of MR imaging nuclei, administration of cooled, polarised MR imaging nuclei in the absence of a portion of, preferably substantially the whole of, the OMRI contrast agent, and conventional in vivo MR signal generation and measurement. The MR signals obtained in this way may be conveniently converted into 2- or 3-dimensional image data or flow data. By MR imaging agent is meant an agent containing nuclei (MR imaging nuclei) capable of emitting magnetic resonance signals. Generally such nuclei will be protons, preferably water protons; however, other non-zero nuclear spin nuclei may be used (eg. F or Li nuclei) and in this event the signals from which the image is generated will be substantially only from the MR imaging agent itself.
In a further embodiment, ex vivo polarisation may be achieved in the absence of an OMRI contrast agent by imposing a field higher than B0. Thus the method involves the sequential steps of heating an MR imaging agent such as a physiologically tolerable aqueous fluid, ex vivo polarisation using for example a strong superconducting magnet with a field of 5T or more, preferably a field in the range 8-15T, cooling, administration and conventional in vivo MR signal generation.
The method according to the invention may be conveniently carried out by using a first magnet for providing the polarising magnetic field and a second magnet for providing the primary magnetic field for MR imaging. An OMRI apparatus suitable for use in the present invention comprises a first magnet providing a magnetic field for dynamic nuclear polarisation and a second magnet providing the primary magnetic field for MR imaging of a subject (eg. an animate subject). FIG. 1 of the accompanying drawings is a schematic representation of one embodiment of the apparatus according to the invention. Therein a polarising magnet (which may be freestanding or the polarising and imaging magnets may be the same) (1) optionally together with a filter surrounds an EPR resonator (2) which provides the dynamic nuclear polarisation. A container (3) comprising a pump is provided for carrying the contrast composition which is delivered to a subject (4) by a delivery line (5). The container is also provided with means for heating the contrast composition. For the purposes of rapidly cooling the polarised MR imaging agent to physiological temperatures, a cold trap (9) is provided together with a container (8) and delivery line (7) for delivering for example cold saline solution (eg. Ringers Solution at -15� C.) or other physiologically acceptable media. The subject is situated within a conventional MR scanner (6).
Any conventional means may be used for the purposes of the heating step in the method according to the invention eg. infra-red or microwave means in conjunction with a conventional temperature controller. The optimum temperature will of course be dependent on the nature of the MR imaging agent and OMRI contrast agent and may be readily empirically determined. Preferably the temperature is about 40� C. or more, especially about 45� C. or more. Where the MR imaging agent is water, the optimum temperature will typically be in the range 45-95� C., preferably 60-95�.
The irradiation of the magnetic resonance of the OMRI agent is achieved by a resonator or antenna structure suitable for providing the appropriate resonant magnetic field. This is mainly perpendicular to the static field and of sufficient magnitude to approach saturation of the resonance in the whole sample volume, or at least the part of the sample which is injected into the subject. The irradiation of large volumes, preferably 10-100 ml, more preferably 50-100 ml or more, at high frequencies is a technical challenge. The appropriate construction may be a modification of resonators or antennas known in the field of magnetic resonance, for example cavity resonators, dielectric resonators, loop gaps and microstrip structures.
A dielectric resonator may be used in the dynamic nuclear polarisation process, typically to provide a field arrangement in which the magnetic field lines are shaped like a straw in a sheaf of corn with an electric field forming circles like the thread binding the sheaf. A field arrangement of this type may be formed by one of several rings or tubes of a material with a high dielectric constant and low loss. The man skilled in the art will appreciate that such a tube will exhibit different electromagnetic resonant modes. One of the dominant modes has the desired characteristic of electric field circulating around the tube axis within the wall and being zero at the axis and everywhere perpendicular to it. The magnetic field on the other hand is concentrated around the tube axis and mainly directed along it. The composition to be polarised is conveniently placed inside the resonator which is itself placed inside a metal box with a clearance typically of the order of the size of the resonator, and is excited to the desired resonance with a coupling loop or the like. The metal box ensures that the electromagnetic energy does not leak away by radiation. FIG. 2 of the accompanying drawings shows a dielectric resonator (1) (with an axis of rotational symmetry (2)) within a metal box (3).
An alternative embodiment to the dielectric resonator is a resonant cavity of which several are known to those skilled in the art. One simple and efficient resonant cavity is a metal box, such as a cylindrical metal box. A suitable mode is the one known as TM1,1,0 which produces a perpendicular magnetic field on the axis of the cavity. It is possible to excite two such modes in the same cavity at the same frequency producing fields which are mutually perpendicular. By arranging them to have a 90� phase difference a rotating field can be produced which is especially efficient for implementing dynamic polarisation with a minimum of dissipation in the sample. Modes with similar field distributions for different shapes of cavities e.g. rectangular cavities are familiar to those skilled in the art.
The composition may be dispersed into a plurality of compartments during the dynamic nuclear polarisation step. Thus the composition might be typically divided into parallel channels provided, for example, by parallel separating plates, discs or tubes, typically open-ended tubes. The electric losses (eddy currents) in the composition caused by the magnetic field are decreased by dividing the composition into smaller volumes using electrically isolating barriers, preferably situated perpendicular to the field. If the composition is in a cylindrical vessel surrounded by a dielectric resonator as described hereinbefore, the isolating barriers would be planes passing radially from the vessel axis to its wall. A simpler and more practical arrangement is to polarise the composition in a container which contains a plurality of thin-walled tubes of an isolating material such as quartz, glass or plastic. This has the advantage of reducing the electric losses in the composition which allows a larger volume of composition to be polarised for the same applied electromagnetic power. The walls, the inner, outer or both of the tubes may similarly serve as the substrate onto which the OMRI contrast agent is bound so that pressure applied to one end of the container by for example a plunger or pressure applicator may force the polarized, substantially OMRI contrast agent free, fluid MR imaging agent from the container, into a delivery line leading to the subject (patient) undergoing MR examination.
In a further embodiment, any known OMRI contrast agent capable of effecting a diagnostically effective contrast enhancement in the sample to which the MR imaging agent is administered may be used as an OMRI contrast agent in the present invention, provided that it is stable for a sufficient period of time at the elevated temperature at which it is desired to carry out polarisation. Where the OMRI contrast agent is a paramagnetic free radical, the radical may be conveniently prepared in situ from a stable radical precursor by a conventional physical or chemical radical generation step shortly before the method according to the invention is effected. This is particularly advantageous where the radical has a short half-life. In these cases, the radical will normally be non-reusable and may conveniently be discarded once the separation step of the method according to the invention has been completed.
Preferred OMRI contrast agents for use in the method according to the invention are those which can be conveniently and rapidly separated from the polarised MR imaging agent using known techniques as discussed below.
Preferably of course a chosen polarising agent will exhibit a long half-life (preferably at least one hour), long relaxation times (T1e and T2e), high relaxivity and a small number of ESR transition lines. Thus the paramagnetic oxygen-based, sulphur-based or carbon-based organic free radicals or magnetic particles referred to in WO-A-88/10419, WO-A-90/00904, WO-A-91/12024, WO-A-93/02711 or WO-A-96/39367 would be suitable OMRI contrast agents for the present invention. A particularly preferred characteristic of a chosen OMRI contrast agent is that it exhibits low inherent ESR linewidths, preferably less than 500 mG, particularly preferably less than 400 mG, especially preferably less than 150 mG. Generally speaking, organic free radicals such as triarylmethyl and nitroxide radicals provide the most likely source of such desirably low linewidths eg. those described in WO-A-88/10419, WO-A-90/00904, WO-A-91/12024, WO-A-93/02711 or WO-A-96/39367.
Paramagnetic radical particles are also preferred for use in the present invention. Examples include "chars" particles conveniently dispersed in water and lithium phthalocyanine radical particles (see EP-A-467747). The definition of "char" as used herein refers to burned carbohydrates which are burnt at a temperature which is significantly lower than that used to produced graphite, typically 500� C.-800� C.
However, OMRI contrast agents useful in the present method are not limited to paramagnetic organic free radicals. Particles exhibiting the magnetic properties of superparamagnetism, ferromagnetism or ferrimagnetism may also be useful OMRI contrast agents, as may be other particles having associated free electrons. Superparamagnetic nanoparticles (eg. iron or iron oxide nanoparticles) may be particularly useful. Magnetic particles have the advantages over organic free radicals of high stability and a strong electronic/nuclear spin coupling (ie. high relaxivity) leading to greater Overhauser enhancement factors.
For ease of separation of the OMRI contrast agent and the MR imaging agent, it is particularly preferred that the combination of the two be a heterogeneous system, eg. a two phase liquid, a solid in liquid suspension or a relatively high surface area solid substrate within a liquid, eg. a solid in the form of beads fibres or sheets disposed within a liquid phase MR imaging agent. In all cases, the diffusion distance between the MR imaging agent and OMRI contrast agent must be small enough to achieve an effective Overhauser enhancement. Certain OMRI contrast agents are inherently particulate in nature, eg. the paramagnetic particles and superparamagnetic agents referred to above, others may be immobilized on, absorbed in or coupled to a solid substrate or support (eg. an organic polymer or inorganic matrix such as a zeolite) by conventional means. Strong covalent binding between OMRI contrast agent and solid substrate or support will, in general, limit the effectiveness of the agent in achieving the desired Overhauser effect and so it is preferred that the binding, if any, between the OMRI contrast agent and the solid support or substrate is weak so that the OMRI contrast agent is still capable of free rotation.
For in vivo imaging, the MR imaging agent used in the present method should have nuclei (eg. protons) capable of emitting magnetic resonance signals and should of course be physiologically tolerable or be provided in a physiologically tolerable form. Besides protons, other physiologically tolerable MR imaging nuclei may of course be used, eg, 19 F, 13 C, 31 P and sodium. Preferred MR imaging agents according to the invention exhibit the properties of inter alia high stability to oxygen, to pH (eg. in the pH range 5-9), to physiological temperatures and are stable in body fluids. They are of course non-toxic and preferably are rapidly excreted.
Conveniently, the MR imaging agent once polarised will remain so for a period sufficiently long to allow the imaging procedure to be comfortably carried out. Preferably, significant polarisation will be retained for at least 10s, more preferably at least 100s. In one embodiment of the method of the invention, the polarised MR imaging agent may be stored in frozen form. At low temperatures the polarisation is retained longer and thus the polarised MR imaging agent may be conveniently stored eg. in liquid nitrogen. Prior to use, it may be rapidly warmed to physiological temperatures using conventional techniques such as infrared or microwave radiation.
Particularly preferred MR imaging agents are physiologically tolerable aqueous solutions (eg. saline) in which protons are the imaging nuclei of interest. However water itself is especially preferred and has the advantage of being physiologically tolerable and may be administered to the subject free from carriers, excipients or formulation aids. With water as the MR imaging agent, the OMRI contrast agent may be chosen to be water soluble (eg. typically the water soluble free radicals described in WO-A-93/02711), or capable of being dispersed in water or suspended in water to produce the desired composition for use in the method according to the invention. The composition may be conveniently stored in this "ready to use" form prior to use.
It will be appreciated that a heated, polarised MR imaging agent must be rapidly quenched to physiological temperatures prior to administration. Thus means for imposing any elevated pressure and temperature on the mixture should be removed at the earliest possible opportunity. Further rapid cooling is possible by adding, for example, cold saturated salt solutions (eg. Ringers Solution at -15� C.) or other cooling agents which conveniently serve to provide a medium in which the MR imaging agent may be administered. Yet further cooling is possible by, for example, contacting the MR imaging agent with a cold surface (eg. a cold trap) prior to administration. Administration should occur in a fraction of the time T1 of the MR imaging agent and should typically be within 3s of the temperature drop. It will be appreciated that in this sense the increased relaxation time T1 provided by the invention is an important improvement in the ex vivo method.
Viewed from a further aspect the present invention provides a physiologically tolerable MR imaging agent comprising water at a temperature of 45� C. or more, preferably in the range 45-95� C., and having an effective nuclear polarisation of 10T or more, preferably 30T or more, especially 50T or more.
Viewed from a yet further aspect the present invention provides the use of a physiologically tolerable aqueous solution (eg. a saturated saline solution such as Ringer's Solution) as a cooling agent for the preparation of a MR contrast medium. Preferably, the MR contrast medium comprises polarised water.
Viewed from a yet still further aspect the present invention provides a method of generating an image of an animate subject comprising ex vivo polarisation of an MR imaging agent, characterised in that the MR imaging agent, preferably together with an OMRI contrast agent, is heated during polarisation or is at elevated temperature at the time of polarisation, and wherein an image of at least part of said subject is generated.
Viewed from a yet still further aspect the present invention provides the use of an MR imaging agent as hereinbefore described for the preparation of a contrast medium for use in methods of diagnosis involving MR investigation of an animate subject.
The method according to the invention has the benefit of being able to provide significant spatial weighting to a generated image. In effect, the administration of a polarised MR imaging agent to a selected region of a sample (eg. by injection) means that the contrast effect is, in general, localised to that region. This of course depends on the extent of biodistribution over the period in which the MR imaging agent remains significantly polarised. In general, specific body volumes (i.e. regions of interest) may be defined with improved signal to noise properties of the resulting images in these volumes.
In one embodiment, a "native image" of the sample (e.g. body) (ie. one obtained prior to administration of the MR imaging agent or one obtained for the administered MR imaging agent without prior Overhauser enhancement as in a conventional MR experiment) may be generated to provide structural (eg. anatomical) information upon which the image obtained in the method according to the invention may be superimposed. This is a particularly useful aspect of the present method given that the polarisation of the MR imaging agent may only last for a short period and so biodistribution within the timescale of the measurement may be limited.
Given that the method of the invention should be carried out within the time that the MR imaging agent remains significantly polarised, once separation has been achieved it is desirable for administration of the MR imaging agent to be effected rapidly and for the MR measurement to follow shortly thereafter. This means that the sample (eg. body or organ) should be available close to the area in which the polarisation has been carried out. The preferred administration route for the MR imaging agent is by injection (eg. bolus injection) or where the lungs are to be imaged by spray, eg. aerosol spray.
The separation step of the method of the invention is intended to remove substantially the whole of the OMRI contrast agent from the composition (or at least to reduce it to physiologically tolerable levels) as rapidly as possible. Many physical and chemical separation or extraction techniques are known in the art and may be employed to effect rapid and efficient separation of the OMRI contrast agent and MR imaging agent. Clearly the more preferred separation techniques are those which can be effected rapidly and particularly those which allow separation in less than one second. In this respect, magnetic particles (eg. superparamagnetic particles) may be advantageously used as the OMRI contrast agent as it will be possible to make use of the inherent magnetic properties of the particles to achieve rapid separation by known techniques. Similarly, where the OMRI contrast agent is a solid bound to a magnetic bead, it may be conveniently separated from the liquid by an appropriately applied magnetic field.
Where the combination of an OMRI contrast agent and MR imaging is a heterogeneous system, it will be possible to use the different physical properties of the phases to carry out separation by conventional techniques. For example, where one phase is aqueous and the other non-aqueous (solid or liquid) it may be possible to simply decant one phase from the other. Alternatively, where the OMRI contrast agent is a solid or solid substrate (eg. a bead) suspended in a liquid MR imaging agent the solid may be separated from the liquid by conventional means eg. filtration, gravimetric, chromatographic or centrifugal means. The OMRI agents in solid form may be lyophilised.
It is also envisaged that the OMRI contrast agents may comprise lipophilic moieties and so be separated from the MR imaging agent by passage over or through a fixed lipophilic medium or the OMRI contrast agent may be chemically bound to a lipophilic solid bead.
One separation technique makes use of a cation exchange polymer and a cationic OMRI contrast agent, eg. a trityl carrying pendent carboxylate groups. Alternatively, acidifying the solution to around pH 4 may cause the OMRI contrast agent to precipitate out. Separation may then be carried out for example by filtration followed by neutralisation. An alternative technique involves adding ions which causes precipitation of ionic OMRI agents which may then be filtered off.
Certain OMRI contrast agents, such as the trityl agents, may have an affinity for proteins. Thus, after polarisation, a composition containing an OMRI contrast agent with a protein affinity may be passed through or over a protein in a form which exposes a large surface area to the agent eg. in particulate or surface bound form. In this way, binding of the OMRI contrast agent to the protein enables it to be removed from the composition.
The OMRI contrast agent will always have a molecular weight larger than that of water and therefore, in general, normal filtering techniques can be used for separating molecules with buffered molecules, ie. hollow fibres.
The MR imaging agents may be conveniently formulated with conventional pharmaceutical or veterinary carriers or excipients. MR imaging agent formulations manufactured or used according to this invention may contain, besides the MR imaging agent, formulation aids such as are conventional for therapeutic and diagnostic compositions in human or veterinary medicine. Thus the formulation may for example include stabilizers, antioxidants, osmolality adjusting agents, solubilizing agents, emulsifiers, viscosity enhancers, buffers, etc. Preferably none of such formulation aids will be paramagnetic, superparamagnetic, ferromagnetic or ferrimagnetic. The formulation may be in forms suitable for parenteral (eg. intravenous or intraarterial) or enteral (eg. oral or rectal) application, for example for application directly into body cavities having external voidance ducts (such as the lungs, the gastrointestinal tract, the bladder and the uterus), or for injection or infusion into the cardiovascular system. However solutions, suspensions and dispersions in physiological tolerable carriers eg. water will generally be preferred.
For use in in vivo imaging, the formulation, which preferably will be substantially isotonic, may conveniently be administered at a concentration sufficient to yield a 1 micromolar to 10 mM concentration of the MR imaging agent (or even higher where the MR imaging agent is water) agent is in the imaging zone; however the precise concentration and dosage will of course depend upon a range of factors such as toxicity, the organ targeting ability of the MR imaging agent, and the administration route. The optimum concentration for the MR imaging agent represents a balance between various factors. In general, optimum concentrations would in most cases lie in the range 0.1M to 10M (or even higher where the MR imaging agent is water), especially 0.2 to 8M, more especially 0.5 to 5M. Formulations for intravenous or intraarterial administration would preferably contain the MR imaging agent in concentrations of 0.1 to 10M (or when the MR imaging agent is water up to 56M), especially 0.5 to 5M. For bolus injection the concentration may conveniently be 0.1M to 10M (or up to 56M when the MR imaging agent is water), preferably 0.2M to 8M, more preferably 0.5M to 5M.
Parenterally administrable forms should of course be sterile and free from physiologically unacceptable agents, and should have low osmolality to minimize irritation or other adverse effects upon administration and thus the formulation should preferably be isotonic or slightly hypertonic. Suitable vehicles include aqueous vehicles customarily used for administering parenteral solutions such as Sodium Chloride solution, Ringer's solution, Dextrose solution, Dextrose and Sodium Chloride solution, Lactated Ringer's solution and other solutions such as are described in Remington's Pharmaceutical Sciences, 15th ed., Easton: Mack Publishing Co., pp. 1405-1412 and 1461-1487 (1975) and The National Formulary XIV, 14th ed. Washington: American Pharmaceutical Association (1975). As has been previously described, cold saturated salt solutions may serve to cool the MR imaging agent prior to administration and are therefore preferred vehicles in the parenteral solutions, typically at a concentration of about 0.15M. The compositions can contain preservatives, antimicrobial agents, buffers and antioxidants conventionally used for parenteral solutions, excipients and other additives which are compatible with the MR imaging agents and which will not interfere with the manufacture, storage or use of the products.
Where the MR imaging agent is to be injected, it may be convenient to inject simultaneously at a series of administration sites such that a greater proportion of the vascular tree may be visualized before the polarization is lost through relaxation.
The dosages of the MR imaging agent used according to the method of the present invention will vary according to the precise nature of the MR imaging agents used, of the tissue or organ of interest and of the measuring apparatus. Preferably the dosage should be kept as low as possible while still achieving a detectable contrast effect. In general, the maximum dosage will depend on toxicity constraints.
In the following Example, the effect of temperature on the DNP enhancement and magnetisation of an ex vivo polarised water bolus is demonstrated. The agent responsible for the dynamic nuclear polarisation was a triarylmethyl free radical ("symmetric trityl") dissolved in water. ##STR1## The dynamic nuclear polarisation enhanced magnetisation at a certain proton Larmor frequency is represented as the equivalent thermal equilibrium magnetic field according to the formula:
BDNP =Enh�f/42.6 Mhz
where f is the proton Larmor frequency.
Diffusion and proton longitudinal relaxation in water may be found in J. H. Simpson et al., Phys. Rev. 111 1201-1202 (1958). Selected values are given in Table I and are field independent.
TABLE I______________________________________ Simpson et al. Diffusion constant T1Temperature D � 105 cm2 /s sec______________________________________303K 2.46 3.82313K 3.14 4.76323K 3.94 5.77333K 4.82 6.81343K 5.78 7.91______________________________________
The relaxivity of the symmetric trityl was measured on a field cycling relaxometer. The data is shown in FIG. 3. The two data series at 23� C. and 37� C. were fitted to equation 5 and the best fit parameters found to be d=5.45Å and D=DI +DS equal to 156 ps and 110 ps. Correlation times at other temperatures were found by scaling the two experimental values according to Table I for the water diffusion constant.
FIGS. 4, 5 and 6 are simulations of equations 3 and 7. Full saturation (SAT=1) of the electron spin resonance is assumed for any concentration and resonance frequency. The correlation time for each temperature is given only in FIG. 4 and is found by scaling the experimental correlation times of FIG. 3 with the relative changes in water diffusion constant. FIGS. 4, 5 and 6 illustrate that the maximum magnetisation is obtained between 10 and 20 MHz proton Larmor frequency and shifts to higher frequencies as the temperature is increased. At low frequencies, the product of r1 and T10 in equation 4 is only weakly dependent on temperature. Thus the effect of increasing the temperature is mainly to shift the dispersion point of the coupling factor to a higher frequency. However, close to and above the dispersion point of the coupling factor, increasing the temperature also has a positive effect on the leakage factor.
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|Jul 30, 2009
|Jun 2, 2011
|The Trustees of Dartmouth College noneprofit corporation
|System And Method Using Coupler-Resonators For Electron Paramagnetic Resonance Spectroscopy
|Jun 24, 2010
|Dec 29, 2011
|Johann Wolfgang Goethe-Universit�t Frankfurt am Main
|Hyperpolarisationseinrichtung und Verfahren zur Verabreichung eines hyperpolarisierten fl�ssigen Kontrastmittels
|Jun 24, 2010
|Sep 13, 2012
|Johann Wolfgang Goethe-Universit�t Frankfurt am Main
|Hyperpolarisationseinrichtung und Verfahren zur Verabreichung eines hyperpolarisierten fl�ssigen Kontrastmittels
|Sep 7, 2004
|Apr 6, 2006
|Univ Ohio State Res Found
|Nanoparticulate probe for in vivo monitoring of tissue oxygenation
|Jul 30, 2009
|May 14, 2010
|The Trustees Of Dartmouth College
|System and method using coupler-resonators for electron paramagnetic resonance spectroscopy
|Jul 30, 2009
|Jul 8, 2010
|The Trustees Of Dartmouth College
|System and method using coupler-resonators for electron paramagnetic resonance spectroscopy
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|May 27, 1998
Owner name: NYCOMED IMAGING AS, NORWAY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ARDENKJAER-LARSEN, JAN HENRIK;REEL/FRAME:009234/0737
Effective date: 19980423
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|Lapse for failure to pay maintenance fees
|Oct 19, 2004
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Effective date: 20040822


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Ralph Stanley – up close and personal
Ever wanted to share an intimate meal with the great Ralph Stanley – and 50 of his closest friends?
The good Doctor is offering just that on March 29 as a fundraiser for Song Of The Mountains, the live performance concert series aired on PBS stations across the US.
For only $250 you can dine with Stanley at the home of the President of Emory & Henry College on the campus in Emory, VA, not too far from Ralph's home in far southwest Virginia.
Only 50 reservations will be taken, so interested parties are requested to contact the Lincoln Theatre (276-783-6092 ext 2) right away.
As we have reported previously, Song Of The Mountains has run into funding difficulties in recent years, and is in danger of going dark absent new sources of revenue.
Should you wish to send a donation, they can be addressed to:
The Lincoln Theatre
P.O. Box 644
Marion, VA 24354
John Lawless
Latest posts by John Lawless (see all)
- Bobby Osborne tribute at The Paramount in Bristol - May 3, 2016
- Time to submit IBMA Special Awards recommendations - May 3, 2016
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Category: Bluegrass festival/concert news
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subset: commoncrawl


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Latest on Multimedia Entertainment »
New Delhi, Apr 3 () Passengers of Gatiman Express, India's first semi-high speed train, will not only be ushered to their seats by train hostesses and offered roses but will also be given free access to multimedia content such as movies, news and car
Union Minister for Finance, Corporate Affairs and I&B, Arun Jaitley on Monday inaugurated the Multi Media Exhibition "Saal Ek Shuruaat Anek" organized by DAVP under the aegis of Ministry of Information & Broadcasting.
Animals Are Transported To City From Various Parts Of Country And Owned Illegally. Authorities Are Not Taking Efforts To Identify Unlicenced Animals Even As They Are Being Subjected To Cruelties
Out of the many achievements of the state in all these years, significant progress has been made in the field of Marathi entertainment, especially in the recent past
Entertainment is being redefined with Tricity residents taking to virtual reality (VR). The computer based technology, in the form of goggles, places users inside the scene they are viewing.
They came with various headgears.There were Sumo wrestlers and Vikings to entertain the students at the Government Higher Primary School at Mallikatte on Thursday.
Autorickshaws plying on the city streets may soon be equipped with mobile tablets for the entertainment and safety of passengers.
BJP gave money from party fund to 'for profit' firm Shree Multimedia Vision Ltd to publish newspaper TOIBJP had given money from its funds to SMVL to publish a newspaper. Some prominent BJP leaders were either directors or stakeholders in the company.
The idea behind Ford's movie projection system is that in autonomous mode, a screen can be rolled down in front of the windshield and a movie projected on it. Ford has been calling this ' Autonomous Vehicle Entertainment System'.
Speed News
High court stays operation of a 2011 government order granting entertainment tax exemption to Tamil film with Tamil titles and promoting Tamil culture.
India Ratings & Research has revised the outlook on the media and entertainment sector to stable for 2014-15 from negative to stable as it expects improvements in advertisement spending by corporates with a gradual economic recovery. The agency expects the upcoming elections also to contribute to the increase in ad-spending in the fourth quarter of 2013-14 and first quarter of 2014-15. The agency maintains a stable outlook for most of its rated entities for 2014-15.
Indu Prakash Mishra has been appointed as advisor in the entertainment tax department. He will hold the rank of a minister of state.


text:
By Don Fry • February 24, 2009You have several options: don't quote them, paraphrase, use a partial quote, ask the question again or sharpen the answer. Read More
The Pulitzer Prizes are about to commemorate their 100th anniversary with a celebration at Poynter. In honor of the occasion, we're taking a look at exemplary social justice-focused journalism from last year and throughout the century.
This course is designed to give you the techniques and tools you need to confront complex and complicated ethical issues.Enroll Now >


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'We got to use our best people; gotta use me, but you got to use our best people. And I know the best people,' says Republican front-runner.22:52 01.05.16 | 0 comments
We have heard this anti-semitism label again and again when Israel is criticized for its actions. Lunatic politicians don't have the ability to solve problems and they resort to invoking sympathy by using these words. World had enough of it. I doubt you will get any sympathy, but you are crating a enemy for yourself.


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American comedian Soupy Sales has died at the age of 83.
The funnyman, who famously threw pies at celebrities including Frank Sinatra, Tony Curtis and Shirley MACLaine, passed away on Thursday (22Oct09) at a hospice in New York.
Sales entered the facility last week (begs12Oct09) and suffered from a number of health problems, according to his manager and longtime friend Dave Usher.
The star appeared in several U.S. gameshows throughout his career and had his own daily children's television programme, Lunch with Soupy Sales.
Continue reading: U.s. Comedian Sales Dead
Soupy Sales and Apple Friday 16th November 2007 'The Big Apple comic book, art, toy & sci-fi show' - day one, held at the Penn Plaza Pavillion. New York City, USA
...And God Spoke is a spoof about the making of a film (bad sign), a $10 million eponymous movie condensing the whole of the Bible into a feature film. Naturally, as mockumentaries demand, everything goes wrong. In the first half hour, Eve turns up with a full body tattoo, the shoot runs low on disciples, and Jesus gets cut from the film. Some of the film's moments are inspired: Namely Soupy Sales' appearance as Moses (and Lou Ferrigno vs. Andy Dick as Cain and Abel), plus a P.A.'s trunk where the film is discovered, covered in syrup. The producer and director -- Michael Riley and Stephen Rappaport -- are hysterical, deadpan and oblivious to the disaster in the making.
Continue reading: ...and God Spoke Review


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Hello im a 33 yr old ftm and im 22 weeks pregnant recently laid off and trying to stay sain but humbeling myself to ask for help.If there is anyone who has little girl clothes that they can donate i would gladly appreciate it..plz pray for me and thanks for all your supportive words on my other post
So hard to ask for help.
Posted 01/02/2013
My precious baby girl due 5/3/13
Married my best friend of 6 1/2 yrs ...11/19/12
Angels in heaven 4/2012 & 5/2005
My precious baby girl due 5/3/13
Comments (9)
Posted 01/03/2013
Try Goodwill or consignment shops. Also check craigslist.
Proud Mommy & Daddy to Autumn Rose 4.29.13
Lindsay (25) & Mike (27)
Together since May 23, 2011
Proud Mommy & Daddy to Autumn Rose 4.29.13
Posted 01/03/2013
Try churches. My friend donates all her stuff to her church & they give it away.
Stephen & Brandi married 10/14/2006 Caleb born 36w 1/2/2009
two angels 3/2011 & 6/2011
Angel Elijah born sleeping 28 weeks 3/8/2013
Posted 01/03/2013
I second churches. There's one in my area that gives away clothes and food once a week. I'm sure there will be something like that in your area. I'm not sure how tight on money you are but I buy from thrift stores on their half off day and usually outfits are only .50. I'm so sorry and will pray for you. Many of us have been or are in that situation
Posted 01/03/2013
Oh also try freecycle.org. It's where people give away stuff they don't want. You can also post for things you need. I'm sure there are people in your area happy to get rid of their old baby clutter.
Posted 01/03/2013
I run a nonprofit and we collect baby and kids items and give them away to families in need. Where do u live? Message me. I have a storage unit full of stuff.
Learn more
Look how far your child has come.
Review your child's growth milestones.
Read about 34 months : Week 4.
Your growing child
Your 35-month-old: Preferring one parent
Try not to take it personally if your 35-month-old prefers his other parent. Read More
Your 35-month-old: Why preschoolers lie
For preschoolers, the line between fantasy and reality is blurry, which may explain their tendency to lie. Read More
Your 35-month-old: Riding a bike
Most children master a tricycle between ages 2 and 3. It takes large-muscle power and coordination to manage this feat. Read More
Your 35-month-old: Collecting
Older preschoolers are as passionate about collecting things as adults. Read More
Your 3-year-old: Imaginary friends
Been asked to set an extra place at dinner for an imaginary friend yet? As many as half of preschoolers have a pretend buddy. Read More
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What's next for your growing child?
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Read about 3 years : Week 1.


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Dawson's Creek 1998 | TV Show Watchlist
Season 6, Episode 1 The Kids Are Alright
First Aired: October 2, 2002
Dawson makes an unexpected trip to Boston to visit Joey after spending the summer apart. Audrey and Pacey return from L.A. and Pacey looks into a new job prospect that could change his relationship with Audrey. Meanwhile, Jen is surprised to learn that Grams is in her art history class. Grams: Mary Beth Peil. Pacey: Joshua Jackson. Jen: Michelle Williams.
Cast & Details See all »
- Premiered: January 20, 1998
- Rating: None
- Premise: A popular and cool teen soap about attractive, very self-aware young people in a Boston suburb (though it was filmed in North Carolina). Full of the clever pop-culture references that are a trademark of creator Kevin Williamson ('Scream'), who based it in… (more)
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heidi beirich
heidi beirich: Page 1
Brave New Foundation, Rachel Maddow think you're gullible (FAIR, immigration, SB1070) - 04/25/12
The video below shows Rachel Maddow and Robert Greenwald's Brave New Films thinking you're a gullible sucker in at least two ways.
Liza Mundy /WaPo lies about Obama certificate (+SPLC joins in) - 10/06/09
Liza Mundy of the Washington Post offers "Burden of Proof on Obama's Origins" (link), a three-screen, mostly smear piece on Orly Taitz of the "Birthers" movement. Leaving aside Taitz' various claims, Mundy has a problem with the truth. (Note that she's also the author of a presumably sympathetic biography of Michelle Obama; she whines about the lack of cooperation from the Obama camp at slate.com/id/2202261).
Mundy quotes Taitz as saying of Obama's records "Nobody has seen proper documents. Period." and follows that with this:
Another breathtaking statement, or rather misstatement. After initially trying to ignore the controversy, Obama's staff has indeed provided an official record showing that the president was born in Hawaii. The document is a computer-generated official certification of live birth attesting to the fact that Barack Hussein Obama II was born on Aug. 4, 1961, in Honolulu. The director of Hawaii's Department of Health also has stated, rather wearily, that she has viewed the underlying vital records and that they are valid.
All Obama has provided is a picture of what looks to be an official document; he hasn't provided the document itself as Lisa Munday states. The picture has never been authenticated by any government agency, and thus there's no proof that anything on it is accurate. While Chiyome Fukino of the Hawaii Department of Health did say in 2008 "the Hawai'i State Department of Health has Sen. Obama's original birth certificate on record in accordance with state policies and procedures" and then in July she said that she's "seen the original vital records maintained on file by the Hawai'i State Department of Health verifying Barrack Hussein Obama was born in Hawaii and is a natural-born American citizen", she didn't say anything about the picture on Obama's site, as Mundy is implying.
Mundy also (of course) plays the race card and the extremist card:
At a minimum, organizations who monitor extremist groups say that the fantasy of Obama's ineligibility is now a central tenet. "The birther conspiracy itself is now totally widespread among military and paramilitary [militia] groups and new, what we would call quote-unquote 'patriot' groups, which are groups that are virulently anti-government," says Heidi Beirich, director of research at the Southern Poverty Law Center. Beirich says that a popular conspiracy theory among such groups is that the government is going to round up citizens and put them in camps operated by the Federal Emergency Management Agency.
SPLC names "hate group" based on something they didn't promote - 04/10/09
The Southern Poverty Law Center publishes a list of "hate groups" which includes both true hate groups as well as those who simply disagree with the SPLC's support for illegal immigration and the like. That would be insignificant if it weren't for the fact that the mainstream media as well as even government agencies take them seriously.
Dennis Roddy /Pittsburgh PG, SPLC, LGF, HotAir, Kos use tragedy to smear opponents - 04/05/09
Dennis Roddy of the Pittsburgh Post Gazette offers "Suspect in officers' shooting was into conspiracy theories" (link) about the recent shooting of three police officers in Pittsburgh by an obviously deranged 22-year-old. He takes advantage of that tragedy to smear his or his paper's opponents:
Mr. Poplawski's view of guns and personal freedom took a turn toward the fringes of American politics. With Mr. Perkovic, he appeared to share a belief that the government was controlled from unseen forces, that troops were being shipped home from the Mideast to police the citizenry here, and that Jews secretly ran the country.
...Believing most media were covering up important events, Mr. Poplawski turned to a far-right conspiracy Web site run by Alex Jones, a self-described documentarian with roots going back to the extremist militia movement of the early 1990s.
He was also a member of Stormfront. Ergo, in Roddy's mind, Alex Jones = Stormfront. And, whatever Jones' ideology, I don't think "far-right" is accurate. And, while Jones is "out there" a good part of the time, he's also had a couple scoops about things that sounded loony but which turned out later to be true.
Regarding the troops, see December's "20,000 U.S. military troops to help with "homeland security" in U.S. by 2011", which links to a Washington Post article about such a scheme. That was also discussed in September; the Army Times and the underlying documents included the possibility of using troops for crowd control.
One of the shooter's friends alludes to media bias regarding the MSM not covering states recently declaring sovereignty with the implication that there is no such bias. There's a round-up here from the Christian Science Monitor; Google News wasn't exactly filled with similar MSM articles. A smaller paper covered the movement in Pennsylvania here, a story that I couldn't locate at the Post-Gazette's site.
In case you think Roddy is just presenting facts without attempting to smear, he continues with this:
"For some time now there has been a pretty good connection between being sucked into this conspiracy world and propagating violence," said Heidi Beirich, director of research at the Southern Poverty Law Center and an expert on political extremists. She called Mr. Poplawski's act, "a classic example of what happens when you start buying all this conspiracy stuff."
Meanwhile, over at HotAir, one of their staffers links to the Little Green Footballs entry [1] with the title "Surprise: Pittsburgh cop-killer was anti-semitic, white supremacist, Alex Jones fan".
Over to Ed Morrissey at the same site (hotair.com/archives/2009/04/05/kos-conservatives-like-to-shoot-cops):
Those who would use such horrifying tragedies to smear their political opponents are completely unworthy of engagement, and utterly despicable to boot, regardless of which side they're on.
[1] littlegreenfootballs.com/article/
UPDATE: Also, as discussed at the last HotAir link, Kos said on twitter that "Conservatives, apparently, prefer to talk "revolution" and shoot cops." He may have just been "joking".
UPDATE 2: The Anti Defamation League has also gotten involved in the smear; that and the other issues above are answered in "Poplawski Smear Debunked: Cop Killer Held Opposing Views To Infowars" (link).
UPDATE 3: Both RawStory and a DailyKos blogger have retracted Alex Jones-related smears (link). However, Sean Hamill of the New York Times and Eric Boehlert of Media Matters for America continue the smear (link, link).
SPLC tries to stifle FAIR (Mexico links, CAP) - 12/11/07
Heidi Beirich of the Southern Poverty Law Center offers "The Teflon Nativists/FAIR Marked by Ties to White Supremacy" (splcenter . org/intel/intelreport/article.jsp?aid=846) with the news that it's "official": the SPLC has declared the Federation for American Immigration Reform (FAIR) to be a "hate group". They mention how much press coverage FAIR has received, and they include a quote from Henry Fernandez of the Center for American Progress which helps show that their goal is to stifle FAIR:
"The sad fact is that attempts to reform our immigration system are being sabotaged by organizations fueled by hate... Many anti-immigrant leaders have backgrounds that should disqualify them from even participating in mainstream debate, yet the American press quotes them without ever noting their bizarre and often racist beliefs."
I'd imagine that the MSM will just eat this up without even looking into it, resulting in fewer press mentions and a reduced voice for those of us who support our laws. I'll let FAIR speak for themselves (if they deign to do so), but I'll point out a few things:
1. The SPLC is indirectly linked to the Mexican government (see their name's link above); I've never seen that mentioned in any of the "news" reports that take them as a semi-official source. Fernandez is also indirectly linked to that government (see his name's link).
2. Part of their designation rests on the fact that FAIR has received funding from an "infamous, racist eugenics foundation." That's a reference to the Pioneer Fund; in the same decade as they gave money to FAIR they also gave money to Stanford, the Tel Aviv University, the Sickle Cell Disease Foundation of Greater New York, and others.
3. Another part is because FAIR has supposedly put forth "racist conspiracy theories about Mexico's secret designs on the American Southwest". I don't know what FAIR has said, but the Mexican government has explicitly stated that they want to meddle in our internal politics and will be using non-profit organizations to do so. That translate to obtaining political power inside the U.S. and, should that process not be stopped, some form of de jure or de facto condominium.
4. Yet another part is because FAIR supposedly has an "alternative theory alleging secret plans to merge the United States, Mexico and Canada". I guess the SPLC missed Congressional testimony from an elite group advocating for that scheme, and all the other flashing neon signs pointing in that direction: North American Union.
UPDATE: FAIR responds with just some of the things the SPLC got wrong here. Note especially this:
In light of the fact that FAIR has requested the SPLC to correct these errors on at least three different occasions dating back to 2001, the publication of this erroneous information appears to be willful and malicious.
UPDATE 2: On a sidenote, the SPLC's Intelligence Report has won the 2007 "In-Depth/Investigative Reporting" award from the Utne Reader (utne.com/print-article.aspx?id=13124).


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2K sports has announced that they are brining their much loved Top Spin franchise to the Wii in a move that is being herald as a follow up to the success of Wii Sports
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Daily Archives: 21 May 2014
Mini-Sabbatical Coming Up
I can hardly believe it is nearly time for me to take a five-week leave of Ames, Iowa and the parish and student center where I serve. Thanks to generous grants from the archdiocese and from an endowment set up … Continue reading
Posted in spirituality 8 Comments
Bad Liturgy 1: Reserving the Blood
If I were to start blogging today, maybe I would title my site "Bad Liturgy." Why? I reflect on a few recent practices in my parish and I think about how much worse it was in the past. I just … Continue reading
Posted in Liturgy 3 Comments
Reconciliation Lectionary: Ephesians 2:1-10
Section 157 in the Rite of Penance gives a long section of Ephesians 2 as an option for a reading. As with other reflections in this series, we'll look at the passage not as a Bible Study as such, but … Continue reading
Posted in Rite of Penance, Scripture Tagged Bible, penance, reconciliation Leave a comment
Dies Domini 62: Sabbath Fulfilled
Christians do not keep the Jewish Sabbath. But the roots of the Torah are found in God's liberating act of the Exodus. God cares for us, liberates and saves us. This suggests, invites, beckons a response on the part of … Continue reading
Posted in Dies Domini, post-conciliar liturgy documents 1 Comment
Signs At The Top … Or Near The Top
When it's not a matter of doctrine, Cardinal Joao Braz de Aviz is really the red hat who oversees women religious. Or he's supposed to be. He seems to want the LCWR/CDF parties to play nice. He insists people aren't … Continue reading
Posted in bishops, Church News, Commentary, Politics, women religious 3 Comments
Children, Not As Pawns
I noticed Archbishop Chaput's facebook post protesting the striking down of the gay marriage ban in his state, which included this bit about children: Marriage is more than a private arrangement between two people. It's a public commitment of love … Continue reading
Posted in Adoption, bishops, Church News, Commentary, Politics Leave a comment
EG 180: The Kingdom and Its Challenge
A brief section of Evangelii Gaudium today, in which Pope Francis offers the first half of a discourse on "The kingdom and its challenge." As we've heard, the Church is not a personal encounter experience nor is it a public service organization: … Continue reading
Posted in Evangelii Gaudium, evangelization Tagged pope francis Leave a comment


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Angels homestand first pitchers, promos
Scott Spiezio and Jarrod Washburn of the 2002 World Series champion Angels return along with legends Buck Rodgers and Bobby Knoop during this homestand from Monday, Aug. 15 to Wednesday, Aug. 24. Christian rockers MercyMe plus two of the most anticipated giveaways – the Angels Gnome Bobblehead and the Rally Monkey Chia Pet – appear in this nine-game stretch.
Check out the slide show for a game-by-game preview of upcoming Alumni first pitchers and promotions.
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Sunday, December 22, 2013
OKANOGAN More than 300 new and gently used toys were collected by Okanogan High School National Honor Society members and donated to Okanogan County Community Action.
The students collected "boxes and boxes and boxes" of toys, adviser Trisha Bradley said. About a third of the toys were collected during the middle-high school concert last Wednesday.
Along with commercially made toys and games, the donations included several wooden trucks made by members of Andy Knutson's middle school wood shop class.
The group also collected more than 75 rolls of gift wrap and 30 rolls of tape.
Community Action Executive Director Lael Duncan said the toys will be distributed Monday morning to her agency's clients.
Toys and presents collected by Kinross Gold Corp. employees also will be given.
"The community really turns out at Christmas time," she said.
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Reflex Marine, dedicated to the transfer of personnel to and from offshore installations and vessels, has appointed a new board member to help meet the demands of global growth, particularly in the , and diversification of the company's products and service portfolio.
David Brittan, a graduate of mechanical engineering from , began his career as a drilling engineer with BP in 1987. He has since worked with a number of major oil and gas companies, with considerable international experience.
He held the position of Worldwide Well Engineering Manager for BG Group and a coordinating role on the giant Karachaganak project in . He has worked in key markets across the globe, including , and .
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Chevron Corp. reported a first-quarter loss as slumping oil prices continued to drag down revenue. The company said that it is "on target" to lay off a total of 8000 workers by the end of 2016,
China COSCO Shipping has won the draw for its container vessel Andronikos to make the ceremonial first transit through the Expanded Panama Canal during the waterway's inauguration on Sunday, June 26.
On April, 20, 2016, at the young age of 97 years, Walter Sellick along with sons Howard Sellick - President, David Sellick - Vice President and grandson Colin Sellick - Systems Manager,


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Explore: Videos
October 10, 2012
Ben Jealous at the 16th Annual HRC National Dinner
The NAACP and its president, Ben Jealous, were honored with the National Equality Award for their steadfast support for LGBT equality, including their public support for same-sex marriage earlier this year.
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Reviews of Beyond the Black Rainbow 2010
Kubrick is alive
As an exercise in style and atmosphere it's well done. Everything else about it was lacking so it's definitely one where there's a lot of style, but not a lot of substance.
lol i love vsco cam! toaster filter mm
I had high hopes. I'm just upset that this movie put so much thought into its look and its aesthetic and its design that it completely ignored any trace of a plot. Yeah there's a premise (albeit not really an interesting or original one), but we float through complete nothingness for a very, very long time before anything really happens. And even when that happens, does it really?…
Atmospheric and unsettling. Paced incredibly slowly which builds a lot of tension that results in some eerie and at times horrifying imagery. I loved how it was shot and it reminded me of a Kubrick world.
One star for the John Carpenter-esque soundtrack.
I could not make it through this.
There is a magical moment that comes when you are watching or reading something weird and abstract, that moment where you suddenly connect with the creator of that weirdness and you "get it". I love that second, when you feel a little superior to all those other fools out there who don't "get it", the "squares" Daddy-O!. I kept waiting for that brief flash when I would be drawn into this strange, dark and indecipherable movie. It never came. I…
"Beyond the Black Rainbow" is not a movie that I can usually recommend to most people due to its deliberately slow pacing and focus on psychedelic freak show visuals over any kind of coherent story. But I can't help but love it; it's a clear tribute to some of the masters of the genre (Tarkovsky and Kubrick chief among them) and has the look and feel of some long-lost early-80s midnight art film. Provided you're in the right mindset (which may or may not necessitate the use of a controlled substance), there's plenty to appreciate here.
I have to watch this again. Didn't do a heck-of-a lot for me the first time but that's probably because I was tired as shit.
Consider this, with The Strange Colour of Your Body's Tears things that I have to rewatch again.
In all honesty, I couldn't bring myself to finish it. I don't even know what the 2 stars are for. Well, I do like the cover art and the opening sequence. There.
Beyond The Black Rainbow is a stylish retro, psychological thriller that explores the sacrifices men will make on their search for inner peace and enlightenment. The first act is very slow and not much happens, the second act gets more interesting as it begins to explore the existential horror of enlightenment through a flashback sequence that shines more light on the plot and the motivations behind the first act. The third act is where things get really intense and where…
Long on stretching what can be done visually with simple tricks like messing with focus and contrast (with a serious side business in finding a myriad of ways to make Michael Rogers' face look even more uncanny than it already is) but short on anything like a compelling or even mildly interesting story. I wanted to like this a lot more than I did.
Goes nowhere at a snail's pace, steals from much better sources. Sounds great though, surround really hums. Get buzzed and throw on some Tangerine Dream for a less aggravating experience.


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Spring is the perfect time to stock up your library. Save big when you purchase now!
From choosing deck materials to complementing the architecture of your house, this book covers the deck design process, enabling you to create a custom deck that's perfect for your home.
Mid-Atlantic Gardener's Handbook offers information on annuals, perennials, edibles, and more for passionate gardeners living in the Mid-Atlantic region. With monthly tips and critical when-to-do-it information, this is a must-read.
Gardening on a Shoestring offers readers budget-friendly tips for creating beautiful gardens. By demonstrating creative projects, growing techniques, and up-cycling ideas, the book is a fabulous resource for the cost-conscious gardener.
Author Diana (Dee) Maranhao brings over 30 years of experience to help you create the garden of your dreams and save water at the same time.


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René de Vries has been appointed (State) Harbour Master of Rotterdam, taking office on 1 March 2010. That is the date on which the current Harbour Master Jaap Lems retires. The port of Rotterdam is not unknown territory for De Vries. He began his career with the Port Authority in 1982, as crew member on one of the patrol vessels. Through the years, he has progressed to his present position, as manager of the Traffic Planning & Operations department, which has 220 staff.
The (State) Harbour Master is responsible for the fast, safe and clean handling of shipping traffic in the port of Rotterdam. Under his direction, around 570 people work, among other things, in traffic control centres, the Port Coordination Centre, bridges and locks, on patrol vessels and as inspectors on board visiting ships. This work is largely done around the clock. On one hand, the (State) Harbour Master forms part of the Port of Rotterdam Authority and, on the other, is accountable to the Municipal Executive and the Minister of Transport, Public Works and Water Management with respect to his public duties. The Harbour Master is also port security officer and forms part of Rotterdam's security staff.
In careful consultation with the municipality of Rotterdam and the Ministry of Transport, Public Works and Water Management, the Port Authority started to look for a new (State) Harbour Master this spring. Following an exhaustive internal and external selection procedure, René de Vries was chosen, due to his combination of experience, knowledge and personality.
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Port congestion eases at Basra and Chinese ports; tanker demand set to expand on lower oil prices.
Freight rates for very large crude carriers (VLCCs), hurt by slower-than-usual release of cargo,
The European Commission said on Friday it had cleared French shipping group CMA CGM's $2.4 billion takeover of Neptune Orient Lines on condition that NOL pulls out from a rival shipping alliance.
WILCO Logistics Pty Ltd has been announced as the successful bid contractor on Breakwater safety works at the Port of Townsville.
Minister for Ports Mark Bailey said the overall $1.
At a meeting of the International Oil Pollution Compensation Funds (IOPCF) this week, the International Chamber of Shipping (ICS) has strongly criticised the judgement
Cargotec's January-March 2016 interim report: Profitability improved according to target
* Strong order intake in Kalmar and Hiab
* MacGregor profitability


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Hay everyone I have a question I'm pregnant and when I went to the dr they said my levels droped I was only a week I went back about a week or two later n my levels shot up could it have been possible I was having twins and I lost one? I go back Friday for another ultrasound n blood level check for my hormones
first child
Posted 03/28/2013
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Breaking my vows of secrecy for you
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I know that speaking out this truth will be extremely difficult for people to accept. The majority will not believe it. It will be attacked by other members of the groups I speak out from. Nevertheless, I feel it my obligation to inform you all of what I know - and at least I have done my part, regardless of whether you believe it or not.
So I will continue.
There is a war going on for your Soul, and your Mind. This war has already been close to won , and your souls and minds are in most cases hopefully lost. There is still hope though, as the forces of good beyond the Sphere in which you exist are still fighting the cause for you. Again I like to draw analogies to what we have around us here on Earth, and since I already mentioned farm animals, I will describe it like this:
The animals in the farm do not know what is going on in their reality. They do not know there is a reality beyond what they experience. They take what they have for granted. Indeed, many of them do not even suffer, they may quite enjoy where they are. Yet, they are not free, nor are they experiencing their fullest or most true selves. And for that, you have activists that raid the farms, and laboratories - a place even closer to what it really all is about - to set free those animals, and help them escape from where they are living in capture. These animals do mostly not know they live in capture, they dont know the world outside, so once they DO get out, they are confused, and stumble around, do not know where to go - and most of them fall and very few actually ends up free. But, now and then once in a while, a few of them manages to get into the real woods, beyond the limits of the city they were trapped within, and experience their true natural surrondings, and gets to know what they really are and where they came from.
And the same goes for you people here - you are like those animals, and there are those other beings out there which have the role as the "activists" trying to set you free. You do not know this, you are not aware of them, nor do you know that you are not free, or that all you know as Reality, and even Yourselves, are nothing but illusions. They are still out there, working behind the scene, to try lead you back home from where you came.
Just as there is a problem for an activist to explain an animal that it is captured, and what its freedom really is, and where it comes from, there is an equal problem for those beings beyond to explain the same to you people. Yet, your ignorance, and inability to understand, does not make the truth cease to exist. It still remains as it is.
Some of you will feel a wave over you as you read this, this is the wave of truth, intuition, that part of you still connected to your true Soul, your real being. However, most of you are so indoctrinated, mind controled and brainwashed that you will think of it all as utter nonsense, lies and fabrications. And that is fine, it is not your fault, and the truth IS hard to grasp.
You have been here so long, that you hardly know anything else, not even in the depths of your spirits, since you have in fact lived over and over here from generation to generation, from lifetime to lifetime, making you so tied to Earth and physical existence the way you experience it now, that you will have a hard time letting go and be free, or even know that there ever was anything else.
Of course, the idea about reincarnation is something everyone have heard of, and nothing new for most of you. But, the TRUTH behind reincarnation is probably not that familiar to you. And the truth is that reincarnation exists to KEEP you here, NOT to make you progress or develop in any way at all. It is part of the many chains that drags you back down life after life, it is between each incarnation you are abused mentally, mind controlled, having your memories erased and forced into an amnesia removing your knowledge of self and individuality. Reincarnation, as well as Karma - they are, as with everything else, falsely explained in the "public" and religous teachings of Earth, since EVERYTHING here is made to keep you here and away from the Truth as I mentioned in the introduction.
You whole physical body is a creation, artificially designed, to capture your soul within it, and deny you access to the higher form of existence where you are truly from.
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