text:
|Publication number
|Publication type
|Application number
|Publication date
|Jan 4, 2011
|Filing date
|Jan 30, 2008
|Priority date
|Feb 9, 2007
|Fee status
|Also published as
|Publication number
|Gangming Luo, Jonathan J. Kaufman
|Original Assignee
|Cyberlogic, Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (54), Non-Patent Citations (19), Referenced by (2), Classifications (7), Legal Events (2)
|External Links: USPTO, USPTO Assignment, Espacenet
This application claims priority to Provisional Application No. 60/900,599, filed Feb. 9, 2007, the entire disclosure of which is incorporated herein by reference, and claims priority to Provisional Application No. 60/907,000, filed Mar. 14, 2007, the entire disclosure of which is incorporated herein by reference.
The present invention relates generally to apparatus and method for non-invasively and quantitatively evaluating bone tissue in vivo. More specifically, the invention pertains to osteoporosis diagnosis and bone fracture risk assessment using multiple ultrasonic features in a portable ultrasonic device.
In recent years, ultrasound has received a great deal of attention as a new technique for noninvasive assessment of bone, and numerous attempts have been made to use ultrasound energy for evaluating the condition of bone tissue in vivo, and thus for determining a measure of osteoporosis and assessing bone fracture risk.
In particular, Hoop discloses in U.S. Pat. No. 3,847,141 a device to measure bone density as a means for monitoring calcium content of the involved bone. A pair of opposed ultrasonic transducers is applied to opposite sides of a subject's finger, such that recurrent pulses transmitted via one transducer are "focused" on the bone, while the receiver response of the other transducer is similarly "focused" to receive pulses that have been transmitted through the bone. The circuitry in Hoop is arranged such that filtered reception of one pulse triggers the next pulse transmission; the filtering is by way of a bandpass filter, passing components of received signals in the 25 kHz to 125 kHz range only; and the observed frequency of retriggering is believed to be proportional to the calcium content of the bone. Thus Hoop is concerned only with what he defines to be transit time for pulses in the indicated band.
Pratt, Jr. deals with establishing, in vivo, the strength of bone in a live being such as a horse. In U.S. Pat. No. 4,361,154, the inventor solves the problem posed by measuring transit time from "launch" to "reception" of pulses of 0.5 MHz and 1.0 MHz through the bone and soft tissue, and from measurement of pulse-echo time, to thereby derive a measurement of transit time through bone alone. A data bank enables the evaluation of the bone condition from the measured transit times. U.S. Pat. No. 4,913,157, also granted to Pratt, Jr., operates on the same general principle of transit time/velocity deduction, using the latter preferred frequency of 2.25 MHz as the base frequency of pulsed "launchings" and a technique of matched filtering/Fourier transform filtering for further analyzing received pulses.
Palmer et al. disclose in U.S. Pat. No. 4,774,959 a bone measurement system deriving the slope of the relation between ultrasonic frequency and attenuation of a sequence of tone signals. Being in the range of 200 kHz to 600 kHz, the signals are applied to one transducer and received by another transducer. The passage of the signals between the two transducers with and without the intervening presence of a heel bone is compared, with the assumption that the frequency/attenuation relation is a straight line, i.e., of constant slope.
U.S. Pat. No. 4,926,870 granted to Brandenburger discloses another in vivo bone analysis system which depends upon measuring transit time for an ultrasonic signal along a desired path through bone. A "canonical" waveform, determined by previous experience to be on the correct path, is used for comparison against received signals for transmission through the patient's bone, while the latter is reoriented until the received signal indicates that the bone is aligned with the desired path. Again, ultrasonic velocity through the patient's bone is assumed to have been determined from measured transit time.
Rossman et al. disclose in U.S. Pat. No. 5,054,490 an ultrasound densitometer for measuring physical properties and integrity of bone, upon determination of a transit time through bone. Alternatively, the Rossman et al. device compares absolute attenuation of specific frequency components of ultrasound signals through the bone with the absolute attenuation of the same frequency components through a medium of known acoustic properties.
Mele et al., disclose in U.S. Pat. No. 5,564,423, and in a subsequent related patent by Cadossi et al. (U.S. Pat. No. 6,436,042), disclose a device that measures the "amplitude dependent speed of sound" through a bony member in a living body. The method relies on the visual display of the received ultrasound signal, and the selection of a specific portion of the waveform for analysis.
The prior art, exemplified by the above references that have been briefly discussed, proceed on the assumptions that transit time and velocity—as well as the assumed linear slope of attenuation as a function of a set of discrete frequencies—are all-important in assessing bone. These approaches have essentially been ad hoc, with no consistent framework within which to analyze data. Despite the fact that a rich variety of information is obtainable from experiments with ultrasound (including computer simulations as well as in vitro and in vivo experiments) and that a variety of analytic results are available as well, much of the information has not been used and available, and useful aspects of the data have been ignored.
Significant steps forward in this direction have been made by Kaufman et al. (in U.S. Pat. Nos. 5,259,384 and 5,651,363) and by Chiabrera et al. (in U.S. Pat. Nos. 5,785,656 and 5,879,301). In these patents, an estimate of a "bone transfer function" associated with a given bone is obtained in a statistically optimal fashion, and parametric estimates of the phase and attenuation functions associated with it are determined. The disclosed methods also describe the use of 2D array transducers for obtaining more reproducible estimates of the bone density, architecture, and fracture risk.
Notwithstanding the advances made in the last-mentioned apparatuses and methods, there are still additional improvements needed in order to accurately and precisely assess the bone density, architecture, quality and fracture risk of a subject. While ultrasound is said to having great potential to assess the biomechanical strength of bone—since it is a mechanical wave in contrast to the ionizing radiation of standard x-ray densitometers—until now much of this potential is unrealized.
It is accordingly a primary object of this invention to provide an improved method and apparatus for characterizing and determining non-invasively the properties of bone. A more particular though not limiting object of the invention is to provide a method and apparatus for non-invasive and quantitative evaluation of bone tissue in vivo, to make accurate osteoporosis diagnosis and monitoring possible.
Another object is to meet the above object in such a way that the bone tissue evaluation and the osteoporosis diagnosis may be performed with relatively more simple and efficient means than those previously used.
A further object is to meet the above objects by providing more accurate and precise estimates of bone mass, bone density, bone geometry, bone quality, and bone strength, as compared with means disclosed previously.
A still further object is to meet the above objects by providing methods to obtain new ultrasound parameters which are sensitive to both bone mass, bone geometry, and bone strength.
A yet still further object is to provide an enhanced ability to estimate the fracture risk associated with a given living being.
As compared with the prior art, the invention incorporates information from the ultrasound measurements that is crucial to achieving the indicated objectives. In particular, the present invention is based on using neither only a time delay nor only a velocity, but a unique combination of a set of three time delays, that is superior to the approaches disclosed in the prior art. Further, these prior approaches neither appropriately nor adequately characterize the bone being assessed, and therefore cannot meet the objectives of the present invention.
Accordingly, the present invention utilizes a new processing algorithm to capture much more information from the ultrasound measurements, to more accurately and precisely determine the characteristics of the interrogated bone—to thereby determine one or more of the bone properties such as fracture risk, strength, density, mass, quality, and/or geometry of the bone. The advantage of such an approach is its inherent and increased sensitivity to the underlying state of the interrogated bone. This is in contrast to the prior art which cannot extract as much information on the underlying bone since they do not utilize optimal and model-based processing.
The invention in its presently preferred form of a method of non-invasive and quantitative assessment of the status of a bone tissue in vivo for one or more of the quantities: bone-mineral density, bone mass, geometry, strength, quality, and fracture risk, achieves the foregoing objectives by acoustically coupling a pair of transducers to nearby skin surfaces on opposite sides of a bony member; generating an ultrasound signal and directing this signal from one transducer to another transducer of the pair of transducers through the bony member, thereby producing a bone-oriented output signal, the ultrasound signal being a finite-duration signal repeated substantially in a range from 1 to 5000 Hz and consisting of plural frequencies spaced in an ultrasonic spectral region up to about 10 MHz; processing the bone-oriented output signal to obtain at least two (2) net time delay (NTD) parameters, and further processing the at least two NTD parameters to obtain an estimate of the one or more said quantities.
The step of further processing may be performed with the use of one or more of a plurality of associated parameters: age, sex, fracture history, bone mineral density as measured by x-ray absorptiometry at a given anatomical site, cigarette smoking history, height, and weight that is specific to an individual subject. The step of further processing may be performed with the use of multivariate linear and nonlinear regressions, a statistical hypothesis testing algorithm, and may include a neural network configured to generate an estimate of the one or more of the quantities from the parameters and from the associated parameters specific for an individual patient.
In its presently preferred apparatus form, the invention comprises transducer means including a pair of ultrasonic transducers adapted for acoustic coupling to nearby skin surfaces on opposite sides of a bony member; and for transmission through an ascertained acoustic propagation path which includes a bony part of a living body; a generator means for connecting to a transmission transducer of the pair to generate an ultrasound waveform, this waveform being a finite-duration signal consisting of plural frequencies spaced in the ultrasonic spectral region to approximately 10 MHz and being repeated substantially in the range from 1 Hz to 5000 Hz; and a signal-processing means that are connected for response to the signal received by a receiving transducer of the pair and comprise means to provide analog-to-digital sampling and signal processing of the bone-oriented output signals, to thereby produce corresponding parameters and means for performing further analysis of the parameters resulting in estimates of bone properties.
In the presently preferred embodiment of the invention, and with additional reference to
In the presently preferred embodiment of the invention, the three time delays are then further processed to obtain a set of two net time delay (NTD) parameters, NTDa and NTDb. The NTD parameters are differences between the three time delays described supra. In particular, NTDa=τ1−τ2 and NTDb=τ2−τ3. In the presently preferred embodiment of the invention, the NTDa and NTDb are further processed to accurately and precisely determine the characteristics of the interrogated bone—to thereby determine one or more of the bone properties such as bone mass, bone density, cortical thickness, cross-sectional area, medullar thickness, strength, quality, and/or fracture risk of the bone. It should be appreciated that other pairs of net time delays could be defined from the set of three time delays defined supra; however these are in fact all equivalent (that is, any set of two net time delays are equivalent to any other set containing two net time delays derived from the three time delays), and thus any two net time delays are considered to be within the scope of the present invention.
In the presently preferred embodiment of the invention, the bone mineral density (BMD) of the bone in the bony member is evaluated according to a regression between BMD on the one hand, and NTDa and NTDb on the other. This regression is given by BMD=a NTDa�NTDa+b NTDa�NTDb+c, where a, b and c are regression coefficients obtained by the method of least squares. It should be understood that a similar equation can be used to estimate the cross-sectional area, but with different regression coefficients. In addition, an estimate of cortical thickness (CT) may be estimated by CT=e NTDa+f, where e and f are regression coefficients obtained by the method of least squares. It should further be appreciated that the size of the medullar canal (medullar thickness or MT) may be estimated by MT=g NTDb+h, where g and h are regression coefficients obtained by the method of least squares. It should be appreciated that any kind of processing of either the set of three time delays or a set of two associated net time delays should be considered to be within the scope of the present invention. For example, it may be useful in certain embodiments to use a ratio of two net time delays in estimating bone mass, geometry, strength, and/or fracture risk. In other cases, it may be preferred to use other nonlinear (or even linear) combinations of two net time delays or of the three time delays.
An apparatus for the preceding embodiments is shown in
The invention is shown in
Referring to
Basic operation is governed by a computer means 20, which may be a personal computer, such as the Dell Precision Workstation 670 available from Dell, Inc., Round Rock, Tex.; this computer contains an Intel Xeon Processor running at 3.60 GHz, with provision for keyboard instruction at 22.
An arbitrary-function generator card 24 is shown installed in the computer 20. This card is relied upon to generate an excitation signal which is periodically supplied to the launch transducer 16, via a power amplifier means 26. The power amplifier 26 is suitably the Model No. 240L, an RF power-amplifier product of EIN, Inc., Rochester, N.Y. This amplifier provides a 50 dB gain, over the range 20 kHz to 10 MHZ. In addition to power amplifier means 26, the excitation signal must pass through a switching network 27 a in an alternative embodiment using multi-element, linear- or two-dimensional array transducers, described fully infra.
The excitation signal generated by the card 24 is a finite-duration pulse that is repeated substantially in the range from 1 to 5000 Hz. The card 24 may suitably be a waveform synthesizer, a product of PC Instruments, Inc., Lawrence, Kans., identified by PC Instruments part No. PCI-341. The waveform synthesizer provides generation of analog signals independent of the host computer 20, that allows full processor power to be used for other tasks, including calculation of waveform data.
Another card 28 is shown installed into the computer 20 for converting signals received at the receiving transducer 18 into a digital format for further processing in the computer 20. The card 28 may suitably be a 200 MHZ 14 bit waveform digitizer, a part known as Compuscope 14200, a product available from Gage Applied Technologies, Inc., of Montreal, Quebec, Canada.
As with the launch transducer 16, in an alternative embodiment described more fully infra, where receiving transducer 18 is a multi-element, linear or two-dimensional array transducer, a switching network 27 b must be placed between the receiving transducer 18 and the card 28 of computer 20.
Also, general signal-processing/display/storage software, for the signal processing control and operation of the computer 20 is not shown but will be understood to be loaded at CD drive 34 into the computer 20; this software is suitably MATLAB for Windows, available from The Math Works, Inc., Natick, Mass. Further software, also not shown but loaded into the computer 20, are the Neural Network and Optimization Toolboxes, also from The Math Works as well as software (drivers) for interfacing the cards in the computer, available from Gage Applied Technologies and PC Instruments. In addition, a Visual C++ compiler, preferably one available from Microsoft Corporation (Redmond, Wash.) is also understood to be loaded into the computer 20.
In the presently preferred embodiment, involving the described components of
In this embodiment, as may be understood the two transducers consist of a first transducer and a second transducer acoustically coupled to nearby skin on opposite sides of a bony member (i.e., bone tissue surrounded by overlying soft tissue). The arbitrary-function generator card 24 and power amplifier 26 are used to produce an electrical input signal which is applied to the first transducer. This causes an ultrasound signal to be generated and directed from the first transducer to the second transducer through the bone tissue to obtain a bone-oriented output (received) signal. The bone-oriented output signal is then digitized using the A/D card 28 and processed to obtain an estimate of at least one of parameter net time delay and parameter mean time duration. The net time delay (NTD) and mean time duration (MTD) parameters are defined through use of a set of signal moments M0, M1, and M2. It should be understood that these moments are computed over the first half cycle of the signal. The first half cycle is identified automatically according to an algorithm (program) stored within the computer means 20. The algorithm first computes noise statistics, i.e., the mean (μn) and standard deviation (σn) of the noise-only portion of the received bone-oriented output signal, using standard statistical techniques (see for example the book Statistics Manual by Crow, Davis and Maxfield, published by Dover Publications, Inc., New York, in 1960, and which is incorporated by reference hereinto); this noise-only portion occurs at the earliest times of the received signal, that is before the ultrasound signal propagating through the bony member has reached the receiving (second) transducer. Once the noise statistics are evaluated, the initial time point, ti, of the first half cycle of the bone-oriented output signal is identified. With additional reference to
In the presently preferred embodiment of the invention, the bone mineral density (BMD) of the bone in the bony member is evaluated with further processing according to a linear regression between NTD and BMD, i.e., BMD=a�NTD+b. The values a and b in the linear regression are evaluated by a method of least squares, and using independently measured values of BMD; in the presently preferred embodiment, the independent measure of BMD is obtained with a dual energy x-ray absorptiometer (PIXI, GE Medical Systems, Madison, Wis.). It should however be understood that an estimate of BMD may be obtained not only using NTD, but may include MTD as well.
A fracture risk associated with the living person is computed by a feedforward neural network whose inputs are the ultrasound parameters NTD and MTD, and the associated parameters age, sex, weight, height, degree of bone turnover, and history of fracture. The output of the neural network is the probability of a future fracture, a number between 0 and 1. Neural network is an information processing device that utilizes a large number of simple modules which are highly interconnected with one another. Neural networks are well known in the art (the reference can be made to Neural Networks, A Comprehensive Foundation, by Simon Haykin, IEEE Press, Macmillan College Publishing Company, New York, 1994). They are appreciated for their remarkable ability to derive meaning from complicated or imprecise data and are usually used to trace trends that are too complex to be noticed by either humans or other computer techniques.
It should be understood that a multivariate linear regression, a multivariate nonlinear regression, or even a statistical hypothesis testing algorithm may be used to estimate bone mineral density using at least one of the ultrasound parameters, NTD and MTD. Furthermore, the computation of one or more of said quantities BMD, bone strength, bone fracture risk, bone architecture and bone quality may be derived using at least one parameter as may be derived from the acoustic bone transfer function (in either the frequency and time-domains, or in both), and may also include at least one of said parameter net time delay and parameter mean time duration, and may further include a set of other parameters related to the living being, namely, thickness of the bony member, age, sex, height, weight, history of fracture, cigarette smoking history, degree of bone turnover, and family history of fracture. It should be understood that the degree of bone turnover can be measured in a number of ways, including but not limited to blood analysis and urine analysis. Note also that the nonlinear regression may be implemented with a neural network.
It is useful to provide some additional background as to the relationship between NTD and bone-mineral density. (Again, this density is in fact an areal density—not a true volumetric density—and is also therefore equivalent to total bone mass or overall bone thickness.) For this it is useful to model the bony member as consisting solely of two layers, one bone layer of thickness db1, and another soft tissue layer of thickness ds1; the thickness, d, where d=db1+ds1, is equal to the overall thickness of the bony member. It should be understood that the soft tissue layer includes not only the overlying soft tissues but all the soft tissues located in the path of an ultrasound wave, for example, including the soft tissues within the marrow spaces of any trabecular bone that may be part of the bony member. It should further be understood that the bone tissue layer includes all of the bone located in the path of an ultrasound wave, and that it has been effectively compressed into a single layer. In this model, then, the time delay of the bone-oriented signal is τb, where τb=τb1+τs1, and τb1 is the time for propagation through the pure bone layer, and τs1 is the time for propagation through the pure soft tissue layer. The expression can then be written, using τb1=db1/vb1, and τs1=ds1/vs1, where vb1 and vs1 are the speed of propagation of ultrasound through bone and soft tissue, respectively, as d/vs1−τb=db1 (vb1−vs1)/(vb1�vs1). In this expression, db1 is the parameter of interest, namely (directly proportional to) the total bone mass or bone-mineral density (BMD) of the bony member and the other parameters, namely vb1 and vs1 can, as the present inventors have discovered, be treated as constants. Therefore, recognizing that d/vs1−τb is the net time delay, it should then be appreciated that NTD is proportional to the BMD. It should be also understood that although this model is, strictly speaking, applicable only to a "two layer system," the inventors have discovered that it works well in bony members comprised mostly of cortical bone and even in bony members that have mostly trabecular bone, and in bony members which have substantial amounts of both kinds of bone tissue. Finally, it is important to point out that although the NTD was computed using a time delay of a bone-oriented signal and the bony member thickness, it is possible to use any two (2) of three (3) ultrasound parameters to estimate BMD and obtain similar results as with NTD based on time delay and thickness, the three parameters being (1) time delay, τb, of the bone-oriented signal; (2) the thickness, d, of the bony member (assumed equivalent to the distance separating the two transducers); and (3) the velocity, v (=d/τb), of the signal through the bony member. In addition then, to the relationship between NTD and BMD, it may be understood that BMD is proportional also to tau�(a1−b1�v) and also d�(a1/v−b1), where a1, a2, b1, and b2 are constant regression coefficients, and thus should be considered to be equivalent to the net time delay parameter. It should also be understood that while in the presently preferred embodiments of the invention the time delay of the bone-oriented signal is computed with the method of moments, other approaches could be used in estimating NTD. These methods could include, but not be limited to selection of the time delay based on when the signal first rises above the noise level, or the time when the signal first reaches 5 percent of its maximum value. Thus the present invention should be understood to include any methods which can estimate a time delay of the bone-oriented signal.
However, the presently preferred method for determining the time delay based on moments has been discovered to be remarkably resistant to the effects of noise. Further, it should be appreciated that the evaluation of velocity, v, is best achieved through use of a method of moments as well, using the expression v=d/τb, where τb is computed based on the method of moments, as in the presently preferred embodiment of the invention, although other methods for measuring time delay (and hence velocity) can be used as well, as described in the material hereinabove. It should further be appreciated that although the moments in the presently preferred embodiment rely on the square of the signal in their computation, the present inventors have found that other exponents have proven to have good performance also, for example just the signal itself (exponent=1), and thus all exponents should be considered to be within the scope of the invention. Further, it should be appreciated that the use of most of the first cycle (through the integration of the signal with respect to the various powers of time, t) is a key aspect of the present invention as it is responsible for the superior performance obtained, and therefore the use of the majority of the first cycle in determining time delay of the signal is to be understood to be a major feature of the invention. This would also be understood to include curve fitting a model of the signal to obtain a value for the time delay, as well as various weighting functions and also to include any nonlinear functions as well.
The invention pertains to the non-invasive ultrasound assessment of bone, including the assessment of bone strength, density, architecture, quality, and fracture risk. Since ultrasound propagation through bone depends on both mass (BMD) and architecture (as well as material properties per se), it is useful to combine multiple ultrasound measurements in order to uniquely identify bone properties. In an alternative embodiment of the invention, ultrasound measurements are made from at least two (2) directions, and the information combined in order to more accurately identify bone properties. In an alternative embodiment, ultrasound is propagated in the phalanges (fingers) from 2 directions approximately orthogonal to one another. Then two (2) sets of data, namely two (2) net time duration parameters and two (2) mean time duration parameters are measured and combined in a multivariate regression to output the bone mineral density and architecture of the finger bone. It should be understood than a variety of ultrasound parameters may be used in addition to the NTD and MTD parameters, such as parameters associated with a set of at least two (2) acoustic transfer functions associated respectively with at least two (2) directions of propagation through the bone, as well as the set of at least two (2) bony member thicknesses associated, respectively, with the at least two (2) directions of propagation through the bone, as well as a set of other parameters related to the living being, namely, age, sex, height, weight, history of fracture, cigarette smoking history, degree of bone turnover, and family history of fracture. It should be further understood that this alternative embodiment of the invention may be used on any bone within a living body in which multi-directional ultrasound measurements can be obtained, not just the phalanges, and further that the multidirectional measurements need not necessarily be in directions that are approximately orthogonal with one another, but may also be oblique as well.
There are, however, many bones for which such multidirectional data cannot be obtained. In these cases, another embodiment is preferred. In this alternative embodiment, ultrasound measurements are acquired from a single direction; however the measurements are carried out at 2 sharply distinct frequencies. In a present embodiment, a single transducer acting as a source emits two signals, one signal with a center frequency of 100 kHz, and the other signal with a center frequency of 2.1 MHz. A receiving transducer, also capable of receiving both signals, namely a broadband receiver having a bandwidth of 50 KHz-2.1 MHz measures the two signals and evaluation of a pair of quantitative data is obtained. In a present embodiment, the pair of data is the NTD and MTD, each measured using the said two distinct frequency input signals, respectively. The multi-frequency data serves as an alternative to the multidirectional data, and also leads to improved accuracy in estimating the aforesaid bone related properties.
It should be understood that any quantitative ultrasound parameters (e.g., NTD, MTD, velocity, etc.) can be measured using one of the above embodiments, that is, in a multidirectional embodiment, or a multi-frequency embodiment. It should also be understood that a number of ways can be utilized to generate multidirectional data and multi-frequency data, including the same transducer pair and rotating them (e.g., 90 degrees) to obtain the multidirectional data set, or two different pairs of transducers, arranged or configured to operate in two orthogonal directions (or any oblique direction), multi-frequency transducer pair, or different transducer pairs operating at distinct frequencies, for example. Any means for generating multi-frequency or multidirectional ultrasound data should be considered to be within the scope of the present invention. Also, the preferred frequency differential should be substantial, not less than at least 50%, but 100% or more is preferable. In the previously described multi-frequency embodiment, the differential is 100%�(2100 kHz-100 kHz)/100 kHz=2000%. Further, the multidirectional data should be understood to also include the use of arrays, which allows for oblique propagation between the two transducers. It should also be appreciated that only one of the two transducers may be an array, with the other being a single element.
As yet further advances over the prior art, in yet an alternative embodiment of the invention, concentric or annular phased arrays are used. Either the transmitter, receiver, or both, may be an annular phased array; if only one is an annular array, then it is to be understood that the other transducer is a single element transducer. The annular array is operated to focus into a given region the ultrasound beam; thus a number of bone properties may be determined, corresponding to the spatial regions which are ultrasonically interrogated. Because of the heterogeneity of bone, knowledge of the bone properties (or equivalently, the ultrasound parameters) in the scanned regions leads to an overall much more accurate estimate of overall bone density, architecture, strength, quality and/or fracture risk. The prior art has relied on rectangular 2D arrays, which lead to very expensive systems (due to both high cost of 2D arrays and the large number of source excitation elements required). The annular array overcomes these shortcomings and is well described in Chapter 10 of the excellent reference Medical Imaging Systems by Albert Macovski, published by Prentice-Hall, Inc. in Englewood Cliffs, N.J., in 1983, and which is incorporated by reference hereinto. The annular array can be phased so that cylindrical "slices" of the bone can be scanned, using dynamic focusing, and thus is far superior to prior methods.
Another useful embodiment relies on a phase insensitive transducer receiver to measure the received waveform after it has been transmitted through a bony member. The phase insensitive nature of the receiver allows attenuation dependent measurements to be made much more accurately as compared to the phase sensitive transducers normally used. A number of different ways are available by which phase insensitive measurements can be obtained, using specialized single element transducers, or array transducers using absolute amplitudes and summing together the voltages from each of the elements of the array. It should be understood that the invention includes any way by which phase insensitive measurements may be obtained, and the use of any of a number of ultrasound parameters that may be obtained from the phase insensitive receiver measurements.
In yet one further embodiment of an invention to assess bone, a single transducer 16 is used in reflection mode. In this embodiment, and as shown in
An additional embodiment of the invention is to operate a pair of transducers in both through transmission and pulse-echo mode; in this way, two sets of ultrasound parameters may be obtained, namely that set associated with the transmission measurements, and that set associated with the reflection measurements. It should be understood that these data sets may be further processed, using linear or nonlinear, univariate or multivariate regressions, to obtain one or more of the aforementioned bone properties.
A further alternative embodiment of the invention is shown in
An overall schematic diagram is shown in
The key features of the device (besides its near real-time nature) are: (i) portability; (ii) handheld; (iii) battery-powered; and (iv) a display that provides feedback for the operator. Capability for entering a subject's age, sex, height, weight, degree of bone turnover, and other patient specific factors are also included. The device may also be connected to a computer, a "Palm Pilot," or a printer, or any combination of the above; this connection may be wired or wireless (e.g., Bluetooth). The device in a present embodiment also has a touch screen, to allow convenient control of certain aspects of its operation. One way the device may be used is to display to the operator the received waveform; when the waveform has a given shape, the operator pushes a button on the device which initiates an averaging and data storage operation. This can also be done automatically, without user intervention. As another way of using the device, the operator moves the device slowly over the skin, acquiring a range of parameter values associated with the specific anatomical site being measured. The device processes this set or sets of parameter values in order to obtain an optimal and reproducible estimate of bone strength, density, architecture, quality, and fracture risk. For example, the device may use a maximum likelihood estimate based on the probability distribution (histogram) associated with a given parameter. It should be understood that in order to maximize the utility of the device that the display may have the option of being able to rotate. In one such embodiment (
It should be appreciated that the invention may include the use of a template for improving the reproducibility of the measurement. Although the region to be measured is located generally without the help of a template, the template can be also used after the ultrasound measurement to make a record of the location used for a given subject. This information is then used the next time the subject is measured; the template is used to mark the skin where the measurement was carried out previously, allowing for example, treatment to be monitored since the same site is measured each time. It should be understood that the template approach can be used on a variety of anatomical sites, including but not limited to the heel. The use of a template is important because of the large amount of heterogeneity of the bones comprising a living body. It should be further understood that a variety of templates and locating devices could be devised and used in the manner as described in this paragraph to reproducibly locate and measure a specific region of interest.
In another embodiment of the invention, transducers 16 and 18 in
This alternative embodiment with an array or with two arrays allows a predetermined anatomical landmark to be reliably located automatically through the use of signal/image processing rather than by physically repositioning the transducers 16 and 18 relative to the anatomical region. The anatomical landmark can, for example, be the edge of a heel bone. Locating such a landmark can be accomplished because the parameters disclosed in the present invention are strongly dependent on the type of tissue (e.g., soft tissue vs. bone) through which the ultrasound signal is propagated. For example, the net time delay is much lower (close to zero) when the ultrasound signal travels through the soft tissue laterally surrounding the bone as compared to the bone itself (typically 1-5 microseconds). By locating anatomical landmarks in this fashion, that is through acquisition of an image rather than a single number, improved reproducibility and precision in ultrasound parameter estimates can be accomplished. In one preferred embodiment, data obtained through the ultrasonic interrogation of the tissue—for example through identification of a region of minimal bone density—can itself be used as local reference sites for reproducibly positioning the tissue relative to the transducers 16 and 18. The above embodiments utilizing "electronic" positioning can be implemented using suitable template matching and correlative techniques, as well as edge detection algorithms, well known in the art and as described in the book Digital Image Processing, by Gonzales and Wintz, 2d ed. (1981), Addison-Wesley, Redding, Mass. which is fully incorporated hereinto by reference. It should be understood that all of the techniques disclosed herein including but not limited to linear and nonlinear uni- and multivariate regressions, neural networks, pattern recognition, statistical hypothesis testing, pulse echo and through transmission ultrasound techniques (including but not limited to multi-directional and multifrequency methods), and all of the parameters disclosed herein, including, but not limited to mean time duration, net time delay, velocity, attenuation, acoustic transfer function, acoustic impedance, and bony member thickness, are directly applicable and useful and preferred for use with multi-element, two-dimensional array transducers.
The utilization of multi-element, two-dimensional array transducers 16 and 18, also allows the averaging of a large set of data from a plurality of excitation signals which can lead to more accurate estimates of bone density, strength, and fracture risk, and also improve the capacity for reliable intra-patient and inter-patient comparisons. Furthermore, each element of each transducer 16, 18 can be operated in pulse-echo mode, enabling the soft tissue thicknesses overlying a bone to be measured, and the acoustic impedance and BMD to be estimated—at a multiplicity of spatial locations—as well. For this purpose an ultrasonic pulser-receiver card can be added to the computer 20. The pulser-receiver card can be suitably a Matec Instruments, Inc., of Northborough, Mass., Model No. SR-9000.
In an alternative embodiment, the multi-element, two-dimensional array transducers 16 and 18 can be utilized in a synthetic array aperture mode. In this mode a single excitation signal is passed through a plurality of the array elements, also known as the aperture. By moving the entire aperture one element at a time across the array, high resolution images are made possible, but a high signal to noise ratio can also still be maintained and beam divergence reduced. For this embodiment, the switching networks 27 a and 27 b may suitably be a relay-based system, for example Model No. JX/256 manufactured by Cytec Corp. of Penfield, N.Y. Additional information which may be useful in this approach is Synthetic Aperture Radar, by Curlander and McDonough, John Wiley, 1991, the entire disclosure of which is incorporated herein by reference.
In yet another alternative embodiment, only one of transducers 16, 18 is an array transducer—preferably transducer 18. In this single-array transducer embodiment, transducer 16 may be a 1 MHZ nominal frequency 1.5 inch diameter transducer, Model No. 392, from Panametrics, Inc. of Waltham, Mass. while transducer 18 may be a 850 kHz nominal center frequency, 3 cm�4 cm rectangular array transducer having 128, 3 mm�3 mm elements from Acoustic Imaging of Phoenix, Ariz. In general, transducer 16 should be large enough to cover a region which is of clinical interest and which may also include some anatomical landmarks to be used in repositioning transducer 16. Transducer 18 should be approximately the same size as transducer 16, although the size and shape of the transducers relative to each other may vary. Nevertheless, transducers 16 and 18 should overlap in a region sufficiently large to obtain enhanced reproducibility and accuracy. With respect to a heel region, such a region may be several centimeters in size. However, other anatomical sites, such as a finger, may utilize a smaller region of overlap. Finally, because transducer 16 is a single-element transducer, switcher 27 a is not required in the single-array transducer embodiment.
The single-array transducer embodiment is much easier to implement and is much less expensive than the dual-array embodiment described hereinabove, yet retains most of the advantages of the dual-array embodiment, in terms of enhanced reproducibility and accuracy, as compared to embodiments employing a pair of single-element transducers. It should be understood that the single-array transducer embodiment, like the dual-array transducer embodiment, can be used with a variety of signal processing techniques, including mean time duration and net time delay. It should also be understood that, depending on the signal processing technique utilized, the single-array transducer embodiment may or may not include means for, or the step of, directing the ultrasound signal through a known medium to obtain a reference electrical output signal.
It should be appreciated that while this invention applies to bony members generally in a living being, certain bones which have shown to be well suited for ultrasound examination have been identified. They include, for example, the calcaneus (the heel bone), the phalanges (finger bones), the radius (wrist), and any of the long bones for cortical bone assessment (for example, the tibia and femur, particularly the proximal femur or hip).
In one additional embodiment of the invention, and with additional reference to
In an alternative and presently preferred embodiment of the invention, with additional reference to
In an alternative embodiment of the invention, the set of bony-member output signals is used to obtain an estimate of a width of a bone. In the presently preferred alternative embodiment, the width of a radius in a forearm (i.e., a bony member) is estimated by analyzing amplitude of the soft tissue ("water-wave") component of the received ultrasound signal, and locating the element where the water-wave amplitude is reduced to 30% of its peak value (peak with respect to all the elements). This located ("edge") element determines the location of an edge of the radius. The set of time delays associated with the direct wave are then processed to locate the center of the radius (i.e., the center of the radius is located at the position of the receiver ("central") element having the largest amplitude for the direct wave component). Radius size is then obtained as twice the distance from the edge element to the center element. It should be appreciated that bone size or width can be estimated using a variety of techniques and processing methods and should all be considered to be within the scope of this invention. For example, bone width could be obtained using a mechanically scanned transducer or pair of transducers (i.e., with or without an array transducer). It should be understood that bone width can also be estimated by determining the outside edges on both sides of the bone.
In the presently preferred embodiment of the invention, the bone mineral density (BMD) of the bone in the bony member is evaluated according to a regression between BMD on the one hand, and NTDa and NTDb on the other. This regression is given by BMD=a NTDa�NTDa+b NTDa�NTDb+c, where a, b and c are regression coefficients obtained by the method of least squares. It should be understood that a similar equation can be used to estimate the cross-sectional area, but with different regression coefficients. In addition, an estimate of cortical thickness (CT) may be estimated by CT=e NTDa+f, where e and f are regression coefficients obtained by the method of least squares. It should further be appreciated that the size of the medullar canal (medullar thickness or MT) may be estimated by MT=g NTDb+h, where g and h are regression coefficients obtained by the method of least squares. It should be appreciated that any kind of processing of either the set of three time delays or a set of two associated net time delays should be considered to be within the scope of the present invention. For example, it may be useful in certain embodiments to use a ratio of two net time delays in estimating bone mass, geometry, strength, and/or fracture risk. In other cases, it may be preferred to use other nonlinear (or even linear) combinations of two net time delays or of the three time delays. It should also be appreciated that the measured time delays or the net time delays can be used to estimate not only bone mass and bone density but also to evaluate geometric aspects of the bone, as well as bone strength, bone quality and fracture risk. This can be done with any of the methods disclosed herein.
It should be further understood that although in the presently preferred embodiment an array transducer is used to obtain the set of bony member output signals and the associated set of three time delays, other embodiments are possible and should be considered to be within the scope of the present invention. For example, two single element transducers can be utilized in through transmission mode and mechanically scanned over the bony member to obtain a set of bony member output signals. This mechanical scanning can be achieved for example, by moving the transducers in a coupling bath within plastic containers on both sides of the bony member. Alternatively, only one of the transducers may be scanned while the other may be fixed in space. Finally, although in the presently preferred embodiment, a large single element rectangular source transducer is utilized with a large rectangular linear array receiver, other arrangements should be considered to be within the scope of the present invention. These will include but not be limited to any combination of 1D or 2D or single element transducers operating in through transmission mode that allow measurement of three signals that have propagated through the three pathways in the bony member described supra. In this regard, the transducers may be focused or unfocussed, and phased or not phased, in any combination of features. This should be considered to also include a pair of single element transducers neither of which move ("fixed"), that can in also be used to estimate the set of three time delays and a pair of net time delays associated with a bony member. In this alternative embodiment utilizing a fixed transducer pair, the three time delays are obtained from a single received bone-oriented signal.
Therefore it should be understood that the method of the invention is described by:
(a) acoustically coupling a first transducer and a second transducer to nearby skin on opposite sides of said bony member;
(b) generating an ultrasound signal and directing said ultrasound signal from said first transducer to said second transducer through said bony member to obtain at least one bone-oriented output signal;
(c) processing said at least one bone-oriented output signal to obtain at least two net time delays; and
(d) further processing said at least two net time delays, whereby an estimate of said at least one of the quantities, bone-mineral density, bone mass, cortical thickness, cross-sectional area, medullar thickness, bone width, bone geometry, bone strength and bone fracture risk, is obtained.
It should also be noted that although the invention in its presently preferred embodiment has the advantage of not requiring a measurement of the distance separating the transducers, in an alternative embodiment it may be useful to do this (as in a case where a soft-tissue only ("WW") measurement cannot be made). In this alternative embodiment of the invention, the distance, d, is used with a value of the velocity, vs, of ultrasound in soft tissue to estimate the first time delay, τ1, through the equation τ1=d/vs. In this embodiment it is therefore not necessary to measure the set of signals associated with the soft tissue only path in the bony member; in other words, only two time delays need to be estimated directly from the signal, as long as a distance measurement is also obtained. In yet one further embodiment, concurrent measurements of both a soft-tissue or water only component to estimate τ1 and a distance measurement to estimate d are made in order to also obtain (in addition to the two other time delays) an estimate of the soft tissue velocity associated with a specific living being (through the equation vs=d/τ1). The value of this velocity has in some cases been shown to be related to an individual's or living being's risk of fracture.
In yet a further presently preferred embodiment of the invention, ultrasound coupling gel is not used to achieve acoustic coupling between the ultrasound transducers and subject's skin. Instead, a liquid consisting of water, alcohol, and a wetting agent are utilized to ensure acoustic coupling between the transducers and skin. In this presently preferred embodiment, the liquid is sprayed onto the transducers and skin, which has been discovered by the present inventors to provide adequate acoustic coupling. However, this embodiment is much more convenient than gel-based systems. First, there is little if anything to "clean-up;" simply stated, gel is a mess to clean up. This applies to both the transducers and to the subject being measured. Second, the acoustic coupling liquid used in the presently preferred embodiment acts as both an antiseptic and a disinfectant, both required in the normal course of using a medical device. Finally, this embodiment of the invention allows the apparatus and method to be used in more "routine" settings (compared for example, with a medical clinic), such as health fairs and drugstores, as the liquid will dry up on its own leaving virtually no residue. It should be appreciated that a number of combinations of different liquids should be considered to be within the scope of the present invention. In the presently preferred embodiment, the liquid consists of isopropyl alcohol in a concentration in water of 70%, with 3-5 drops of the surfactant Chlorhexidine Gluconate. However, the present invention should be understood to include any combination of water, alcohol, and wetting agent (surfactant) in any concentrations including 0 to 100 percent for each of the three ingredients. Thus in an alternative embodiment, pure water is used. In addition, although in the presently preferred embodiment, the liquid is sprayed onto the transducers and the skin, other methods of application should be considered to be within the scope of the present invention. For example, a dropper may be used to apply the liquid. Alternatively, an electric pump may be used to spray the liquid onto the skin, the transducers, or both. Therefore, the invention should be understood to include any method or apparatus used to apply the liquid to the transducer and/or skin. It should also be understood as well that the liquid may be applied to only one transducer, to skin on only one side of the bony member, or in any combination (e.g., both transducers, skin on both sides of bony member, both transducers and skin on only one side of bony member, or one transducer and skin on both sides of bony member).
In yet one further embodiment of the invention, both ultrasound and x-ray absorptiometry are utilized to assess bone. In a presently preferred embodiment of the invention, ultrasound and x-ray densitometry are used at the forearm as a means for assessing both the bone mass and the degree of bone mineralization. An insight of the present inventors led them to realize that ultrasound and x-rays respond differently to changes in bone mass that result from cortical and trabecular porosities, cortical thicknesses, and bone size on the one hand, with changes in degree of bone mineralization. Therefore, by combining both ultrasound and x-ray measurements, estimates of bone mass and degree of bone mineralization, two important factors in bone strength and fracture risk, can be obtained simultaneously. In a presently preferred embodiment of the invention, a set of two ultrasound net time delays (in microseconds) are combined with a bone mass measurement (made with a General Electric PIXI (DEXA) bone densitometer (bone mineral content in grams) and serves as input to a neural network, whose output is degree of bone mineralization and overall cortical thickness. However, it should be understood that any kind of linear or nonlinear processing may be utilized in evaluating the degree of bone mineralization and cortical thickness (or any mass related feature such as trabecular porosity). It should be further understood that although the x-ray and ultrasound measurements be performed at the same site (in this embodiment the forearm, but any site may be utilized), it is also to be considered to be within the scope of the present invention that distinct sites can also be used (such as the hip for x-rays and the heel for ultrasound). It should also be noted that in this alternative embodiment, only one net time delay may be used in conjunction with an x-ray measurement.
It should also be understood that the methods and apparatus disclosed herein can be used to estimate one or more of the said bone quantities, namely, bone mass, bone density, geometry, medullar thickness, cortical thickness, cross-sectional area, bone width, bone size, bone quality, bone strength, and fracture risk and not only of the bony member being ultrasonically interrogated, but also at a site anatomically remote to that site, for example, the hip and spine.
While several embodiments of the present invention have been disclosed hereinabove, it is to be understood that these embodiments are given by example only and not in a limiting sense. Those skilled in the art may make various modifications and additions to the preferred embodiments chosen to illustrate the invention without departing from the spirit and scope of the present contribution to the art. Accordingly, it is to be realized that the patent protection sought and to be afforded hereby shall be deemed to extend to the subject matter claimed and all equivalence thereof fairly within the scope of the invention.
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|Citing Patent
|Filing date
|Publication date
|Mar 22, 2010
|Oct 23, 2012
|Transense Technologies Plc
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|Victor Alexandrovich Kalinin
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|U.S. Classification
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|International Classification
|Cooperative Classification
|European Classification
|Feb 7, 2008
Owner name: CYBERLOGIC, INC., NEW YORK
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Owner name: CYBERLOGIC, INC., NEW YORK
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:LUO, GANGMING;KAUFMAN, JONATHAN J.;SIGNING DATES FROM 20080131 TO 20080202;REEL/FRAME:020479/0488
|Jun 2, 2014
|Fee payment
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text:
Encourage Weekend Retreat
On April 29-30, 2016 at Spring Lake Camp and Retreat Center our first ever women's retreat was held at Spring Lake! It was wonderful and amazing!! We are sharing some of our photos from the glorious weekend. In spite of the rain, the Holy Spirit moved among us and blessed our obedience!
Meet Our Speakers
|Meet Our Speakers
|Who They Are
|Vickie Petz Henderson, M.D.
|Vickie practiced obstetrics and gynecology for twenty years until her active life was derailed by a rare neuromuscular disease. With a unique perspective as a physician, patient and lover of God and His word, she offers encouragement for those whose lives have been turned upside down. You can learn more about her journey from her blog, My Upside Right Life.
|Katie Clifton
|Katie is a lover of Jesus, her husband, and her four children. Katie serves ReNew Church of Benton, Arkansas alongside her husband who serves as Pastor. Katie's passions include reaching the people of Kenya through the African Christian Outreach Organization and advocating for orphans through adoption. She enjoys writing and encouraging women on their walk with the Savior. You can read more from Katie on her blog Mire and Manna.
|Carissa Hardage, LMSW
|Carissa is a Licensed Masters of Social Work, who worked as a Clinician in outpatient child and family therapy. She is currently working towards a graduate degree in Biblical and Theological Studies through Dallas Theological Seminary and serves her family as an at home wife and mom to her three children. She has a heart for encouraging women and for discipleship through the study and teaching of God's Word. Carissa has served as Editor of My Journey of Faith Magazine since it's launch in May of 2012 and loves to share her journey on her personal blog, Faith and the Fig Tree.
|Karen Jordan
|Karen encourages others to tell the stories that matter most as an author, speaker, writing instructor, and blogger, focusing on topics about her faith, family, and writing. Karen and her husband, Dan, live in Hot Springs Village, Arkansas, near their two children and seven grandchildren. Read Karen's blog at www.karenjordan.net
|Miranda Lytle
|Miranda is a graduate of Ouachita Baptist University and the University of Central Arkansas graduate school program. She currently works as a Clinical Dietitian at Baptist Health Hospital in Little Rock, Arkansas. Miranda has a heart for reaching others for Christ in her community.
|Terri Lytle
|Terri is wife of Steve and mother of four children. She works as a registered nurse in Surgical Services in Allen, Texas. She has a passion for studying God's Word and helping people pursue a more intimate walk with Him.
|Carla Covert
|Carla lives in Benton, Arkansas with her husband of 18 years and their two boys, ages 14 and 10. Carla is a believer in the grace of Jesus Christ and gives him credit for taking her ordinary, sometimes messy, life and making it extraordinary for His glory. Because of His amazing grace, Carla has a heart for sharing her story to encourage others.
|Andrea Lennon
|Andrea lives in Conway, Arkansas, with her husband Jay and two sons. She serves the Lord through a teaching and writing ministry called True Vine Ministry. With transparency and love, Andrea shares the Word of God and challenges women to know deep in their hearts the life- changing truths written in the pages of the Bible. Andrea also serves as a women's ministry specialist for the Arkansas Southern Baptist Convention. To learn more about Andrea and True Vine Ministry, access her website at www.andrealennon.net.
Go See The Gallery!
Choose Retreat 2016!

subset: commoncrawl


text:
Workers "close to burn out" in pursuit of pay rise and promotion
Qualifications not overtime matter most to employers, as UK urged to work smarter not harder.
Eight in 10 Britons are overworked, with almost a third "burnt out" or "very overworked", according to a new survey from The Open University. Employees believe that working longer hours is one of the best ways to earn a promotion or pay rise despite being considered important by just one in ten employers. With just 15% entirely happy with their career, The Open University, the UK's largest academic institution, is urging Britons to make 2015 the year of their career by exploring more effective methods of career progression.
In improving economic conditions, nearly two-thirds of us regularly work overtime, with nearly 10% working at least an extra 40 hours per month; a full working week. However, whilst a quarter of employers said they merited staff who met deadlines and targets, a greater number (46%) cited work-related qualifications gained through additional education, as a reason to offer a pay rise or promotion. Other things viewed favourably by employers were staff who went on training courses and who were eager to learn new job skills.
Helping Britain's workforce to progress and enhance their careers, The Open University is releasing a Guide to Fast-Tracking Your Career containing expert advice from its Careers Advisory Service to help people work smarter, without necessarily working harder. The guide will be an invaluable resource for those who want to take their career to the next level.
Despite further qualifications and training being so highly valued by employers, just 11% of workers recognise the value of doing so. In 2015, the range of options available means that part-time study has never been more flexible and accessible. For many, the skills and knowledge learnt can be put to use in the workplace almost immediately.
Keith Zimmerman, Director, Students at The Open University says:
"The start of a new year is the perfect time to take stock of your career and make decisions to change it for the better. The survey shows that people in the UK work very hard but some overlook the more effective means of achieving career goals."
"For more than 40 years we've seen at the OU how part-time study can impact on careers, whether in terms of offering a boost, or even setting out on a new path entirely. We also hear from employers how our students are able to take the knowledge they have learned on their course and apply it directly in the workplace.
With higher-level skills more important to our national economy than ever, now is the perfect time to think about whether you've got the right ones."
To download the free Guide to Fast-tracking Your Career, visit www.openuniversity.co.uk/guide or for more information on how an Open University qualification could give your career the kick-start it needs call 0300 303 0068.
Careers Advice
Where to begin?
Undecided about what to do next after university? Don't panic GradJobs will help you! It is important to remember that you are not alone – there are many who don't have any idea what to do after graduating.If you are unsure which career is right for you, or simply not sure where to start on your job hunt, then head to the Advice Clinic at the National Graduate...
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You've made it through the first round and you've got an interview! Yet, it's nerve-wracking going into a room and getting grilled to prove how you are the best candidate for the role. To create the right impression and make a positive impact at interview stage, there are a number of things you must take into consideration and prepare for...
Applying for a Job
From the perfect CV to cover letters, online applications, recruitment agencies, psychometric testing, job AND assessment centres, applying for a job can sometimes seem a little daunting, and that's before you've even secured an interview! Follow our step-by-step guides and handy tips from industry professionals to make you stand out from your...
Recruitment Exhibition
How the National Graduate Recruitment Exhibition can aid your job hunt
For many graduates, looking for their first job can be a daunting and unsettling process – not only are you moving away from university and the community that you have built but you are also having to take that first step into the working world...
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Ang krang
Ang Krang, and they pack a bite that you remember. They like to hang around remote temples in the countryside waiting for johnny foreigner to come along and catch him unawares as he soaks in yet another temple discovery. I have many recollections of such attacks during my temple-hunting expeditions across Cambodia. I used to joke with my pals like Sokhom that if the landmines didn't get us, the ang krang would. Black humour, you can't beat it. I spotted these guys and their dance of death on a post near O'Malu waterfall in Koh Kong province yesterday. Yesterday's black humour revolved around ang krang and black leeches, both of which were out and about in abundance.
Labels: Koh Kong


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Rs. 2,300.00
|Black and blue hued woven mesh earrings. These statement stunners are sure to attract attention!
Click here or email us at email@example.com for Returns and Exchange.
Returns or Exchange accepted within 7 days of delivery.
No Returns or Exchange for Bikini, Lingerie & Accessories.
For further details, Kindly Refer to our Shipping & Exchange Policy.


text:
See video below.
The intent of denial is to accommodate the cultural Marxism myth that race is nothing more than a social construct. That allows Marxism to evoke white racism as the cause of economic disparities between races.
In reality the correlation between IQ and income in free markets is indisputable. East Asian households earn more than white households in America because East Asians tend to have higher intellects. Likewise, white households have higher incomes than black households.
The damage caused by IQ disparity denial is made evident in the health care of those with lower intellects. Those individuals are denied access to proper care when health care professionals are compelled to pretend low-intellect people have the same comprehension as high-intellect individuals.
The conservation between Prof. Linda Gottfredson and Stefan Molyneux is essential for those who wish to know the truth about race and intellgence.
Linda Susanne Gottfredson is a professor of educational psychology at the University of Delaware and co-director of the Delaware-Johns Hopkins Project for the Study of Intelligence and Society.
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Margaret Vaughn is the wealthiest heiress in London—or so everybody thinks. Saddled with debts and facing financial and social humiliation, she finds an unlikely savior in Tom Poole . . . After surviving a shipwreck and amassing a fortune in the gold fields of Australia, Tom Poole is the toast of London society. Yet despite his new found fame, he's never forgotten his own humble beginnings. When he learns of Margaret's plight, he offers her financial assistance—but his interest is not strictly business. This rugged adventurer now seeks a different kind of gold. Although many men pursue Margaret's hand because of her beauty and lands, can Tom convince her it's her heart he's after?
Three hours. Three hours it had taken to sort out the mess, to clear the guests from the hall as graciously as she could, and to settle with the owner for the damage. It would take far longer to recover from the blow to her good name. Tom Poole had humiliated her publicly. He had shown the world that he was nothing but an ill-bred, lower-class hooligan with no regard for common decency. He had turned their wedding breakfast into a brawl. Even now, the memory of Tom's face during the fight sent chills down Margaret's spine. Even though she had seen him threaten a man before, she had not fully comprehended how volatile he was. Now that she was his wife, how was she to deal with this darker aspect of his nature? Margaret paced up and down in the suite of rooms Tom had rented for them in the hotel. She felt trapped in these unfamiliar surroundings, but coming here after the wedding breakfast had been her only option. All her clothes and immediate necessities had been brought here.
"Shall I find some tea, madam?" Bessie asked. "Perhaps some chamomile, to help soothe the nerves?" She was sitting in a corner of the room, darning and keeping Margaret company until Tom arrived. Where was Tom, anyway? He'd left with the men carrying Richard out of the hall, and he'd arranged to get the man home and under a doctor's care. Then he had left, saying grimly that he had something else to attend to. But he had not told her what it was. Nor had he offered any apologies.
"Tea won't be necessary," she told Bessie, ignoring her maid's concerned expression. Nothing would calm her until she had given Tom a good piece of her mind. Margaret whirled from the window as the door opened and Tom walked in. Whatever he'd been up to since they had parted, he'd done nothing to repair his disheveled appearance. His cravat was loose, his shirt collar smudged with dirt and blood, his coat sleeve torn. Her heart leaped into her throat when saw dried blood crusted along his right eye and hairline. She told herself it was anger. What kind of a man fought like this, heedless of danger to himself? "Where have you been?" she demanded. Tom shot her a look, but didn't answer. He set down his hat and looked at Bessie.
"Leave us, please. I need to change."
"Then we shall both leave," Margaret countered, motioning for Bessie to follow her to the door. "Where is your valet?" Tom put out a hand to stop her. "My valet has the night off. You will help me."
"Me?" Margaret said, astounded.
"You are my wife."
"Precisely. I am your wife, not your valet."
He took a step toward Margaret, hands outstretched. "I had hoped I could count on my wife to help tend my wounds."
Margaret took an involuntary step back. What did he think she'd do, after the mortification he'd caused her today? Run into his arms? He was a fool if he thought so. Disappointment crossed his face, but he made no move to close the gap. Instead, he surprised Margaret by walking past her, pulling off his coat as he did so and tossing it onto a table. He began tugging furiously at his cravat. Good heavens, he's serious, Margaret thought. He's going to undress right here in front of me. In front of the maid. Bessie flushed, turning her eyes away in embarrassment, and Margaret had to take pity on her. This was Margaret's problem now. She would have to face her husband alone sometime, and the sooner they had things out between them, the better.
"That will be all, Bessie. I will send for you if I need you."
"Yes, madam," Bessie said, with unmistakable relief. She hastened to the door and let herself out.
The cravat came off, and Tom tossed it onto the coat. His shirt fell open, exposing the base of his throat and upper portion of his chest. He slipped the braces off his shoulders. Margaret stood, unable to move, her anger displaced by the shocking novelty of seeing a man undressing. Her heart began to pound wildly, so much so that she thought he must be able to hear it. She tried to hold on to her resentment at all that had happened today, at how his actions had embarrassed and humiliated her. But it was difficult not to be distracted by the outline of his broad chest under the white shirt, at the way his trousers dropped lower on his hips without the braces to hold them up. He looked up and caught her looking at him, and Margaret thought she detected a particular glint in his eye. He had promised her he would wait, but here he was, half-undressed, and today he had proven himself a man of uncontrollable passions. What if he decided to act now, even if she was unwilling? But he made no move to unbutton his trousers. Instead, he dropped into one of the two overstuffed chairs that flanked the fireplace. He lifted one foot and began to tug at his boot. After a moment he seemed to think the better of it and allowed his foot, still shod, to fall back to the floor. He rubbed his hands over his face but then stopped, wincing, as his hands found a tender spot—a cut on his forehead that was probably the result of his tumble into the broken glass. With a groan he leaned back in the chair and closed his eyes.
"God, I'm tired," he said. Sensing that there was no immediate threat to her person, Margaret found her righteous anger returning. She crossed her arms and regarded him coldly.
"I should think you would be tired." Her voice was brittle and hard, as she intended it to be. "It takes a lot of energy to get married and destroy a banquet hall in one day."
If you could visit a time and place in the past, where would it be, and why?
About the Author
Jennifer Delamere writes romance and adventure set against the backdrop of real events in Victorian England. Her debut novel "An Heiress at Heart" was a finalist for the Romance Writers of America 2013 RITA® award—the highest award for romance fiction. Her second novel, "A Lady Most Lovely," earned a starred review from Publishers Weekly. Jennifer earned her B.A. in English from McGill University in Montreal, Canada, where she also gained fluency in French and developed an abiding passion for winter sports. She's been an editor of educational materials for over a decade. An avid reader of both classic novels and historical fiction, she also enjoys biographies and histories, which she mines for the vivid details to bring to life the characters and places in her books.


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14 results for
Biking Hydration Packs
4.9 out of 5 stars.515
4.9 out of 5 stars.57
4 out of 5 stars.54
4 out of 5 stars.51
3 out of 5 stars.51
Comfortable and works wellThis reviewer rated product 5 out of 5 stars.NoSpursCowboy4 months ago
I bought this pack several months ago, but only really put it to the test this past weekend on an 11 mile bike ride in the Texas heat. The water stayed cold in the bladder, only the first sip would be warm as there is no insulation on the tube. Straps were comfortable even though i was hunched over on an old style 10-speed. Plenty of room for other gear and the "airflow" back panel is nice too. No issues with quality and I would buy again if needed down the road.
good and badThis reviewer rated product 4 out of 5 stars.dont have one1 month ago
Just try to find a new bladder for it. Have looked every where. Even though I like the pack would never buy because they do not have replacement bladders.
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Love itThis reviewer rated product 5 out of 5 stars.Thicvik6 months ago
I bought this hydration pack for my daily 3 to 4 mile walk a day, I live in South Carolina so it's really HOT here. I love this, it fit perfect and it is so convenient, has pockets to hold my cell phone and keys if needed. Its better than wearing my fanny pack with a 20oz water bottle which was slowing me down.
Great valueThis reviewer rated product 5 out of 5 stars.knightmom1 year ago
We bought these to go hiking in Canada and they worked fabulously! Very good product with a low price.
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Easy to fill & sealThis reviewer rated product 5 out of 5 stars.gabboca1 month ago
I've used the Antidote reservoirs for several years. I find this reservoir easier to fill with the new handle and much easier to get a good seal by screwing down the top. I wish they had left the drying arms from the old model.
10 state Harley ride with this excellent reservoirThis reviewer rated product 5 out of 5 stars.Kïdd344 months ago
Not sure why all of the neg reviews on cleaning and use but this thing is very easy to dry out and works perfectly at 80 mph on a Harley you have to be smarter than the reservoir Yes hose when it's hot out gets very pliable but what product wouldn't just have to be smarter than the hose To clean 2 paper towels empty out the water then wipe out u can get around the hose attachment area and then once again for a almost complete dried out reservoir I then took a spaghetti spoon and stuck it ... inside to keep the reservoir open woke up the next morning and it was dried out Other than that most of you are on two feet I was on my Harley 10 states mostly 80 mph and it was flawless I truly don't see myself needing to purchase a new one everThis review was originally posted to camelbak.com.
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Good Product Worried About MoldThis reviewer rated product 4 out of 5 stars.TrevDukeHogs4 months ago
Good product took it fishing and it was very helpful. It is hard to clean out and dry so I put it in the freezer to prevent mold.
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water pack started leakingThis reviewer rated product 3 out of 5 stars.IH291 year ago
My son likes the pack in general but the water pack started leaking at the seam on his second bike ride so we will take it back to the store.
- Read more about this product


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"Arm appointment & experience"
About: Glasgow Royal Infirmary / Accident & Emergency Glasgow Royal Infirmary Accident & Emergency G4 0SF Scottish Ambulance Service / Emergency Ambulance Scottish Ambulance Service Emergency Ambulance EH12 9EB
Posted by Driveway (as ),
Dear Sir/Madam,
Just a wee note that I felt it was poor from NHS - the Royal - where they said to me as I left my arm examination 3 weeks ago 'oh, we'll send it out' at reception but didn't, I have just called & its tomorrow.
Wouldn't criticize usually - often no need - but ought to have not just fobbed me off, lucky we can still make it however.
The appointment may even have been sent but maybe not delivered by Royal Mail so best to address at the time.
However I feel the ambulance staff that came to pick me up at home were brilliant & as regards the A&E, while it took a few hours to get plastered (others more important than me), I was well looked after and the ambulance prompt, the Saturday before Christmas.
Kind regards
Response from Lorna Gray, Patient Experience, Public Involvement Project Manager, NHS Greater Glasgow and Clyde 2 years ago
Thank you very much for taking the time to highlight the issues you have had with communication around your appointment. I can completely understand your frustration at this, particularly as this could have resulted in you missing your follow up appointment.
I would like to send your comments on to the relevant service to find out how they organise their follow up appointments and so I can pass on your experience. To help me do this, could you just confirm for me what clinic you were attending and I can makre sure your valuable comments go to the right people. Please feel free to comment here or get in touch with me directly at firstname.lastname@example.com.
Many thanks,
- {{helpful}} {{helpful == 1 ? "person thinks" : "people think"}} this response is helpful
- Was this response helpful? Yes
Thank you for your feedback.
See more responses from Lorna Gray


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The luxury coupe market has not always been Audi's bag. Most associate the German mark with solid, reliable sports sedan. But as competitors expand their model lineup to fit what seems like every possible niche, Audi has increasingly begun to keep pace with the launch of several two-door models - not least as Audi S5.Read More »
Home / Tag Archives: 2009 Audi S5


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IBM WebSphere Message Queue (MQ) Create Queue Manager Project
An IBM project to create Queue Manager on existing IBM MQ on a target server
Project overview.
Here is a summary of what this project will achieve.
This project is designed to create Queue Manager on existing installation of IBM WebSpehere Message Queue using RapidDeploy.
The server in the project is Windows. It can be cloned to Linux if required.
The project is preconfigured with one target environment.
Specific application configuration items can be changed between environments, by use of Data Dictionary items.
On MidVision documentation you can find more information and step by step tutorial how to create this project.
- A remote Windows server with firewall configuration that allow connection from the machine when RapidDeploy instance is installed (for testing purposes we suggest to turn the firewall off).
- RapidDeploy Agent should be downloaded and running on a remote Windows server
- You should have IBM MQ already installed on your remote server (follow this tutorial to install IBM MQ)
- IBM MQ installation is based on tasks that are included in rapiddeploy-core-plugins-prd-ibm-wmq.jar, rapiddeploy-ext-wmq-jar-3.5.18.jar - so make sure these jars are in your RapidDeploy agent lib folder or they are added to your project classpath
- Make sure you have correct values in your hosts file (http://www.rackspace.com/knowledge_center/article/how-do-i-modify-my-hosts-file).
What is preconfigured and demonstrated
- One target server for Windows. The user will need to configure the actual hostname for this logical server definition.
- Use of the RapidDeploy agent. If deploying to Linux then you'll probably want to change this to use the SSH.
- WmqDefaultManageQueueManagerTask task to create Queue Manager on your IBM MQ (see the task specification)
How to use this project.
- Download the project to your desktop by clicking on one of the links. The file will be saved as IBM_MQ_CREATE_QM.zip
- Log into your RapidDeploy instance as mvadmin.
- Navigate to Resources-> Projects.
- In the top right hand corner click on the Upload Project button.
- Select the zip file you downloaded in step 1.
- You are guided through a project import wizard. The important thing to check and change (if necessary) here is the path to the project storage directory (you will need to check it in SCM Repository tab, Artifact Repository tab and File System tab). Look at the example below:
For example you are running RapidDeploy on Windows and your MV_HOME is set to C:/MV_HOME/midvision. Usually all RapidDeploy projects are stored in the MV_HOME\projects directory. After importing our project, if you noticed that Project Root Directory path on the SCM Repository tab is /rd/projects/IBM_MQ_CREATE_QM, then in this case you will need to change the path to C:\mv_home\midvision\projects\IBM_MQ_CREATE_QM as it is shown here:Change paths in Artifact Repository and File System in similar way
Once the project is imported, there are a couple of things you'll need to do.
Firstly, you will need to change the server configuration. In order to do that navigate to Resources -> Targets -> Servers and find aws-wmq-windows-server (this is the name we used in our sample project). Edit this server - put correct Hostname then navigate to Transport tab and check if it is possible to connect to your remote Windows server by clicking Test connection .
Note that Successful connection is mandatory to go further!
- Secondly, navigate to Resources -> Projects and edit the project. Navigate to the Packages tab and click the Create Package button. A new package is created with a version number. This is the package you'll deploy later, containing all the environment definitions, actions and payload ( IBM_MQ_CREATE_QM-0.0.1.jar ) to allow the jobs to be run on all defined servers
- Navigate to Jobs-> New Job.
- Select the project you created earlier. You will see a tree view of server/environment and application.
- Select the one you want to deploy and follow the wizard.
- On the Version panel you select the version (package version) you want to deploy.
- Since there is only one package, it is preselected. The latest package will always be preselected by default.
- Click on the Skip to Finish checkbox and click Next .
- On the final tab click the Start Job button. The deployment is started and you see the tasks executed and job log in real time.


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One spectacular Saturday morning while I was in Akaroa recently I had an Italian biscuit with coffee at the local deli . The biscuit was so delicious with the strong black coffee. Sitting enjoying the coffee and biscuit with one of my closest friends was my idea of a perfect moment. I vowed to find a recipe and make the biscuits myself.
I Googled 'delicious Italian biscuit' and up they popped. 'Bruitti a Buoni' meaning 'ugly but good'. It's a little hard to believe these biscuits only have four ingredients and are super easy to make. You do have to make them the night before eating though, as they need to stay in the oven overnight.
You will need:
- 2 egg whites
- 1/2 cup castor sugar
- 2/3 cup of hazelnuts (I've also used macadamia and walnuts and they both work well)
- 50gm good quality dark chocolate
Start by chopping the nuts and chocolate. You could do this in the processor but I prefer them to be a bit chunky,
You may notice the two different chocolates I have pictured. That is because I used the last of a packet of 70% cocoa and started on the 85% (can't be too organised or the earth could fall of it's axis). Anyway, the darker chocolate works well in this sweet mixture.
Now turn on your oven to 180°C. Put your two egg whites into a clean bowl and beat until stiff. Add your sugar slowly while still beating.
When it is thick and glossy fold in your nuts and chocolate. Put normal biscuit size dollops onto trays lined with baking paper leaving plenty of room between each dollop.
Place in oven and turn the oven off. Leave overnight and voilà or more appropriately ècco.
For your information the biscuits are not blue that's just my photography.
Since writing this recipe I have discovered that by the addition of a tablespoon of flour folded in with the nuts etc you get a more chewy texture.
These are so quick and easy to make with fabulous results. Give them a try and let me know how you go.