text:
Subcutaneous glucose measurement device
A subcutaneous glucose sensor comprising an infrared emitter which transmits light through a narrow sample of interstitial fluid held in a light transparent sample trough. The sensor can be incorporated with an insulin pump in order to create an insulin delivery and feedback measurement loop system.
[0001] The present application claims benefit of copending provisional patent application Ser. No. 60/178,596, filed Jan. 28, 2000, which is incorporated by reference herein.FIELD OF THE INVENTION
[0002] The present invention relates generally to medical sensors, and, more particularly, to glucose sensors for implanting in the human body.BACKGROUND OF THE INVENTION
[0003] Glucose sensing technology is needed in medical applications primarily to monitor the condition of patients with diabetes mellitus. This disease inhibits the body's ability to metabolize glucose. This inability to metabolize glucose can be due to a lack of the hormone insulin, which allows glucose to be transported into somatic cells. The disease may also be due to a defect that causes the insulin produced by the body to be inefficient. The current recommended treatment for this disease involves tight regulation of the patient's diet, monitoring of blood sugar levels, and injection of insulin or ingestion of sugar when needed. Widely fluctuating blood sugar levels may lead to acute damage, diabetic shock, and death in severe cases. More mild fluctuations in blood sugar levels can lead to long term complications such as blindness, loss of circulation and sensation in the extremities heart disease, and kidney failure. In 1994, a combination of these acute and chronic complications made diabetes mellitus the seventh leading cause of death in the United States.
[0004] The current treatment methods for diabetes have improved the average life expectancy for diabetics from less than thirty years of age in 1950 to over fifty years of age today. This last revolution in the treatment of diabetes was due primarily to the production of injectable insulin and the development of blood glucose measurement techniques. Improvements have been made in recent years with the development of implanted insulin pump devices and the knowledge that tight control of blood glucose levels can prevent sixty percent of all long-term complications of diabetes.
[0005] Currently the primary impediment to tight control of blood glucose levels is the state of the art of glucose sensing technology. All currently available glucose-sensing techniques require a sample of blood to be taken, usually from the fingertip. This sampling procedure is painful, inconvenient, and intrusive on the daily life of the patient. Furthermore, people with insulin dependent diabetes have complained that it has become difficult to obtain blood samples to test blood sugar levels after years of pricking their fingers and scar tissue buildup. Consequently, most patients do not measure their blood glucose levels as often as they should in order to prevent long term complications of the disease. Thus, the common glucose monitoring devices require high maintenance.
[0006] According to a study released by the National Institute of Health in 1993, tight glucose control has been predicted to stop sixty percent of all long-term complications of diabetes. The National Center for Disease Control estimates that there are 15.7 million Americans suffering from diabetes mellitus with almost 200,000 deaths related to diabetes in 1998. The annual market for glucose detection technology was estimated at 20 billion dollars. Current research is being performed to develop a better glucose detection system, such as non-invasive, near-infrared sensors and trans-cutaneous chemical sensors.
[0007] An improved means of collecting blood glucose measurements would be desirable to patients, doctors, and insurance companies for several reasons. From a user perspective most diabetic patients would be happy with an improved sensor simply because they would no longer be required to take blood samples several times a day. This factor alone would contribute to an improvement in the quality of life for the patient.
[0008] As taking a blood sugar measurement becomes less obtrusive, the patient would be more likely to take these measurements on a regular basis. This type of regular and frequent measurement has always been the most helpful to physicians in treating diabetes. If used in conjunction with an implanted insulin pump that allows for frequent small injections of insulin, rather that occasional large injections, blood glucose levels could be controlled to close to the normal range. This type of control would improve not only the patient's quality of life, but also their long-term health.
[0009] Because of the long-term health benefits, even a very expensive device that could produce these results should be desirable to insurance companies. A one-time investment of this type would prevent a great deal of expense later in life. However, it is also probable that an implanted glucose-measuring device could be designed that would be less expensive than current glucose measuring techniques. The average diabetic currently pays nearly $4,000 annually in diabetes related health expenses. Roughly, one quarter of that amount is for glucose measuring supplies. The total cost of glucose measuring supplies to the insurance company is higher than one thousand dollars annually. Even a several thousand dollar device would pay for itself in the course of a few years even when long term health benefits are not considered. Due to the cost of blood glucose measurement and the number of diabetics in the United States, the current estimated annual market for an implanted glucose sensor is estimated to be $20 billion in the United States alone. If such a device were sold in a global market the annual market would probably be at least doubled.
[0010] The requirements of an implanted glucose sensor were derived from knowledge of how current glucose meters work (Bayer Corp. 1998) and with a general knowledge of implanted device requirements. In order for an implanted sensor to work as well as current external glucose meters the sensor would optimally have to detect a range of blood glucose levels from less than 40 mg/dl to several hundred mg/dl. There are also several other considerations that have been suggested to be necessary for the ideal sensor to be produced. These factors include, but are not limited to, high sensitivity, low power needs, timely response, little calibration, miniaturizable, easily produced, and long-term usability (Walsh, 1997).
[0011] Several main methodologies have been proposed to date in order to produce a sensor that meets these requirements. Much research has been put into developing a chemical sensor (Armour, 1990; Cough and Armour, 1995; Lemke and Henning, 1990; Leypoldt, 1984; MiniMed, 1997; Peura, 1998; Tse and Couglt, 1987; Walsh, 1997). Most of these chemical methods are dependent on the reaction of glucose with some sort of enzyme to produce an electrically measurable change in ion concentrations. The most common method used in this type of device is the reaction of glucose and oxygen with an enzyme called glucose oxidase. This reaction produces gluconic acid and hydrogen peroxide. Platinum will then remove the hydrogen from the hydrogen peroxide and produce hydrogen gas, oxygen, and two electrons. These electrons create a current that is proportional to the concentration of glucose. The problem with this method is that if the hydrogen peroxide is not broken down and then escapes the device, it would be harmful to the body. In addition, all chemical sensors have the problem of enzyme denaturation. This problem requires frequent calibration of the sensor, and can limit the life span of the sensor greatly.
[0012] Another primary method that is being researched is the use on non-invasive optical detection methods (Heise, 1994; Robinson, Ries et al., 1992). This method relies on looking at the absorption or reflectance spectrum of tissue using electromagnetic radiation in the near infrared region. This wavelength of radiation will penetrate well into the tissue. However, it has not been shown that absorption in this region is particularly selective to glucose. The greatest difficulty has been the complexity of the light-tissue interaction. By using a non-invasive approach, this device is required to look through many different types of tissue. This method has been used successfully in clinical situations, but there is a large amount of error introduced by placing the device improperly on the body. Small changes in tissue orientation and placement have the potential to greatly affect the measured results. In addition, the high-powered light sources and sensitive detectors used are very expensive and difficult to maintain.
[0013] Past research by H. Zeller, P. Novak, and R. Landgraf provided many results that were useful in the choice of glucose sensor method (Zeller et al., 1989). Their research suggested that an infrared sensor would respond directly to the glucose molecule instead of indirectly, like electrochemical methods, and would provide the needed long-term stability required by an implanted device. Thus, Zeller et al. investigated the absorption of glucose in the mid-infrared region from 2.5 &mgr;m to 20 &mgr;m. They discovered that under physiological conditions there were five main glucose absorption peaks: 1040, 1085, 1109, 1160, and 1365 cm1 (9.62, 9.22, 9.02, 8.62, and 7.33 &mgr;m, respectively). This region is often referred to as the "fingerprint region." Various substances were investigated that are related to blood: hemoglobin, albumin, &agr;-&bgr; globulin, &ggr;-globulin, 1 m-urea solution, 2 m-glucose solution, glucose in blood, blood, and plasma. It was shown that the 1040 cm−1 peak is unique to glucose. The 9.22 &mgr;m peak was also found in several substances, but the results suggested that albumin was the only substance to contribute to this absorption in the plasma. The 9.02 &mgr;m peak was found also in hemoglobin. The 1 &mgr;m-urea solution was the only substance to interfere with the 8.62 &mgr;m, but this is likely to cause problems. The 1365 cm−1 peak showed several peaks for various substances. The Zeller et al. research concluded that the best peak to use is the 9.62 &mgr;m, and that the 9.02 &mgr;m and 8.62 &mgr;m peaks are useful if other substances are accounted for.
[0014] There have been several reports of using an implanted optical method of detection in the literature. A company called Sensors for Medicine has been looking for an enzyme that will fluoresce only when bonded to glucose, that would be imbedded on an implanted microchip (Walsh, 1997) There has also been some research done into using the mid-infrared region of the electromagnetic spectrum which has been shown to be sensitive to glucose absorption (Zeller, Novak, and Landgraf, 1989). However due to the short penetration depth of radiation at this frequency this method was not pursued for the non-invasive optical methods.
[0015] In order for a glucose measurement device to have the far-reaching impact described above it would have to meet several criteria. The first and most obvious criteria is that the process be painless. It would also not require a blood sample. The device would also need to provide nearly continuous measurement. In order for nearly continuous measurement to be achieved, the device would have to be very portable. With currently available technology, this means that the device should be implanted. These specifications and obvious safety concerns produce the following list of requirements that would have to be met by an ideal glucose-sensing device.
[0016] The device should fulfill the following requirements: high sensitivity, low power, fast response, safe for chronic use, does not consume what is being measured, miniaturizable, and does not require frequent calibration (Walsh, 1997). Further requirements for the present invention are that it reliably provides fast, accurate readings; not harmful to the patient; long-term stability; does not use blood samples; low power requirements; miniaturizable and comfortable; infrequent calibration requirements; will not fail without warning; can be operated by low-trained patients; possible interaction with an implanted insulin pump. What is needed, then, is a glucose monitoring system and apparatus that allows for tight control and low patient maintenance.SUMMARY OF THE INVENTION
[0017] A subcutaneous glucose sensor is provided which utilizes an infrared emitter which transmits light through a narrow sample of interstitial fluid held in a small sample trough. The sample trough is transparent to light at the necessary wavelength and is also highly inert. The device is implanted in the subcutaneous tissue and thus monitors interstitial fluid glucose levels, which have been shown to have a direct correlation to blood glucose levels. The present concept measures changes in absorption at mid-infrared frequencies (9-10 &mgr;m) due to glucose concentration changes. The sensor can be incorporated with an insulin pump in order to create an artificial pancreas.
[0018] One advantage of the present invention is that the best glucose measurement is one that allows the progress of diabetes complications to be checked, and a self-controlled implanted device minimizes patient maintenance. This device that can improve the lives of millions of diabetics around the world, by increasing glucose monitoring intervals and control, and reducing the pain and numbing effects of the current monitoring methods.
[0019] Other objects, features, and advantages of the present invention will become apparent upon reading the following detailed description of embodiments of the invention, when taken in conjunction with the accompanying drawings and the appended claims.BRIEF DESCRIPTION OF THE DRAWINGS
[0020] The invention is illustrated in the drawings in which like reference characters designate the same or similar parts throughout the figures of which:
[0021] FIG. 1 is a top schematic view of an apparatus according to a preferred embodiment of the present invention.
[0022] FIG. 2 is a side schematic view of an apparatus according to a preferred embodiment of the present invention.
[0023] FIGS. 3A and 3B are schematic views of the sample trough or well.
[0024] FIG. 4 is a graph of the light wavelength absorption.
[0025] FIG. 5 is a graph of the different attenuation wavelengths for various substances.DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0026] The operating parameters for the present invention define the design specifics of the device to a large extent. These parameters are defined by the location of the device within the body and the need for accurate and precise glucose measurement. Because the device is an implant it must be suitable for contact with the soft tissues within the body. The device must operate at body temperature, must not cause bleeding or scarring, and must not cause any great discomfort to the user. In addition the device must not allow itself to be harmed by the body, or must at the very least recognize when the body's response will prevent proper performance. The primary concern in this area is the fouling of the sample area with proteins.
[0027] In its most general embodiment, shown in FIGS. 1-3, a device 10 comprises a housing 20, which is preferably biologically inert when used in a patient's body. A power source 30 is preferably a battery which is preferably rechargeable. At least one, and preferably two energy sources 40 and 42, preferably a light emitting diode ("LED") or laser diode draws power from the power source. It is to be understood that other energy sources are contemplated as being within the scope of the present invention. The energy source preferably produces energy in the infrared region. At least one, and preferably two, band pass filters 50 and 52 filter energy from the energy sources 40 and 42 so that at least one, and preferably two, different wavelengths of energy are passed through the filters and to the sample 70. A sample trough 60 which can hold a sample 70 of fluid (not shown) is defined in the housing 20. At least one, and preferably two, light detectors 80 and 82 are positioned to receive transmitted energy passing through the sample trough 60. A microprocessor 90 can process the information received by the detectors 80 and 82. A telemetry device 100, associated with the device 10, functions as described hereinbelow.
[0028] The device 10 measures a range of glucose concentrations from about 20 mg/dl to about 600 mg/dl (Bayer, 1998). The accuracy of the measurements produced must be correct to within about 10 mg/dl of the actual value to compare to currently available glucose meters, although a closer range of +/−2 mg/dl is more desirable. This would require a test-retest precision that is considerably better than about 10 mg/dl. In order to ensure this accuracy, two redundant systems using different wavelengths of radiation are used in conjunction.
[0029] A schematic of a device 10 of the present invention is included in FIGS. 1-3. The dimensions of 8 cm by 3 cm by 1 cm are the currently generally accepted maximum allowable size for a subcutaneous implant (Herline, 1999). It is to be understood that larger or other shaped devices may be used by adapting current technology known to those skilled in the art and by designing the housing for use in a particular location in the body. Because the present technology contains no moving parts, most of this design could eventually be miniaturized to the size of a microchip. FIGS. 1-3 also show one configuration for the necessary components. One of ordinary skill in the art can modify the configuration for use with particular components. It is also possible that some of the components can be in a housing that is subcutaneous and some of the components can be in an external device in proximity to the subcutaneous housing, with communication between the two being achievable by radio frequency (RF) or other data communication medium known to those skilled in the art.
[0030] The function of the device components can be mapped by following the power flow through the device. The beginning for this flow is the rechargeable battery 30. Pre-processor circuitry then controls the power flow to the light sources 40 and 42. The light sources 40 and 42 convert the stored electrical energy to usable electromagnetic radiation at the specified frequency. This light radiation then passes through the interstitial fluid sample 70 where it is attenuated according to the concentration of glucose. The remaining light that passes all the way through the sample 70 is measured in the optical detector 80. The ratio of light detected to light emitted for both wavelengths is then passed to the post-processor where this data is fit to a mathematical model to determine the glucose concentration. This information is then passed out of the device 10 by the telemetry system 100.
[0031] The battery 20 is necessarily a high-tech component of the device 10. The style of battery which can preferably be used is already in use in pacemakers where a long term battery with a small size is needed. In order to accomplish this, the battery 20 can be recharged using an RF signal or by other signals known to those skilled in the art. This means that the battery can be recharged without removing the device and without puncturing the skin.
[0032] In order to conserve battery power the light sources must be efficient. An example of an efficient light source is a diode laser that will operate at the desired wavelength of light radiation and at body temperature. A light emitting diode can also be used when coupled with a narrow band pass filter. This type of light source can easily operate at body temperature, and can be configured for a broad range of frequencies before implantation. However, the power efficiency suffers greatly compared to a laser diode. The LED is preferably filtered to attain the needed frequency.
[0033] The light beams produced by the energy sources 40 and 42 are passed through a sample 70 of interstitial fluid that is contained in a sample trough 60. The trough 60 is open to receive interstitial fluid on the top of the trough. The width of the trough 60 is preferably set at 10 &mgr;m to allow for the maximum dynamic range of the signal. A different width trough 60 may be used when using a signal having a greater or lesser maximum dynamic range.
[0034] The calculations associated with this embodiment are reviewed in the following discussion. This discussion covers the optical concepts regarding absorption and Beers law that were utilized in the design of the present invention. When light interacts with a molecule it can do one of three things. It can be absorbed and re-radiated, transmitted; it can be scattered, deflected; or it can be absorbed. During absorption the energy from the incident photon is transferred to the molecule. Normally this energy becomes heat, although sometimes it can be used to drive a chemical reaction as in the case of photosynthesis.
[0035] In a non-scattering, absorbing medium the amount of light at any point along the light beam's path length will decrease with position. This decay is exponential in nature and follows Beer's Law.
[0036] Where Ex is the light energy at any position x along the light beam. Eo is the initial light energy incident on the medium and alpha, (a), is the linear attenuation coefficient.
[0037] The linear attenuation coefficient alpha is dependent on the concentration of the absorbing molecule in the medium. So that A=kc and the two are directly proportional. Therefore, as the concentration of the absorbing molecule increases the amount of light penetrating the medium to a given depth x will decrease exponentially. Over a small change in concentration it may be reasonable to approximate this decrease as a linear relationship.
[0038] The following calculations show the derivation of the sample path length. The definition of transmission is
[0039] Where T is transmission, Io is the incident light and It is the transmitted light. This is then used with Beer's Law:
l=1o*(eˆ (−a*1))
[0040] Where alpha, (a), is the attenuation coefficient and l is the path length. By substituting transmission into Beer's Law, the result is:
T=(eˆ (−al))
[0041] This can then be used in the formula for the power of the detected signal:
[0042] Where PS is the detected signal power and PO is the initial power. The dynamic range of the signal as glucose concentration changes is then
[0043] Where DR is the dynamic range, Tmax is the maximum transmittance with low glucose concentration and Tmin is the minimum transmission at high glucose concentration. By substituting the previous formula, one gets:
[0044] Where DR is the dynamic range, alowc is the attenuation coefficient at low glucose concentration and ahighc is the attenuation at high glucose concentration. Substituting in the experimental values for the attenuation coefficients and solving for the maximum dynamic range the optimal path length is found to be 10 &mgr;m.
l=10 &mgr;m
[0045] An additional factor to be considered is the Fresnell reflection. When any wave propagation of energy crosses from a medium of one impedance to a medium of a different impedance some of the wave is reflected and some of the wave is refracted. The portions of the wave that are parallel to the incident surface and the portions that are perpendicular to the incident surface behave differently so that there are two coefficients describing the reflection off the impedance mismatch.
[0046] When the light beam is orthogonal to the impedance mismatch the total reflectance coefficient simplifies to the following equation.
[0047] There is also an angle known as Brewster's angle where all of the light polarized perpendicular to the interface will be transmitted despite the impedance mismatch. This fact can be used to reduce the loss of power due to reflect at impedance mismatches.
[0048] Therefore, the depth of the trough 60 is determined by the spot size of the light beam. It is anticipated that diffusion will be sufficient to equalize glucose concentration within the sample area to that of the surrounding tissue. The substance that the sample trough 60 is made of will should be optically transparent to light in the region of interest. It must also be biologically inert. The two materials that have been highly considered for this application are sapphire and CVD diamond films. Glass or quartz of sufficient transparency and quality may be usable. The CVD diamond films have been chosen because they are easily produced compared to sapphire optical components. The trough volume has a practicable upper path length limit in that if too much fluid, e.g., water, is sampled, the high volume water may absorb the mid-IR light.
[0049] After light passes through the sample trough 60 it is measured by the detector 80. The primary limitation for this component is the ability to operate at physiological temperatures. This requirement led to the selection of a pyroelectric detector for this component. This type of detector absorbs pulsed light energy and measures the corresponding rapid temperature increase. Because the detector 80 is based on temperature differentials, it is very stable at biological temperatures and not affected by the gradual changes in body temperature.
[0050] The post-processor then interprets the output of the light detectors 80 and 82. The detectors have an analog voltage. This voltage is used to determine how much glucose is present in the sample aliquot. There is an inverse relationship between voltage and the concentration of glucose. The ratio of measured transmitted light to the light produced provides a value for the change in the transmission of light. This value can be correlated to glucose concentrations. In order to utilize the redundancy built into the system by including two wavelengths of light in separate detectors 80 and 82 the recorded transmission values for the two wavelengths can be reconciled using a microprocessor 90 that can recognize a wide range of inputs and properly deal with novel inputs that fall within a reasonable range.
[0051] A possible processing solution would be to use a neural networks application. This method was tested using arbitrary absorption ratios that are linearly proportional to a change in glucose concentration. Simple perceptrons were used to insure that the two wavelength absorption ratios were relatively close together. This would warn of failure if these two ratios are significantly different. The perceptrons worked moderately well and could be enhanced, but other comparators are possible to solve this problem.
[0052] The translation of the absorption ratios into glucose concentrations is linear. However, the neural network needs to approximate the function in a manner that allows for generalization between trained values. Back-propagation performs function approximation well as does radial basis function networks. The function was attempted with back-propagation, but the results were unsatisfactory with little convergence resulting. The radial basis function networks did converge and will give workable results. Initial conclusions show that this method can be used, but with 120 neurons for each network, the networks are larger than desired and should be modified if neural networks are to be used.
[0053] As a final safety precaution a telemetry system 100 is preferably built into the device to allow testing of the power system and device, calibration, and warnings when the device fails. A proper fail-safe mechanism for such a system requires a periodic signal and test from the device to ensure that it is working properly. If this signal is not received, an alarm is sounded on a companion pager style device 110 (not shown). This device 110 or other remote signaling device may also be used to read out the measurements obtained from the sensor. Such a signaling device 110 should be capable of receiving a signal transmitted by the device 10 and transmitting a detectable signal, such as, but not limited to, audible, display, vibration, combinations of these, or the like.
[0054] The final calculated glucose concentration is transmitted to a receiver 110, such as a pager device using spread-spectrum telemetry or other devices known to those skilled in the art. The information is coded and put on the correct frequency. Only the pager or other receiving device 110 has the correct key to interpret the information and it will not interpret other signals as good information without that key. This sort of telemetry allows for a low power signal to be used without concern for signal interruption. The technology necessary for this component has been produced at the Oak Ridge National Laboratories and has been placed on a single miniaturized microchip, with the exception of the antenna.
[0055] The entire device 10 is then encased in a bio-compatible sheathing or housing. This sheathing may be a Teflon® or other biologically inert, nondegradable coating similar to the material used to encase pacemakers. A new surfactant coating is currently under development at Case Western Reserve University that would improve the bio-compatibility of the device by making the surface of the device appear more like a cell membrane to the body (Ruegsegger, 1999). This type of surfactant coating could also line the sample trough to prevent fouling of the sample area with undesired proteins.
[0056] Safety concerns for the device 10 incorporate both those concerns normally associated with any type of implanted device and those normally associated with medical information systems. As an implanted device, it is critical that the device of the present invention not cause any harm to the body. This could be through toxicity, thermal damage, or through rejection. Toxicity is not a probable threat with an implanted device because no toxic substances are in contact with bodily fluids as in implanted chemical sensors. Whenever using an absorption based light-tissue interaction, thermal damage is a possibility. In this case the threat of thermal damage is greatly reduce by using low powered light sources and a small sample volume. The device 10 has also been designed so that the surface of the device 10 will remain at physiological temperature.
[0057] The more pressing area of safety concern deals with typical issues of medical information systems. Improper information can lead to an improper diagnosis. This is the reason for the redundancy designed into the present invention. By comparing two separate measurements the accuracy of the device and robustness of the measurement is greatly increased.
[0058] In the case of the present invention, there is also a need to warn the user before information from the sensor becomes unavailable. The user may become reliant on warnings from the sensor when their glucose levels are becoming too high or too low. If the device were to shut off without warning the user may fall into diabetic shock. This is the most significant safety issue. To provide a safeguard the telemetry system 100 of the device 10 can communicate with a pager-type device 110 that is carried with the user. This pager 110 can be used for reading glucose levels, and can also perform the function of self-testing the device 10. This could be performed by querying the device 10 and requiring an appropriate response. If the response is not received, an alarm could be sounded. This type of interaction could also be used for calibration of the sensor.
[0059] This embodiment provides a solution to the problem of providing a long term implanted glucose sensor. The combination of mid-infrared optical detection and an implanted sensor provide a sensor with unique beneficial aspects compared to other sensors under development. The two primary concerns currently associated with this device are the power concerns and the bio-compatibility issues. The long term power required to drive an LED light source can be more than can reasonably be expected from existing pacemaker style batteries. Development of an appropriate laser diode would be the greatest single improvement that could be made to alleviate this problem. However, other techniques may be available to improve the efficiency of the LED source system, such as finding the narrowest band source possible. It may also be possible to increase the power of the battery.
[0060] The biocompatability issue of concern deals with the fouling of the sample trough 60 with proteins. This would prevent interstitial fluid from diffusing into the sample trough 60. The use of the surfactant coating and CVD diamond may be enough to prevent fouling of the sample trough 60, but this has not been tested. An alternate method for avoiding this problem may be to introduce moving parts to the design and have the sensor clear the sample area with a small plunger of some sort.
[0061] In an alternative embodiment of the present invention is the incorporation of the device as a feedback mechanism in conjunction with and for an implanted insulin pump 200 (not shown). This provides a patient with a glucose measuring and insulin delivery system for controlling blood glucose levels. The combined system can provide insulin control that would allow the return of near normal functioning of the body. An insulin delivery apparatus as known in the art can comprise: (1) a reservoir capable of holding an amount of insulin, (2) means for delivering said insulin from said reservoir to a patient, said means comprising a pump, and (3) an insulin delivery processor for determining when to actuate said pump to deliver an amount of insulin.
[0062] Even if the device of the present invention is not used in conjunction with an insulin pump, it still provides a dramatic improvement over current methods. The patient cannot forget to take a blood measurement with this device, since measurement is automatic. In addition the measurement will be completely unobtrusive and painless once the implant is installed. This implant would also allow for measurement during periods of sleep and allow for early warning when glucose levels are heading toward dangerous levels.
[0063] The present invention also provides a method of detecting and measuring a component of a fluid, comprising the steps of (1) providing a device comprising a housing, a power supply, a processor, at least one energy source, at least one detector capable of detecting the energy emitted by the energy source, and at least one sample trough associated with the housing capable of retaining an effective amount of the fluid; (2) causing an aliquot of fluid to be retained within the trough; (3) emitting energy from the energy source so as to impinge on the fluid in the trough; (4) detecting the energy passing through the fluid in the trough; (5) transmitting an output signal from the detector to the processor; (6) interpreting the output signal; (7) determining the presence and/or concentration of the component in the fluid aliquot, and optionally (8) transmitting data containing the calculated concentration to a remote device.
[0064] The present invention can also be used to measure impurities in industrial applications. High temperature applications could be used, because the CVD diamond will work at high temperatures. The Teflon® coat may not be optimal for use above the Teflon® material softening or melting point temperature and that would have to change. Any water-based fluid will need to have a small path length, because water absorb highly in the mid-IR region. The peaks, like with the present invention, are much higher than the water, but too much water means all light absorbed.
[0065] Other fluids which can be measured need to have peaks that are not influenced by other changes in the environment. Hemoglobin, plasma, tears, semen, urine, other body fluids or semi-fluids and the like are possible body fluids which could have components measured according to the present invention. The present invention can also be used to detect and measure the presence and amount of particular proteins, amino acids, nucleotides, and the like that may increase concentration prior to the return of cancer. If the implantable device of the present were implanted after cancer the first time, then it could catch the spike in protein production associated with the return and get the cancer attacked again before any other conventional forms of detection have found the cancer returning. The present invention could also be used on a probe instead of an implant, as a better technique for biopsy.
[0066] Although only a few exemplary embodiments of this invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the following claims. It should further be noted that any patents, applications or publications referred to herein are incorporated by reference in their entirety.
[0067] The invention will be further described in connection with the following Examples, which are set forth for purposes of illustration only. Parts and percentages appearing in such Examples are by weight unless otherwise stipulated.EXAMPLES
[0068] The sensing method utilizes glucose modification. This sensing method was verified by experimentation. A first experiment used a concentration of glucose that was two orders of magnitude greater than physiological levels. This experiment was then modified to test for a measurable change in absorption due to glucose concentration changes at physiological levels.
[0069] The next experiment was conducted using a Bruker™ IFS 66 v to measure the reflectance spectrum of various samples. The samples measured were of plasma at varying glucose concentration and several aqueous glucose solutions of varying concentration. The glucose concentrations used were all within the normal physiological range with the exception of one sample of higher concentration that was used to compare to the previous experiment.
[0070] This resulted in proof of the concept of using absorption in the mid-infrared range to measure changes in glucose concentration. There was a definite linear increase in absorption in the 8.5 to 10.5 &mgr;m wavelength range with increasing glucose concentrations. FIG. 4 shows the increase in absorption for the primary (9.62 &mgr;m) and secondary (9.02 &mgr;m) peaks. These measurements were taken at room temperature (˜25° Celsius), not body temperature, so the water absorption seen in the diagram will shift more to the right when implanted in the body. This is a result of the hydrogen bonding in the water, which is stronger at colder temperatures. The linear increase in absorption is not shown on the diagram but was evident in the results. Differential changes in glucose concentration were measurable by observing the increase in absorption relative to the base-line curve. The differential method shown in FIG. 5 showed a better correlation to changes in glucose, especially smaller changes, with an R2 equal to 0.98. Glucose concentrations of 2.4 mg/dl were distinguishable with this method.
[0071] Using the FIFTIR machine, we were able to have similar results to Zeller et al. and make similar conclusions. The following major absorption at the wavelengths of 9.62, 9.02, 9.26, and 10.1 &mgr;m were observed. The wavelengths for glucose absorption that were chosen as the most significant and most usable were 9.02 &mgr;m, 9.26 &mgr;m and 9.62 &mgr;m. The 9.62 &mgr;m peak had the strongest absorption and when compared to the Zeller et al. paper was not present in blood either. The 9.26 &mgr;m peak had the next largest peak, but this peak is also found in other blood proteins, hemoglobin and albumin (Zeller et al., 1989). The 9.02 &mgr;m was smaller than the previous two peaks but &mgr;sable. This peak too can be found in hemoglobin (Zeller et al., 1989). However, as mentioned above, the design of the present invention will measure the interstitial fluid, which is closely related to plasma, and not blood. The plasma did not have the absorption peaks of hemoglobin, so the 9.02 &mgr;m wavelength can be used as well (Zeller et al., 1989). The 9.26 &mgr;m wavelength is still hindered by the absorption interference of albumin even with hemoglobin accounted for. If it is shown that the albumin is relatively constant, or does not significantly effect the level of absorption, then the 9.26 &mgr;m peak may also be considered. Only two peaks are needed for the preferred embodiment, so the 9.02 &mgr;m and the 9.62 &mgr;m are used.
1. A device for sensing the presence or concentration of a component in a fluid, comprising:
- a. a power supply;
- b. a processor;
- c. at least one energy source;
- d. at least one detector capable of detecting energy emitted by said energy source;
- e. at least one sample trough capable of retaining an aliquot of fluid; and,
- f. a housing.
2. The device of claim 1, further comprising a telemetry device associated with said processor and capable of transmitting a signal from said processor to a remote receiving means.
3. The device of claim 2, wherein said remote receiving means is a pager capable of detecting a signal from said telemetry device.
4. The device of claim 3, wherein said signal transmitted from said telemetry device is an alarm signal transmitted in response to failure of said device to obtain measurements.
5. The device of claim 1, wherein said signal contains measurement data from said detector.
6. The device of claim 1, wherein said energy is light.
7. The device of claim 1, wherein said energy source is a light emitting diode.
8. The device of claim 1, wherein said energy source is a laser diode.
9. The device of claim 1, wherein said energy source generates energy in the near infrared range.
10. The device of claim 1, wherein said energy source further comprises a filter.
11. The device of claim 10, wherein said filter comprises a narrow bandwidth pass filter.
12. The device of claim 1, wherein said energy source provides energy at least two detectably distinct wavelengths.
13. The device of claim 1, wherein said detector is capable of detecting transmitted energy in the near infrared range.
14. The device of claim 1, wherein said detector is a pyroelectric detector.
15. The device of claim 1, further comprising a second detector capable of detecting a distinct wavelength of energy.
16. The device of claim 1, wherein said power supply is a battery.
17. The device of claim 1, wherein said battery is rechargeable.
18. The device of claim 1, wherein said trough is generally U-shaped and is defined in said housing.
19. The device of claim 1, wherein said trough is coated with a surfactant.
20. The device of claim 4, wherein said light has a wavelength of the mid-infrared.
21. The device of claim 4, wherein said light has a wavelength of from about 9 &mgr;m to about 10 &mgr;m.
22. The device of claim 1, wherein said component is glucose.
23. The device of claim 1, wherein said fluid is hemoglobin, plasma, tears, semen, or urine.
24. An apparatus for delivering insulin and sensing the presence or concentration of glucose or other component in a fluid, comprising:
- a. a power supply;
- b. a processor;
- c. at least one energy source;
- d. at least one detector capable of detecting energy emitted by said energy source;
- e. at least one sample trough capable of retaining an aliquot of fluid;
- f. a housing; and,
- g. an insulin delivery apparatus comprising
- i) a reservoir capable of holding an amount of insulin,
- ii) means for delivering said insulin from said reservoir to a patient, said means comprising a pump, and
- iii) an insulin delivery processor for determining when to actuate said pump to deliver an amount of insulin,
- such that said insulin delivery processor is in communication with said device processor to provide a feedback loop between said sensing device and said delivery apparatus to maintain proper insulin level.
25. A method of detecting and measuring a component of a fluid, comprising the steps of:
- a. providing a device comprising
- iv) a housing,
- v) a power supply,
- vi) a processor,
- vii) at least one energy source,
- viii) at least one detector capable of detecting the energy emitted by the energy source, and
- ix) at least one sample trough associated with the housing capable of retaining an effective amount of the fluid;
- b. causing an aliquot of fluid to be retained within the trough;
- c. emitting energy from the energy source so as to impinge on the fluid in the trough;
- d. detecting the energy passing through the fluid in the trough;
- e. transmitting an output signal from the detector to the processor;
- f. interpreting the output signal;
- g. determining the presence or concentration of the component in the fluid aliquot.
26. The method of claim 25, further comprising a step h. transmitting data containing the calculated concentration to a remote device.
Type: Application
Filed: Jan 26, 2001
Publication Date: Feb 7, 2002
Inventors: W. Blake Martin (Birmingham, AL), Micah D. Schmidt (Burtonville, MD)
Application Number: 09770131
International Classification: A61B005/00;


text:
100g Packet Premium Holi Color Powder
Our 100g Packets are our smallest option. They are perfect for small parties and gender reveals.
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Our holi powder is colored cornstarch made from 100% safe non-toxic food grade dyes. Throw your own color powder run or fundraiser with our 100g packets.
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Want a wholesale 100g bags? Check out our 100g 70 Pack

subset: commoncrawl


text:
Bhanu Awasthi1, Sunil Kumar Raina2, Vivek Negi1, Narvir Singh Chauhan3, Sandeep Kalia1
1 Department of Orthopaedics, Dr R.P.G.M.C, Tanda, Himachal Pradesh, India2 Department of Community Medicine, Dr R.P.G.M.C, Tanda, Himachal Pradesh, India3 Department of Radiodiagnosis, Dr R.P.G.M.C, Tanda, Himachal Pradesh, India
Click here for correspondence address and email
Background: A mismatch between the prosthesis size and bone may result in a number of complications. Keeping this in view, it is essential to analyze the morphological differences of the knee observed across various ethnic groups to improve the performance of total knee arthroplasty (TKA). The current study was aimed at studying the computed tomography (CT) profile of distal femur in Indian population and evaluates it morphologically. Materials and Methods: This descriptive study was conducted on 62 patients presenting to the Department of Orthopedics in a tertiary care center in rural north-west India for features suggestive of osteoarthritis and trauma of knee from September 17, 2015 to September 16, 2016. Helical CT of both knees was done, and the data were analyzed using Statistical Package for Social Sciences Version 17.0 statistical significance was assessed with the help of t-test and the value of P < 0.05 was considered to be statistically significant. Results: The mean mediolateral (ML) value in male patients was 72.74 ± 4.45 while the mean ML value in female patients was lower (63.59 ± 2.61). The mean anteroposterior (AP) value in male patients was significantly (statistically) higher (49.62 ± 3.86) in comparison to mean AP value in female patients (45.11 ± 4.4). The mean anterior lateral condylar height (ALCH) value in male patients was higher (17.53 ± 2.72) in comparison to mean ALCH value in female patients (14.63 ± 3.42). Conclusions: The current study highlights the need to develop components and implants for use in TKA and fractures of distal femur keeping the age- and sex-specific anatomical features of people of different ethnic origins in view.
Keywords: Helical computed tomography, lower end femur, morphometric, study
Correspondence Address:Dr. Sunil Kumar RainaDepartment of Community Medicine, Dr R.P.G.M.C, Tanda, Himachal Pradesh IndiaSource of Support: None, Conflict of Interest: NoneCheckDOI: 10.4103/ortho.IJOrtho_136_17
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ortho.IJOrtho_136_17


text:
The Als have eight picks, but they don't own a first-rounder. Former GM Jim Popp traded it to the Lions for the rights to QB Vernon Adams.
GM Kavis Reed optimistic about Alouettes' draft prospects
It likely will be with a twinge of resentment and anxiety come Sunday night when Kavis Reed — suddenly with time on his hands — sits back and listens for which player British Columbia selects third overall in the Canadian college draft.
"It's going to be difficult, but the reality is we don't have that pick," the Alouettes' general manager admitted. "I'd be lying if I said we haven't thought (what would happen) if we had this pick. That's human nature."
The Canadian Football League's annual draft, consisting of eight rounds, goes Sunday night (7 p.m., TSN, RDS). Although the Als have eight selections, they don't own a first-round pick. Former GM Jim Popp traded it to the Lions last May for the rights to quarterback Vernon Adams. Montreal missed the playoffs with a 7-11 record, meaning B.C. selects third overall.
This marks the first time since 2012 — and only the third time since the franchise was resurrected in 1996 — the Als haven't had a first-round pick.
While Reed suggests there's enough depth for the Als to get a good player with their first choice, 12th overall in the second round, don't be surprised if Montreal swings a trade to secure an earlier pick. Indeed, according to a source, the Als will entertain that option to select Carleton receiver Nate Behar, although he's a relatively modest 5-foot-11 and 204 pounds.
Many believe Behar is one of the top two eligible receivers. Although his ranking among the CFL's scouting bureau inexplicably dropped throughout the season, he was a first-team all-Canadian and Ravens team captain.
Should Reed be seeking a dance partner for a trade, Winnipeg and B.C. have two picks in the opening round. The Blue Bombers have the first overall choice via a trade with Toronto for quarterback Drew Willy. Winnipeg's expected to select Faith Ekakitie, a defensive lineman who played at Iowa.
While some GMs seek character in prospects, Reed's more concerned about how a player will fit into the Als' scheme.
"There's never going to be the perfect player," Reed said. "Where can the coaches take a player? Do they have certain qualities the coaches are looking for? If they're deficient in certain areas, can they be coached up to the next level?"
Reed said he's looking to fortify the team's linebacking corps, especially seeking someone who can play on special teams. He'd also like to add a defensive back through the draft and always has his eye on offensive linemen.
One linebacker who has flown under the radar is Cameron Judge, who was born in Montreal but qualifies as a non-import although his family moved to California and he played at UCLA. The 6-foot-2, 235-pounder is considered an explosive athlete. Although he didn't play much on special teams due to the Bruins' depth, he was used extensively on special teams.
Another potential pick in the second round could be Randy Colling, a 6-foot-5, 320-pound defensive tackle originally from Hamilton who played at Gannon, a Division II university in Erie, Pa. Colling, about to turn 27, has been playing in the Arena League where one of his teammates, Brian Brikowski, is a former Alouette.
"All of our preparation pretty much has been we're picking 12th overall," Reed said. "We make our scenarios based on that reality.
"But if we need to move a few spots up, we're prepared to make offers to do that. There's enough depth that we're going to get a very good player at 12, we believe."
Two of the leading defensive backs are considered to be Calgary's Robert Woodson and Dondre Wright, who played at Henderson State. While Woodson's a traditional safety, considered athletic and fast, Wright is more suited to playing in the box, as a linebacker, which would suit defensive coordinator Noel Thorpe's scheme.
The top three rated players, according to the CFL, are all headed to the NFL and will likely be selected in the middle to later rounds on Sunday. Montreal's Justin Senior, an offensive tackle from Mississippi State, was selected by Seattle in the sixth round. Eli Ankou, a UCLA defensive lineman, signed a priority undrafted-free-agent deal with Houston, while Geoff Gray, an offensive lineman from Manitoba, did likewise with Green Bay.
Laval tight-end Antony Auclair, ranked seventh by the CFL, signed with Tampa Bay.
"The NFL got it right in terms of who the best guys are. Those are the elite guys," said TSN analyst Duane Forde. "It'll be interesting to see where those guys fall. They all have a pretty good chance of sticking there for at least a year."
While the draft's deep in offensive linemen and defensive tackles, it's considered more top-heavy. Next year's crop is likely better.
"Nine CFL teams could all have different boards with their top 30 prospects," Forde said. "There will be more variation. There are guys some teams see as high first-rounders that other teams see as fourth-rounders, and vice versa."


text: Resources Prayers This Week in Prayer: North East Africa North East Africa is a challenging region in so many ways. Feba UK partners in a variety of media projects in which programmes are produced to address the physical, social and spiritual issues for audiences in remote communities, living in restrictive environments as well as those facing challenging life situations. SUNDAY 18th November A listener writes: "I am listening to your programmes but when I do I hide myself from my family because they are against me." Please pray for listeners who do not have freedom to learn about Jesus or worship openly. Pray that God will strengthen them in their situation. MONDAY 19th November Please pray for the follow-up worker of one of the daily language broadcasts. He was rejected by his community and relatives because of his faith but recently his relatives contacted him and they met together. Please pray for their openness to him and his faith, and for the relationship to be restored. TUESDAY 20th November Give thanks for two people who are planning to join the team as producers. Pray for them as they apply for work permits, that their applications would be looked on favourably by government officials. WEDNESDAY 21st November A partner ministry in North East Africa has had one of its projects, which was effective in reaching a community, closed down by the local authorities. Please pray that God would open other ways for them to work among this community and for the partnership to continue. THURSDAY 22nd November There have been ethnic conflicts in some areas of the region resulting in many people being displaced and some deaths - listeners have been affected by this situation. Please pray that God will intervene, comfort and strengthen them. FRIDAY 23rd November "One of your listeners shared with me about the way of salvation. He also informed me about your radio programme . . . Now after listening to your programme I clearly understand God's plan for me and decided to receive Jesus as my personal Saviour." Give thanks for this listener and others who come to faith through the radio programmes. Pray that many more will respond. SATURDAY 24th November Please pray for A Friend in the Wilderness shortwave programme, broadcast into a closed country where believers are living under pressure. Pray that the programme will be an encouragement to them and restore their hope in God.


text:
Bombay Paperie is a boutique in Fort that specialises in paper products made from recycled cotton pulp. The sophisticated store stocks notepads, greetings cards, lanterns, folders, gift bags, and crafting kits in a dizzying array of colours and designs, which make for brilliant presents.
Bombay Paperie, 63, Bombay Samachar Marg, Fort, Mumbai 400 001. Phone: 022 6635 8171
I'm already entranced by the heritage building on Bombay Samachar Marg and the fresh, papery smell cutting through the store does the rest. As I step into Bombay Paperie, I'm immediately enveloped in deep hues of purple, teal, and mustard. My mind starts clearing space in my cluttered bedroom for compact folding lanterns in pretty shapes and pastel shades. In their warm glow, I notice mobiles of varied hues and textured wall art. Stiff paper bags stand at the centre of a large wooden table embellished with enticing stationery. Greeting cards gleam with golden prints of leaves, twines, and mangoes, bundles wrapped with twine and a single paper flower – a white rose that now dangles between Virginia Woolf and Jigme Khesar on my soft board.
The room at the back is filled with rough-edged wrapping paper hanging from vintage towel racks and stacked against the wall in multi-coloured towers. Black and white photographs capture the unique paper-making process, a practice dating back to the Mughal era. The paper at Bombay Paperie is made from cotton pulp, a by-product of cloth manufacturing. After days of soaking and slow beating at the Daulatabad unit, the pulp is transformed into sheets of handmade paper, which are then transported to Ahmedabad for sprucing. Experienced craftsmen use hand-carved wooden blocks to print modern and traditional designs before the paper makes its way to Mumbai.
As sullen brokers spill out of the Bombay Stock Exchange across the street, I make my way to the cashier, overflowing basket in one hand, credit card in the other. I'm ready to swipe plastic for paper treasures.


text:
The owner of Hart's tourbus claims he was attacked by the drummer
The Examiner reports that an arrest warrant has been issued for Hart relating to an alleged assault on Cecil "CJ" Curtsinger, who owns the tourbus which Hart is currently using.
Curtsinger claims that the incident took place after a Mickey Hart Band show at Terrapin Hill Farm in Kentucky when he was summoned to the tourbus before Hart "threw me down, started [to] cuss [at] me, hitting me, pushing me around then told me to get off MY bus."
Hart, who is currently in Arkansas, has dismissed the allegations, saying on his Facebook page "I am totally baffled by a bizarre claim of assault by me coming out of Kentucky – the home of Bluegrass and a state I love dearly. Any accusation or claim of assault against me is completely false and without any basis whatsoever. I played drums on 'Shakedown Street,' but I never expected to be 'The Victim or the Crime.'"


text:
WTWO Special Report: Inside the K2 Craze, Part 2
By: DAVID SHEPHERD [firstname.lastname@example.com] – Monday, August 16, 2010
TERRE HAUTE, IN – In part one of our special report on K-2, we introduced you to a new craze that is sweeping the nation; using a chemically altered herb to get high and in some states, like Indiana, it's legal. Or is it?
More on that in a moment. As I researched this story, I met some K-2 users who say they love the herb.
One marijuana smoker even told me he prefers the high he gets off of K-2 but without knowing what company is manufacturing it and exactly what's in it, health officials say the risk greatly outweighs the reward.
Clay County's Chief Deputy, Rob Gambill says, "There's already been hundreds of cases of ER visits, calls to poison control and so fourth."
On streets and in towns across Indiana, those who make the laws and those who enforce the laws are warning people about the effects of K-2.
"It's also more dangerous than marijuana apparently so I imagine it's going to be vigorously pursued," explains Gambill.
State Representative Clyde Kersey (D-Terre Haute) says, "K-2, as I understand it, is a chemical that was developed in a lab. It's a synthetic marijuana and yet it's legal to buy across the counter and teenagers have access to it."
Stores and gas stations that sell K-2 say they don't sell the herb to anyone under 18-years-old but Kersey says, just like cigarettes, the K-2 is getting into the hands of kids much younger. "There've been young people as young as 14 that have been admitted to the hospital with the affects of K-2."
And the warning from police: before you spend your money on the chemically altered herbs, know that it may already be illegal.
"According to one of the Controlled Substances Acts in Indiana, any drug that mimics the effects of another drug is an illegal drug," explains Gambill. "This mimics the effects of marijuana which is already illegal."
So if it may already be illegal, why don't the police arrest the users and the sellers?
Some cops say, they don't know if they can but they warn if you get caught smoking K-2, they will investigate it.
Gambill says, "[We'll] make the report, let the prosecutor make that decision since it's kind of a murky area right now. We want to be more cleared up before we take somebody to jail."
But those who enjoy smoking K-2 are happy it's so easy to get their hands on and they're giving it rave reviews on the internet, where blog post after blog post pour in from people who've tried the synthetic marijuana; and who like it.
But the easy access they welcome may not be around very long. Lawmakers in Indiana are already talking about actions they can take to make K-2 illegal in the next legislative session.
Kersey says, "It should be banned at least until we know what the effects are and whether we want this drug on the market."
This herb is sprayed with a chemical and there is not one source that can tell us what it actually is and while users may enjoy the high, without knowing what you're putting in your body, it can be a dangerous gamble. It's definitely something law enforcement and legislators are trying to get a better understanding of.


text:
Return Policy
Thank you for shopping on azzraworld.com, we hope you love your purchase. However if you have any issues with the
goods themselves or have questions, please call us on +91 9660 444 000or drop us an email email@example.com here and we will get back to you.
All returns must be
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If you return items to us that do not comply with the above requirements, we will return them to you at your cost.
What you Need?
Keep the original receipt you receive in your parcel or in store.


text:
Mazda is the best car brand in the USA for the fifth year in a row - Days after scoring high on reliability rankings from Consumer Reports, the Japanese car manufacturer Mazda will take home the title of Best Car Brand.
I don't put much stock in US News and World report. Surprised they're still around. No longer in print, just on-line.
I moved into my current home in 2010 and was buying all new appliances, so I subscribed to CR.
Wherever there was at least 20 User Reviews for an appliance, I included them in my data set and graphed them out. The visual was quite surprising. It looked like an "X." Nearly everything CR rated as high, Users rated as low, and vice versa. They were diametrically opposed. Of course, I did not renew my subscription.
I've wanted to upload those graphs whenever someone posts a CR article just to lend perspective, but I must have deleted them.
It's funny, I've got friends who would never make a major purchase of a product lacking a solid CR endorsement.


text:
Marvel Absolutely Everything You Need To Know Hardcover
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|Adam Bray
|DK Publishing
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|Book Description
|Marvel Absolutely Everything You Need To Know is packed with fun facts, bizarre-but-true tales, and quirky insights into everyone's favorite Marvel comic characters, including The Avengers, Spider-Man, and Daredevil. Discover why the Hulk comes in three different varieties--green, gray, and red--and how a frog once gained Thor's powers! This unique guide sheds light on the most fascinating corner of the Marvel Comics Universe, from secrets of the Super Heroes to the making of Marvel's finest and strangest comic moments. From behind-the-scenes revelations to strange and interesting facts, Marvel Absolutely Everything You Need to Know will surprise and delight new and die-hard Marvel fans. (c) 2016 MARVEL
|About the Author
|Adam Bray is a frequent contributor to DK Star Wars(TM) and LEGO(R) Star Wars books, including Ultimate Star Wars and the best-selling Star Wars: Absolutely Everything You Need to Know. Visit him online at https: //twitter.com/authoradambray. New York Times bestselling author John Sazaklis enjoys adventures of his favorite characters. To him, it's a dream come true! By day, John is a somewhat mild-mannered art director and designer at a publishing house. He has also illustrated Spider-Man books and created toys used in MAD magazine. John lives with his equally (if not more) super-powered, beautiful wife and daughter in New York City. You can check out his blog at Sazmagic.blogspot.com and follow him on Instagram at @johnnysaz. Lorraine Cink is a comedian and writer for Marvel's weekly web shows, The Marvel Minute, THWIP! The Big Marvel Show, and Marvel Top 10. When not cracking jokes on stage, red carpet, or screen; Lorraine is a serious Marvel expert who really knows how to make her deep knowledge accessible and entertaining to a wide audience. She lives in the home of Super Heroes, New York City. Follow her adventures @lorrainecink.
|Number of Pages


text:
MinIO Quickstart Guide
MinIO is an object storage server released under Apache License v2.0. It is compatible[1] with Amazon S3 cloud storage service. It is best suited for storing unstructured data such as photos, videos, log files, backups and container / VM images. Size of an object can range from a few KBs to a maximum of 5TB.
MinIO server is light enough to be bundled with the application stack, similar to NodeJS, Redis and MySQL.
[1] MinIO in its default mode is faster and does not calculate MD5Sum unless passed by client. This may lead to incompatibility with some S3 clients like s3ql that heavily depend on MD5Sum. For such applications start MinIO with
--compat option.
minio --compat server /data
Docker Container
docker pull minio/minio
docker run -p 9000:9000 minio/minio server /data
docker pull minio/minio:edge
docker run -p 9000:9000 minio/minio:edge server /data
Note: Docker will not display the autogenerated keys unless you start the container with the
-it(interactive TTY) argument. Generally, it is not recommended to use autogenerated keys with containers. Please visit MinIO Docker quickstart guide for more information here
Install minio packages using Homebrew
brew install minio/stable/minio
minio server /data
NOTE: If you previously installed minio using
brew install miniothen it is recommended that you reinstall minio from
minio/stable/minioofficial repo instead.
brew uninstall minio brew install minio/stable/minio
Binary Download
|Apple macOS
|64-bit Intel
chmod 755 minio
./minio server /data
Binary Download
|64-bit Intel
wget https://dl.min.io/server/minio/release/linux-amd64/minio
chmod +x minio
./minio server /data
wget https://dl.min.io/server/minio/release/linux-ppc64le/minio
chmod +x minio
./minio server /data
Microsoft Windows
Binary Download
|Microsoft Windows
minio.exe server D:\Photos
Install minio packages using pkg
pkg install minio
sysrc minio_enable=yes
sysrc minio_disks=/home/user/Photos
service minio start
Install from Source
Source installation is only intended for developers and advanced users. If you do not have a working Golang environment, please follow How to install Golang. Minimum version required is go1.12
GO111MODULE=on go get github.com/minio/minio
Allow port access for Firewalls
By default MinIO uses the port 9000 to listen for incoming connections. If your platform blocks the port by default, you may need to enable access to the port.
For hosts with iptables enabled (RHEL, CentOS, etc), you can use
iptables command to enable all traffic coming to specific ports. Use below command to allow
access to port 9000
iptables -A INPUT -p tcp --dport 9000 -j ACCEPT
service iptables restart
Below command enables all incoming traffic to ports ranging from 9000 to 9010.
iptables -A INPUT -p tcp --dport 9000:9010 -j ACCEPT
service iptables restart
For hosts with ufw enabled (Debian based distros), you can use
ufw command to allow traffic to specific ports. Use below command to allow access to port 9000
ufw allow 9000
Below command enables all incoming traffic to ports ranging from 9000 to 9010.
ufw allow 9000:9010/tcp
For hosts with firewall-cmd enabled (CentOS), you can use
firewall-cmd command to allow traffic to specific ports. Use below commands to allow access to port 9000
firewall-cmd --get-active-zones
This command gets the active zone(s). Now, apply port rules to the relevant zones returned above. For example if the zone is
public, use
firewall-cmd --zone=public --add-port=9000/tcp --permanent
Note that
permanent makes sure the rules are persistent across firewall start, restart or reload. Finally reload the firewall for changes to take effect.
firewall-cmd --reload
Test using MinIO Browser
MinIO Server comes with an embedded web based object browser. Point your web browser to http://127.0.0.1:9000 ensure your server has started successfully.
Test using MinIO Client
mc provides a modern alternative to UNIX commands like ls, cat, cp, mirror, diff etc. It supports filesystems and Amazon S3 compatible cloud storage services. Follow the MinIO Client Quickstart Guide for further instructions.
Pre-existing data
When deployed on a single drive, MinIO server lets clients access any pre-existing data in the data directory. For example, if MinIO is started with the command
minio server /mnt/data, any pre-existing data in the
/mnt/data directory would be accessible to the clients.
The above statement is also valid for all gateway backends.
Upgrading MinIO
MinIO server supports rolling upgrades, i.e. you can update one MinIO instance at a time in a distributed cluster. This allows upgrades with no downtime. Upgrades can be done manually by replacing the binary with the latest release and restarting all servers in a rolling fashion. However, we recommend all our users to use
mc admin update from the client. This will update all the nodes in the cluster and restart them, as shown in the following command from the MinIO client (mc):
mc admin update <minio alias, e.g., myminio>
Important things to remember during upgrades:
mc admin updatewill only work if the user running MinIO has write access to the parent directory where the binary is located, for example if the current binary is at
/usr/local/bin/minio, you would need write access to
- In the case of federated setups
mc admin updateshould be run against each cluster individually. Avoid updating
mcuntil all clusters have been updated.
- If you are updating the server it is always recommended (unless explicitly mentioned in MinIO server release notes), to update
mconce all the servers have been upgraded using
mc update.
mc admin updateis disabled in docker/container environments, container environments provide their own mechanisms for updating running containers.
- If you are using Vault as KMS with MinIO, ensure you have followed the Vault upgrade procedure outlined here: https://www.vaultproject.io/docs/upgrading/index.html
- If you are using etcd with MinIO for the federation, ensure you have followed the etcd upgrade procedure outlined here: https://github.com/etcd-io/etcd/blob/master/Documentation/upgrades/upgrading-etcd.md
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- MinIO Erasure Code QuickStart Guide
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aws-cliwith MinIO Server
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s3cmdwith MinIO Server
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minio-goSDK with MinIO Server
- The MinIO documentation website
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Have you ever suffered from disastrous wind damage on your roof recently? If you are concerned about high wind advisories present in your area, then you definitely need to have your roof fixed or even replaced as soon as possible. However, during the procedure, your roofing professional may cite to you the chance of adding roof gables which were not present before. Let us learn more about these roof gables.
What Separates Them from the Others?
The expression "gable" is used to recognize the exact triangle-shaped wall located on a sloped roof. However, it is essential to say that the roof itself is not the gable. Together with a sloped roof, you may also want to consider having a gabled roof on your home. It is also easy to confuse the triangular portion of a gambrel roof for a roof gable.
Where Did the Name Come from?
The term for roof gables will not be made possible without the Greeks and the Germans. It is believed that the word itself first came from the Greeks, who happen to have a word 'kephale' which is defined as head. The Germans, on the other hand, have another word that does not only sound the same, but it is also almost spelled identically: gabel. So, now that we have a bit more background and context to help us understand what roofing gables are and what function they serve, let us discuss a few of the most common types you will discover:
What Are Some Common Types?
Location: Roof gables are not exclusive to houses. Any construction can be made to possess this kind of roof. You may observe a gable on the front part of the roof, or even around the other side. From time to time, a roof can be cross-gabled. A cross-gabled roof means that the gable usually rests on both the front and on the side instead of one or the other. Both of these gables are linked by what is called a valley roofing.
Porches: Most of the time, porches can promote roof gables too, along with dormers. Even though the expression dormer may be unknown to you, you can simply consider it this way: gable dormers are dividers to your gables themselves.
Pediment roof gables are more of decorative and stylish compared to most gables that only helps support the roof. In addition, it is also possible, and sometimes even more desirable, to create your roof gables more complicated as part of improving your home's aesthetic. In cases like this, the outcomes have been all either parapets or even corbiesteps.
Contact The Experts!
Here at George Kent, we have trained experts and seasoned professionals that are capable of providing you with your roofing needs. If you are interested in having your roof installed with roof gables, repaired, replaced, or would like an estimate, contact us directly or online. We are hoping to hear from you real soon!


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I was really silly for coining this Thursday Recycled Art day, I'm beginning to see. We do our craft project sometime during the week- its not always on a Thursday. This week it was actually on Monday, which makes the fact that I'm posting this so late sound really bad. I've been distracted. There's this thing called The Sketchbook project, it's run by the Brooklyn Art Library and I've barely now heard about it. What the sketchbook project does is allow anyone to participate in filling up a notebook that they send to you with drawings and such based on the theme that you pick. The sketchbooks then tour around the country, thousands of them are exhibited at galleries and museums. The fee to join is $25 and the deadline to join is October 31st. My theme is "You'd be home already." I was auctually on Katie Wall's blog and she led me to it. Don't you just love blogs? Anyway, the sketchbook project is right up my alley and as soon as I read about it I had to be a part of it. It was 6am when I read the post and I was so afraid that I wouldn't be able to do it, I was so anxious to click the button and have the materials sent to me I could've cried. But I waited til I heard my husband stirring and practically pounced on him about it. Then of course I had to re-explain,wait for him to fully wake up, show him the site and then he said yes, which absolutely made my week. Now I'm anxiously awaiting the arrival of the notebook so that I can begin. A little about our art project this week below-
Sometimes my kids dont feel up to doing the project I've thought up for us. And that's ok. The purpose of our projects is not "perfection" , the purpose is for my children to feel they have a free enviroment in which to create. So when I suggested that we use an old Ramen noodle box(please don't judge but, sometimes my husband and I stay up all night and eat Ramen noodles), paint it blue and make an ocean diorama, Cat wasn't feeling it. Really? because we could paint it blue then make fish and hang them from the top of the box-it'd look like they were swimming! Cat,"Nah, fish are kinda boring and that looks like a house…can I paint the roof blue? " And I consented, and when I asked if she wanted to make people or animals to go inside her house?She asked if she could draw the ICarly cast. So there you go, feautured above is an Icarly house complete with Carly, Freddie and Sam. We glued the finished characters onto toliet paper rolls so they could stand up better. Next? She's wanting to make a house for Pucca and her friends, because apparently, ninjas and the Icarly cast cannot share a house, they just can't! You learn something new everyday.(And honestly, the fish things been done before, but an Icarly tissue roll and Ramen noodle box set? Quite possibly, not.) 🙂


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Check out the University Christian Ministry's new website for pictures from some Better Together events they cosponsored, like this one from the Faces of Homelessness Panel!
Latest Entries »
A huge thanks to the Office of the Chaplains for putting together this cute little slideshow of Religious Life 2011. Take a look and see if someone you know made the cut!
So, I just sat in a room of 140 people doing interfaith dialogue. For those of you who know me even a little I think you can understand how exciting I find that. This group was racially, sexually, religiously diverse, as well as diverse in age and gender. At my table in particular were two chaplains, a bishop, the chair of The Council of Islamic Organizations of Greater Chicago AND Judy Valente who is a religion reporter for PBS and NPR (my dream job). So there I was – in a room filled with people I respect and hope to grow up to be – with people I love (my closest friends and roommates were all there) doing the thing I love to do most (interfaith!) – and that's not even what made my night great.
No, the best part was actually the breakdown. I'd been DREADING breaking the event down. Do you know how hard it is to roll large round tables across Parkes 122? Do you know how heavy stacks of chairs get?
AND THEN you have to somehow put those heavy stacks of chairs on these God-forsaken rollie things that always seem to elude you and your chair stack the first few times around. When the Better Together Campaign kicked off in the fall, I was doing most of this with only a small group of dedicated helpers. But this time around, after a year of building relationships and getting to know people, I had a ton of help! Interfaith help! And instead of being frustrated, we laughed.
I raced, Ala, a new Palestinian Muslim friend I've made through doing this work, down the banquet hall rolling our tables until we both nearly lost control of them. My roommate (though we prefer the term "domestic partner") Shireen and I took pictures of ourselves and made faces as we cleared tables and folded table cloths.
I was thrilled. It finally dawned on me at that moment that Better Together has really worked at Northwestern. I'm so much more together with all these people than I was before. It's awesome.
So, here are some snapshots of our night. Take a look at the committed interfaith players on this campus — these kids are great! If you don't know them, you're missing out.
It is said that Evanston is the "City of Churches." In a sense I have come to know the truth of such a statement because over the last few weeks I have been interviewing pastors and worshipping with their congregations as part of my research for a journalism project I'm working on. But, I have also been interviewing non-Christian spiritual communities, like Udumbara Zen Center which is just one of many Buddhist and Zen meditation groups in town. Additionally, there're Jewish Reform synagogues, Conservative Jewish temples, Orthodox and Reconstructionist communities. A mosque is in the works and store-front churches of all denominations crop up on every corner. There's not one but two Mennonite communities in Evanston, a Unitarian Universalist Congregation and a Quaker meetinghouse.
Evanston might still be the City of Churches and it's a wonderful city at that – but there is also a rich multi-faith community developing here and I could not be more pleased. As Diana Eck and her Pluralism Project can attest, Evanston is hardly unique in this respect. The religious landscape of the U.S. is ever-changing and becoming more diverse than we have ever before known it to be. But, it is up to us to create pluralism out of our rapidly increasing diversity. We have to turn a fact: "Evanston is religiously diverse" into an intentional mission that incorporates a desire to understand our neighbors and to utilize that understanding toward social justice goals. The first step is to arm yourself with the relational experience and the religious literacy to truly benefit from this new situation.
Throughout this month I have contacted, communicated with and attended worship with many of Evanston's diverse religious communities and I have to say that I was utterly unprepared for this undertaking. The unique richness of each service is almost too much to take in. From the sparse, contemplative Quaker Meetinghouse to the embodied Reba Place to Shabbat at Beth Emet, there are so many differences in the way these people express their faith but I've noticed there is also a core emotion that unites them. Each community has heartily welcomed me to join them and offered all the benefits and conveniences they possibly could. I keep feeling like each one is kinder than the last only to realize that it's simply impossible not to exceptionalize the radical hospitality each one shows me in that moment. I really wish other people would try something like this because you really can't imagine how beneficial it is, even to an atheist like me. I only advise that instead of doing it in the marathon my strict journalism deadline requires, you take it at a manageable pace to truly reflect on the wonder that is religious diversity.
Last week our dinner topic was "Jesus: The Man, The Myth, the Legend." Since I am the person who often chooses the topics for our meetings I have to admit that I'm rarely caught off-guard by the direction a discussion goes but that Tuesday was different.
It was meant to be a discussion of Jesus across different faiths. In attendance that night we had Jewish students, Christian students, Muslim students, non-religious students and a Hare Krishna student. Even I was a bit surprised to learn that everyone had something to say about Jesus. And that something was uniformly positive.
I was shocked to discover that in the Quran, baby Jesus (pbuh) speaks to defend his mother's chastity, announce his future importance and predict his resurrection. In the Christian tradition Mary's chastity is announced and protected by the angel Gabriel whose message is then spread by her fiancé, Joseph. It seemed almost feminist to have the child whose legitimacy was in question defend his mother's honor as opposed to her husband.
I then learned that in the Hare Krishna tradition Jesus is considered a great guru whose example should be followed. I didn't know much about Hare Krishna's before some of their members got involved with our initiative but am quickly coming to see that the goals of these students align very well with the goals of the Northwestern Interfaith Initiative and the IFYC's Better Together Campaign.
And of course I got to provide insight I had from my bible studies and Christianity classes as to the Jesus I try to emulate in my life – the stories of the Sermon on the Mount (which many of the Muslims had never heard told before) and the story of Jesus' insistence on pacifism even at the time of his arrest. While I don't believe in Jesus' divinity I do my best to live my life by his example in many ways. These stories are some of the big reasons I do interfaith work so it was nice to share them with the people I do that work with.
While I certainly can't say I fully comprehend the entirety of Jesus: The Man, the Myth, the Legend I definitely think I benefited from hearing others' descriptions of him. I think something as big as Jesus requires a few second opinions and while you don't have to accept every story you hear as truth, it certainly never hurts to expand your knowledge of what other's believe and say.
Today's post was written by Julianna Nunez. Juli is a Christian who spent her spring break on a Habitat for Humanity trip in Des Moines, Iowa. Her Jewish boyfriend, Martin, and atheist best friend, Susan, were also on the trip and in this post, Juli reflects on that experience.
I've learned that there are certain expectations that come with being the non-Jewish girlfriend of a Jewish boy. I better be a good cook and Martin, my boyfriend, wants his children to be raised Jewish. My interests in Judaism stem back to when I was 13 years old, so I had no qualms about that. However, this would mean that I would have to convert, which can be a very long process. Nonetheless, I love my boyfriend very much and I would consider my possible conversion as an example of my love for him as well as an alternate way to express my love for God.
Over spring break, some of my friends and I went to Des Moines, Iowa, to participate with Habitat for Humanity. The group, to my knowledge, consisted of Jews, Christians, and Atheists. The topic of religion did not come up. One of the group members, Susan, is an Atheist and can be considered my best friend at Northwestern University. We all participated in Habitat for Humanity because we felt it was the right thing to do, not because we felt a religious obligation.
It was nice to spend time with Martin in a non-academic environment. I learned that I have better motor skills than him (at least when it comes to destroying stuff with a hammer and handling power tools), I learned that he will not always respond to my flirty-ness, I learned that he goes to bed at an ungodly hour, and I learned he has all the patience in the world for me.
While our religions are different and we come from different areas (I come from a city while Martin comes from a suburb), we do not let these differences come between us. Instead, we learn from each other. I enjoy learning Judaism from Martin and Martin enjoys hearing my stories about growing up in an urban area.
We do not share a religion, but we share our love.
And of course, after deciding that the floor was far too uncomfortable to sleep on while in Iowa, we shared a giant red beanbag.
Today is the 100th anniversary of International Women's Day, a day where women mobilize "to mark the economic, political and social achievements of women." This year the theme is Equal Access to Education. Northwestern University's nod to International Women's Day is a bake sale to raise money for the high school education of a Kenyan young woman named Dorcas Wairimu, 15.
The non-profit in the video below is not affiliated with the Women's Center's campaign but I thought IWD was a good time to shed light on the Maasai population and education issues in Kenya in general. The Maasai people are torn between settling in Kenya or Tanzania as those governments are encouraging them to do or to continue their age-old tradition of being semi-nomadic. Currently there is much debate between NGO's about how to best preserve the Maasai culture while improving the lives and living standards of the men, women and families in this nomadic and very patriarchal culture. This video presents one perspective
Why should religious people care about the Maasai discussion or International Women's Day in general?
I think every religious person would tell you that they have considered gender through the eyes of their religion. From hijab to dastar, circumcision to mikveh, many religious offer a gendered view of practice and ritual. In honor of International Women's Day I thought it would be cool if we considered a few religious feminist organizations and their exploration of gender and religion. Whether you celebrate your gender because of your religion or reject your religion because you think they're incompatible, please join me in further celebrating International Women's Day by considering the following links
The Jewish Orthodox Feminist Alliance's mission:
The mission of the Jewish Orthodox Feminist Alliance is to expand the spiritual, ritual, intellectual and political opportunities for women within the framework of halakha. We advocate meaningful participation and equality for women in family life, synagogues, houses of learning and Jewish communal organizations to the full extent possible within halakha. Our commitment is rooted in the belief that fulfilling this mission will enrich and uplift individual and communal life for all Jews.
The Mormon-Feminist group WAVE: Women Advocating for Voice and Equality's mission statement:
We will provide a safe place for women and men to discuss their struggles with accepted gender roles and disparities of gender equality in the LDS Church.
Chances are that as you're reading this people are marching in Times Square to protest the upcoming anti-terrorism hearings that are admittedly targeting Muslim-Americans to prevent "home-grown terrorism" and fight against the "radicalization of Muslim communities in the United States." I don't think there could be anything more apropos for my 21st birthday!
A New York rabbi decided enough was enough and contacted his friend Daisy Khan (who came to speak at NU as part of Islam Awareness Week) and they decided to organize the "Today, I am Muslim Too Rally." The rally is a model for how interfaith activism can be used to make a more just America.
Follow the excitement here and sign the petition to broaden the homeland security hearings beyond Muslim-Americans.
Today's guest post is by Jennie van den Boogaard about ECO, a Hillel initiative to make the campus greener.
I grew up in a small town in Florida with a population of about 6,000. Half of those were conservative evangelical Christians, and the rest were agnostics, mostly surfer-stoners. There was little diversity, and I was the token Jew my entire life. I could have assimilated easily into my Christian surroundings. After all, it is the dominant culture of America. But for some reason, I latched on to what made me different and loved it. So when I came to Northwestern, I jumped at the chance to become involved with the Jewish community here, especially at Hillel, which I have found to be the most open and welcoming place on campus.
Hillel in general is like a second home for me on campus, but where I really found my place was in one of its student groups: ECO. ECO (Environmental Campus Outreach) is one of three main undergraduate 'green' groups on campus. ECO effortlessly combines the two things I love most: Judaism and environmentalism. Judaism is much more than a religion; it is a way of life. And I have been taught my entire life that if I am going to a responsible Jewish adult, then I need to take care of the world around me, not just people, but what I eat, what I do, and what I use. I plan to honor my ancestors, my culture, and my religion by always looking out for nature and my people, which doesn't include just my fellow Jews, but all human beings.
ECO meets every Sunday at 1 PM at Hillel. We welcome people of all faiths or no faith, and half of our members are not Jewish. About a third of our efforts are aimed at making Hillel more sustainable physically and spiritually. Another third is to reach out to the whole student body and inspire Northwesterners to live a more sustainable life. And the last third is dedicated to our projects and initiatives, such as our campaign to reduce plastic bag consumption on campus, provide recycling for ink cartridges, batteries, CFLs, and plastic bags, and help to make the organic garden at Norris flourish.
If you're interested in learning more you can go to www.ecohillel.com or email me at email@example.com.


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Muslim Internationalism as the Last Utopia: Crisis of World Order, Islamophobia and Pan-Islamism
Event Description
The Islamicate Studies Working Group* at the University of Pittsburgh presents: Cemil Aydin, Professor of History, University of North Carolina – Chapel Hill
Prof. Aydin's interests focus on both Modern Middle Eastern History and Modern Asian history, with an emphasis on the international and intellectual histories of the Ottoman and Japanese Empires. He is particularly interested in historical processes that shape transnational racial and civilizational identities, such as Muslim, Asian, African. His research and publications offer new ways to understand the historical roots of the contemporary world order by describing the process of imperial era conflicts and decolonization, especially from the perspective of non-Western actors of the Muslim world and East Asia.
*The Islamicate Studies Working Group consists of faculty and staff at the University of Pittsburgh who are exploring the prospects of building an academic program for the study of the Muslim World. Its members come from the Dietrich School's departments of English; History; Linguistics; Religious Studies; and Sociology; as well as from the Law School; the School of Education; and staff members from the Library and Global Studies, and it incorporates visiting postdoctoral fellows faculty members.