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In Vivo Blood Pressure Sensor

A. Pillai and D. P. Nair

Introduction to Biosensors Final Report

ECE Dept., UMass Lowell,

Abstract

Blood pressure measurement is an important diagnostic tool for ailments like dizziness, cardiac arrest, strokes etc. Conventional methods, also called non-invasive methods are not accurate when it comes to real time measurement of blood pressure. Hence, there is an urgent need for in-vivo blood pressure sensors. The advantage of having an in-vivo sensor is that it is an attractive proposition for continuous blood pressure monitoring and hence avoiding long term biological effects. In this study, we began by reviewing existing in-vivo blood pressure sensors and then found out what were the drawbacks for these pressure sensors. We are also proposing two solutions to overcome the two problems that were affecting the performance of these sensors.

Keywords: Blood pressure, in-vivo, noise improvement, power dissipation

Introduction

Blood pushing against the walls of the arteries causes a force, when the blood is pumped by the heart. This is called Blood Pressure. Damage to the body can be caused in many ways if this pressure rises and stays overtime. Coronary heart disease, Heart failure, Kidney Failure and stroke are few of the symptoms of High blood Pressure (HBP) along with many other serious health conditions.

It has been found that 1 in 3 adults in United States has a medical condition caused by High Blood Pressure .Because HBP by itself shows no symptoms there is a good chance that a person can have the disease for a long time without knowing about it. And during this time of unawareness, the HBP can cause damage to the blood vessels, the Heart, kidneys and other vital organs of the body. Checking and maintaining blood pressure numbers is important, even when the person is feeling fine regardless of age and state of health. High blood pressure on the other hand needs treatment and may prevent further damage of the vital organs. Low blood pressure needs as much attention as high blood pressure, as it poses as many health risks as HBP.

One of the tricky things about BP is that it is never the same value. Activities like sleeping and relaxing bring down the Blood pressure levels. Similarly blood pressure is expected to rise when the person gets up or even gets excited, stressed out. or nervous. It is also high with levels of activeness. If the numbers of BP remain above normal level even during moderate levels of activity that is when there is a risk for health problems. Risk factors increase as the number increases above 120/80 mm Hg or drop below 120/800 mm Hg.

A condition called "Prehypertension" basically states that there is a good chance a person will end up having HBP unless steps are taken to prevent it . If a person is currently under treatment for HBP and show consistent readings in the normal range, the blood pressure is considered to be under control. However, you still have the condition. You should see your doctor and follow your treatment plan to keep your blood pressure under control. Your systolic and diastolic numbers may not be in the same blood pressure category. In this case, the more severe category is the one you're in. For example, Stage 2 HBP is when a person has a systolic number of 160 and a diastolic number of 80. If a person has systolic number is 120 and a diastolic number is 95, the condtion is called Stage 1 HBP. If the person has additional risk of having diabetes or chronic kidney disease, HBP is defined as 130/80 mmHg or higher. Children and teenagers exhibit different HBP numbers. Age is one main factor that influences HBP. Following a healthy lifestyle is usually the best solution to delay or prevent HBP

In some cases, besides age and lifestyle, other diseases maybe responsible for raising blood pressure. Problems such as chronic kidney disease, sleep apnea, thyroid disease, may cause blood pressure to rise.. Medicines used to control certain diseases may also may raise a person’s blood pressure. Asthma medicines and cold-relief products are few of the examples.

Damages caused to the body when the blood pressure numbers stay high over a long time include the following:

• An abnormal larger or weaker heart, leading eventually to heart failure. This is a condition where in the heart cannot pump enough blood to meet the body's needs.

• An abnormal bulge in the wall of an artery is a medical condition called aneurysm .The main artery carries blood from the heart to the body; and these are the main spots for aneurisms to occur. The brain, legs, and intestines all have arteries and this might cause them to shut down. .

• Kidney failure may arise due to narrowing of the kidney vessels.

• Affecting the arteries by narrowing them which are responsible, this limits blood flow (especially to the heart, brain, kidneys, and legs). Causing medical conditions like heart attack, stroke, kidney failure, or amputation of part of the leg.

• Blood vessels in the eyes to burst or bleed. This may lead to vision changes or blindness.

When blood pressure is low, that is when another medical condition called Hypotension strikes. It happens mostly because the body cannot bring the pressure back to its normal level at all, or even fast enough. Low blood pressure sometimes occurs in some people all the time. This usually means there are no signs or symptoms that cause them any discomfort, and a low blood pressure s normal to them. In other people, certain conditions or factors cause abnormally low blood pressure. Less blood and oxygen flow to the body organs is the result of this. For the most part, hypotension is a medical concern only if it causes signs or symptoms or is linked to a serious condition, such as heart disease. Signs and symptoms of hypotension may include dizziness, fainting, cold and sweaty skin, fatigue (tiredness), blurred vision, or nausea (feeling sick to your stomach).

The signs and symptoms of orthostatic hypotension and neurallu mediated hypotension (NMH) are similar. They include:

• Dizziness or light-headedness

• Blurry vision

• Confusion

• Weakness

• Fatigue

• Nausea

When low blood volume (from major blood loss, for example) or poor pumping action in the heart (from conditions like heart failure, for example) causes shock:

• The skin becomes cold and sweaty. It often looks blue or pale. If pressed, the color returns to normal more slowly than usual. A bluish network of lines appears under the skin.

• The pulse becomes weak and rapid.

• The person begins to breathe very quickly.

These two medical conditions are reason enough why measuring blood pressure is important.

Conventional Methods of Blood Pressure Measurement

Noninvasive

Unlike invasive techniques non invasive techniques are less expensive and virtually have no complication at all. They are simpler and quicker, require less expertise and are least unpleasant and less painful for patients. Their biggest disadvantage however lies in the fact that these methods usually provide less accurate results with small differences in numerical values and also cannot be used for long term continuous monitoring.. Routine examinations and monitoring usually uses Non Invasive method of BP measurement.

Palpation

A minimum systolic value can be roughly estimated by palpation, most often used in emergency situations. Historically, students have been taught that palpation of a radial pulse indicates a minimum BP of 80 mmHg, a femoral pulse indicates at least 70 mmHg, and a carotid pulse indicates a minimum of 60 mmHg. However, at least one study indicated that this method often overestimates patients' systolic BP.

Auscultatory

The auscultatory method (from the Latin word for "listening") uses a stethoscope and a sphygmomanometer. This comprises an inflatable (Riva-Rocii) cuff placed around the upper arm at roughly the same vertical height as the heart, attached to a mercury or aneroid manometer. The mercury manometer, considered the gold standard, measures the height of a column of mercury, giving an absolute result without need for calibration and, consequently, not subject to the errors and drift of calibration which affect other methods. The use of mercury manometers is often required in clinical trials and for the clinical measurement of hypertension in high-risk patients, such as pregnant women. [pic]

Fig. 1: Auscultatory Method

Oscillometric

The oscillometric method was first demonstrated in 1876 and involves the observation of oscillations in the sphygmomanometer cuff pressure. which are caused by the oscillations of blood flow , i.e., the pulse.  The electronic version of this method is sometimes used in long-term measurements and general practice. It uses a sphygmomanometer cuff, like the auscultatory method, but with an electronic pressure sensor (transducer) to observe cuff pressure oscillations, electronics to automatically interpret them, and automatic inflation and deflation of the cuff. The pressure sensor should be calibrated periodically to maintain accuracy.

Oscillometric measurement requires less skill than the auscultatory technique and may be suitable for use by untrained staff and for automated patient home monitoring.

[pic]

Fig. 2: Mercury Manometer

Invasive

The most common techniques for monitoring blood pressure in small laboratory animals rely on using an invasive catheter-tip transducer inserted into an artery. Tonometry is a minimally invasive technique for a continuous measurement of pressure in blood vessels. The principle is that if a vessel is pressed against a flat surface of a pressure sensor diaphragm until vessel flattening occurs, according to Laplace’s law the pressure measured by the sensor will be equal to the pressure inside the vessel.

In Vivo Blood Pressure Measurement

In vivo (Latin for "within the living") is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro ("within the glass", i.e., in a test tube or petri dish) controlled environment. Animal testing and clinical trials are two forms of in vivo research. In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject.

Two types of In Vivo Blood pressure Measurement

1. Long-Term Implantable Blood Pressure Monitoring System

2. Wireless Battery less In VIVO Blood Pressure

Sensing Micro system

Long-Term Implantable Blood Pressure Monitoring System

The system employs an instrumented elastic cuff, wound around a blood vessel, operating in a linear “diameter v.s. pressure” region of the vessel for real time blood pressure monitoring. . The elastic cuff is made of silicone or latex rubber, filled with low viscosity bio-compatible insulating fluid with an immersed highly sensitive MEMS pressure sensor. The MEMS sensor enclosed in the cuff measures the pressure waveform, which represents a scaled version of the blood pressure in the vessel, independent of the cuff bias pressure exerting on the vessel. This method avoids vessel insertion, bleeding, and potential blood clotting. Furthermore, since the cuff is made of soft elastic material such as latex or silicone rubber, and the stiffness of the cuff can be much smaller than that of a blood vessel, the restrictive effect on the blood vessel is thus substantially minimized while the soft cuff is in close contact with the vessel. This can reduce the sliding-motion-induced signal drift, thus attractive for tolerating long-term implant variations and minimizing adverse biological effects.

Wireless Battery less In VIVO Blood Pressure Sensing Micro system

A proposed wireless less-invasive implantable blood pressure sensing microsystem is depicted in figure. The system employs an instrumented elastic circular cuff, wrapped around a blood vessel, to sense real-time blood pressure waveforms. The elastic circular cuff is made of bio-compatible elastomer and is filled with low viscosity bio-compatible insulating fluid, for example silicone oil, with an immersed MEMS pressure sensor and integrated electronic system. The MEMS sensor measures the pressure waveform in the cuff coupled from the expansion and contraction of the vessel.

The measured waveform represents a down-scaled version of the vessel blood pressure waveform and can be processed by a nearby integrated electronic system, consisting of a sensor interface circuitry, an analog-to-digital converter (ADC), and a system configuration and control unit for signal conditioning and coding, followed by a wireless data transmitter to an external transceiver. The overall electronic system architecture is shown in the figure below. An adaptive RF-DC power converter is incorporated in the system design to provide a sufficient and stable energy to the microsystem implanted in an un-tethered animal.

RF powering is used to eliminate the need of an implanted battery, thus substantially reducing the overall implant size and weight. A miniature RF coil, can be employed to receive an incoming RF energy to power the entire microsystem due to a low system power dissipation.

[pic]

Fig. 3 Wireless in-vivo sensor

The adaptive RF powering capability was enabled to provide a reliable power supply for the microsystem implanted in the freely moving laboratory mouse or rat. The measured digital blood pressure information was transmitted to a nearby external receiver by the on-chip FSK oscillator based transmitter.

The most common techniques for monitoring blood pressure in small laboratory animals rely on using an invasive catheter-tip transducer inserted into an artery. Tail cuff devices require animal restraint, thus resulting in a stress-induced signal distortion. Furthermore, tail cuffs can only obtain systolic and diastolic blood pressure levels instead of a continuous blood pressure waveform with detailed signatures, which are desirable for advanced biomedical research. Both technologies, therefore, are inadequate for real-time long-term monitoring. This is where wireless, batteryless long term implantable blood pressure monitor is desirable.

Microsystem Architecture

[pic]

Fig. 4 System architecture

The overall electronic system architecture is presented in Figure 4. An adaptive RF-DC power converter is incorporated in the system design to provide a sufficient and stable energy to the microsystem implanted in an un-tethered animal. RF powering is used to eliminate the need of an implanted battery, thus substantially reducing the overall implant size and weight. A miniature RF coil, can be employed to receive an incoming RF energy to power the entire microsystem due to a low system power dissipation.

Objectives

We found that there were two significant problems with the sensors that were specified in the background:

a) Increased noise levels

b) Very high power dissipation

A) Increased noise levels:

The measurement data after animal implant recovery exhibits an increased noise level, which is likely due to animal body vapor penetration through silicone coating to the capacitive MEMS pressure sensor and the electrical connections between the sensor and IC chip. The top electrode of the capacitive MEMS pressure sensor, which is implemented by a sensor diaphragm, is connected to the C/V converter summing node. This high impedance node can be highly sensitive to vapor penetration. Therefore, protection for moisture penetration is required for the sensor diaphragm as well as the electrical connections between the sensor diaphragm and IC chip.

[pic]

Fig. 5 Implementation of sensor inside a laboratory test subject

B) Very high power dissipation

An oscillator-based FSK transmitter was employed in the microsystem for data telemetry. The transmitter was on throughout the entire operation in the prototype design, dissipating an 80% of the system power.

Solutions proposed

A) For increased noise levels:

A passivation layer, such as silicon dioxide (SiO2 ) and silicon nitride (Si3N4 ), can be deposited on the top of diaphragm; and encapsulant material with strong moisture resistance can be used to protect the bond wires between the sensor and IC before applying silicone passivation layer. Improved packaging methods are, therefore, crucial to enhance the reliability of the micro system for long-term blood pressure monitoring.

B) For reduced power dissipation

To minimize the overall system power dissipation, a transmitter operating with a low duty cycle scheme and an increased transmission bandwidth can be designed. For example, the sampling frequency of the prototype system is 2 kHz with a data rate of 48 kbps, corresponding to a 24 bits data frame per 0.5 ms. The transmitter can be designed to be on for 0.05 ms for data transmission and off for the remaining 0.45 ms, resulting in one order of magnitude power reduction at an increased data rate of 480 kbps. This corresponds to a 72% overall system power reduction.

Timeline

[pic]

Since we were only two project members each one of us took one of the objectives. In the first four weeks of February we were researching in-vivo blood pressure sensors and were preparing for report 1. We did find a lot of unique conventional blood pressure sensors but not many were in vivo ones. However, in time for report one, we did find two in vivo blood pressure sensing mechanisms. But the second design had two problems that were listed above and we chose our objectives such that by first week of March we had the first objective ready. This was included in the first report. And the second objective was researched upon and it was proposed in the final report.

Conclusions

The objectives of this research have been successfully achieved. A cuff-based less-invasive blood pressure sensing technique was developed and demonstrated. This technique avoids vessel penetration and substantially minimizes vessel restriction due to the soft cuff elasticity, thus attractive for long-term implant. Wireless, batteryless, less-invasive, and implantable blood pressure sensing microsystems with data telemetry and adaptive RF powering capabilities for both laboratory rats and mice monitoring were designed and demonstrated.

The demonstrated wireless implantable technology will become an important research tool for system biology research. It is expected that the proposed sensing technique with microsystem engineering design will be desirable for future human-based health monitoring.

References:

1.  "Normal Blood Pressure Range Adults". Health and Life.

2.

3.  Klabunde, Richard (2005). Cardiovascular Physiology Concepts. Lippincott Williams & Wilkins. pp. 93–4. ISBN 978-0781750301.

4. Chobanian AV, Bakris GL, Black HR, et al (December 2003). "Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure".Hypertension 42 (6): 1206–52. doi:10.1161/01.HYP.0000107251.49515.c2. PMID 14656957.

5. "Diseases and conditions index - hypotension". National Heart Lung and Blood Institute. September 2008. Retrieved 2008-09-16.

6.  "Hypertension: management of hypertension in adults in primary care". NICE clinical guideline 34. London: National Institute for Health and Clinical Excellence (NICE). June 2006. Retrieved 2008-09-15.

7.  "Understanding blood pressure readings". American Heart Association. 11 January 2011. Retrieved 30 March 2011.

8.  Pesola GR, Pesola HR, Nelson MJ, Westfal RE (January 2001). "The normal difference in bilateral indirect BP recordings in normotensive individuals". American Journal of Emergency Medicine 19 (1): 43–5. doi:10.1053/ajem.2001.20021. PMID 11146017.

9.  Reckelhoff, Jane F (1 May 2001). "Gender differences in the regulation of blood pressure". Hypertension 37 (5): 1199–208. PMID 11358929.

10.  National Heart, Lung and Blood Institute. Blood pressure tables for children and adolescents. (Note that the median BP is given by the 50th percentile and hypertension is defined by the 95th percentilefor a given age, height, and gender.)

11.  (Pickering et al. 2005, p. 145) See Isolated Systolic Hypertension.

12.  "...more than half of all Americans aged 65 or older have hypertension." (Pickering et al. 2005, p. 144)

13.  Eguchi K, Yacoub M, Jhalani J, Gerin W, Schwartz JE, Pickering TG (February 2007). "Consistency of blood pressure differences between the left and right arms". Arch Intern Med 167 (4): 388–93.doi:10.1001/archinte.167.4.388. PMID 17325301.

14.  Agarwal R, Bunaye Z, Bekele DM (March 2008). "Prognostic significance of between-arm blood pressure differences". Hypertension 51 (3): 657–62. doi:10.1161/HYPERTENSIONAHA.107.104943.PMID 18212263.

15.  Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM (February 2006). "Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association".Hypertension 47 (2): 296–308. doi:10.1161/01.HYP.0000202568.01167.B6. PMID 16434724.

16. Mayo Clinic staff (2009-05-23). "Low blood pressure (hypotension) — Causes". . Mayo Foundation for Medical Education and Research. Retrieved 2010-10-19.

17. Rosenson RS, Wolff D, Green D, Boss AH, Kensey KR (February 2004). "Aspirin. Aspirin does not alter native blood viscosity". J. Thromb. Haemost. 2 (2): 340–1. PMID 14996003.

18.  Klabunde, RE (2007). "Cardiovascular Physiology Concepts - Mean Arterial Pressure". Retrieved 2008-09-29. Archived version 2009-10-03

19. Klabunde, RE (2007). "Cardiovascular Physiology Concepts - Pulse Pressure". Retrieved 2008-10-02. Archived version 2009-10-03

20. Markham LW, Knecht SK, Daniels SR, Mays WA, Khoury PR, Knilans TK (November 2004). "Development of exercise-induced arm-leg blood pressure gradient and abnormal arterial compliance in patients with repaired coarctation of the aorta". Am. J. Cardiol. 94 (9): 1200–2. doi:10.1016/j.amjcard.2004.07.097. PMID 15518624.

21.  Messerli FH, Williams B, Ritz E (2007). "Essential hypertension". Lancet 370 (9587): 591–603. doi:10.1016/S0140-6736(07)61299-9. PMID 17707755.

22. O'Rourke M (1 July 1995). "Mechanical principles in arterial disease". Hypertension 26 (1): 2–9. PMID 7607724.

23. Mitchell GF (2006). "Triangulating the peaks of arterial pressure". Hypertension 48 (4): 543–5. doi:10.1161/01.HYP.0000238325.41764.41. PMID 16940226.

24. Klabunde, RE (2007). "Cardiovascular Physiology Concepts - Arterial Baroreceptors". Retrieved 2008-09-09. Archived version 2009-10-03

25. Booth, J (1977). "A short history of blood pressure measurement". Proceedings of the Royal Society of Medicine 70 (11): 793–9. PMC 1543468. PMID 341169. Retrieved 2009-10-06.

26. "Vital Signs (Body Temperature, Pulse Rate, Respiration Rate, Blood Pressure)". OHSU Health Information. Oregon Health & Science University. Retrieved 2010-04-16.

27.  Deakin CD, Low JL (September 2000). "Accuracy of the advanced trauma life support guidelines for predicting systolic blood pressure using carotid, femoral, and radial pulses: observational study". BMJ321 (7262): 673–4. doi:10.1136/bmj.321.7262.673. PMC 27481. PMID 10987771.

28.  Interpretation - Blood Pressure - Vitals, University of Florida. Retrieved on 2008-03-18.

29. G8 Secondary Survey, "Manitoba". Retrieved on 2008-03-18.

30. (Pickering et al. 2005, p. 146) See Blood Pressure Measurement Methods.

31. (Pickering et al. 2005, p. 147) See The Oscillometric Technique.

32.  Laurent, P (2003-09-28). "Blood Pressure & Hypertension". Retrieved 2009-10-05.

33.  Elliot, Victoria Stagg (2007-06-11). "Blood pressure readings often unreliable". American Medical News (American Medical Association). Retrieved 2008-08-16.

34. Jhalani, Juhee; Tanya Goyal, Lynn Clemow, et al (2005). "Anxiety and outcome expectations predict the white-coat effect". Blood Pressure Monitoring 10 (6): 317–9. doi:10.1097/00126097-200512000-00006. PMID 16496447. Retrieved 2009-10-03.

35. (Pickering et al. 2005, p. 145) See White Coat Hypertension or Isolated Office Hypertension.

36.  (Pickering et al. 2005, p. 146) See Masked Hypertension or Isolated Ambulatory Hypertension.

37.  Mancia G, De Backer G, Dominiczak A, et al. (June 2007). "2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)". Eur Heart J 28 (12): 1462–536. doi:10.1093/eurheartj/ehm236. PMID 17562668.

38. Niiranen, TJ; Kantola IM, Vesalainen R, et al (2006). "A comparison of home measurement and ambulatory monitoring of blood pressure in the adjustment of antihypertensive treatment". Am J Hypertens19 (5): 468–74. doi:10.1016/j.amjhyper.2005.10.017. PMID 16647616.

39. Shimbo, Daichi; Thomas G. Pickering, Tanya M. Spruill, et al (2007). "Relative utility of home, ambulatory, and office blood pressures in the prediction of end-organ damage". Am J Hypertens 20 (5): 476–82. doi:10.1016/j.amjhyper.2006.12.011. PMC 1931502. PMID 17485006.[dead link]

40. National Heart, Lung and Blood Institute. Tips for having your blood pressure taken.

41. Table 30-1 in: Trudie A Goers; Washington University School of Medicine Department of Surgery; Klingensmith, Mary E; Li Ern Chen; Sean C Glasgow (2008). The Washington manual of surgery. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 0-7817-7447-0.

42.  Dugdale, David. "Blood Pressure". Retrieved 1 April 2011.

43. Klabunde, Richard. "Arterial Blood Pressure". Retrieved 31 March 2011.

44. Fung, Yuan-cheng (1997). Biomechanics:Circulation. New York: Springer. pp. 571. ISBN 038794383.

45.  Munson; Young, Okiishi, Huebsch (2009). Fundamentals of Fluid Mechanics (Sixth ed.). New Jersey: John Wiley &Sons, Inc.. pp. 725. ISBN 9780470262849.

46.  Womersley, J. R. (1955). "Method for The Calculation of Velocity, Rate of Flow and Viscous Drag in Arteries When The Pressure Gradient is Known". Journal of Physiology 127: 553–563.

47.  Sircar, Sabyasach (2008). Principles of Medical Physiology. India: vistasta Publishing. ISBN 978158890572.

48.  Fung, Yuan-cheng; Zweifach, B.W. (1971). "Microcirculation: Mechanics of Blood Flow in Capillaries". Annual Review of Fluid Mechanics 3: 189–210.

49.  What Is Pulmonary Hypertension? From Diseases and Conditions Index (DCI). National Heart, Lung, and Blood Institute. Last updated September 2008. Retrieved on 6 April 2009.

50. Chapter 41, page 210 in: Cardiology secrets By Olivia Vynn Adair Edition: 2, illustrated Published by Elsevier Health Sciences, 2001 ISBN 1560534206, 9781560534204

51.  Struijk PC, Mathews VJ, Loupas T, et al (October 2008). "Blood pressure estimation in the human fetal descending aorta". Ultrasound Obstet Gynecol 32 (5): 673–81. doi:10.1002/uog.6137.PMID 18816497.

52.  Sharon, S. M. & Emily, S. M.(2006). Foundations of Maternal-Newborn Nursing. (4th ed p.476). Philadelphia:Elsevier.

53. Textbook of Medical Physiology, 7th Ed., Guyton & Hall, Elsevier-Saunders, ISBN 0-7216-0240-1, page 220.

54. Gottdiener JS, Panza JA, St John Sutton M, Bannon P, Kushner H, Weissman NJ (July 2002). "Testing the test: The reliability of echocardiography in the sequential assessment of valvular regurgitation".American Heart Journal 144 (1): 115–21. doi:10.1067/mhj.2002.123139. PMID 12094197. Retrieved 2010-06-30.

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