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Appendix H Conclusions and Recommendations from the Workshop Report Emerging Technologies for Nutrition Research Submitted September 1997



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--> Appendix H Conclusions and Recommendations from the Workshop Report Emerging Technologies for Nutrition Research Submitted September 1997

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--> Committee Responses to Questions, Conclusions, and Recommendations As outlined in Chapter 1, the Committee on Military Nutrition Research (CMNR) was asked to provide a survey of newly available and emerging technologies that may be of significant value to the military for assessing and optimizing nutritional, physiological, and cognitive status and performance in military personnel. The following six categories of technologies were identified and evaluated for their applicability to the military mission: assessment of body composition, tracer techniques for study of metabolic processes, improved measures of energy expenditure and respiratory exchange, molecular and cellular approaches for evaluating nutritional requirements and status. assessment of immune status and function, and functional and behavioral measures of nutritional status. The Military Nutrition Division (MND) (currently the Military Nutrition and Biochemical Division) at the U.S. Army Research Institute of Environmental Medicine (USARIEM) posed six questions for the CMNR to aid in its evaluation of the techniques reviewed and its provision of guidance to MND concerning their applications to the military. In this chapter, the CMNR provides its answers to the questions posed by the Army, draws its conclusions on each of the six technologies reviewed, and makes its recommendations. The responses, conclusions, and recommendations were developed in discussion and prepared in executive session of the CMNR.

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--> Responses to Questions Posed by the Army This section is organized according to the six categories of technologies, with all of the Army's questions being answered under each technology. Techniques of Body Composition Assessment 1. Will the technologies be a significant improvement over current technologies? Anthropometric equations currently used by the military could be further refined with additional computer modeling, particularly with regard to their application to all ethnic groups. Computerized axial tomography (CAT) scanning, magnetic resonance imaging (MRI), and dual-energy x-ray absorptiometry (DXA) measurements can and have markedly improved compositional methodology in the clinic. These techniques could be used by the military to improve the accuracy and reliability of derived equations that use anthropometric measures to predict body fat content. Single-frequency bioelectrical impedance analysis (BIA) is not a reliable measure of body composition, but the methodology may be helpful in answering specific questions concerning hydration status. Multiple-frequency bioelectrical impedance spectroscopy may hold promise for compositional measurement in the future. 2. How likely are the technologies to mature sufficiently for practical use? Body composition (BC) methods are already quite mature, although multiple-frequency BIA requires some specific developmental work. The multifrequency method of BIA involves a simple and low-cost measurement system, but it is not sufficiently developed to provide accurate and reproducible estimates of changes in body composition. Its relative simplicity and low cost suggest that further development may be useful to see if current shortcomings can be overcome. At present, CAT scanning, MRI, and DXA provide reliable measures of composition but are expensive. CAT requires exposure to x rays, although some CAT scanners have been modified to reduce x-ray exposure, so this may no longer be a limitation. While all these techniques lack ease of use in the field, DXA at least appears to have the potential to serve as a new criterion measure to validate anthropometric equations.

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--> 3. What is the cost/benefit ratio of the new technologies, and how expensive (in both monetary and personnel terms) will they be to employ compared with the importance of the information they will provide? Anthropometric measurements and BIA are low cost and reasonably noninvasive (although a period of training is required to perform the former measurements accurately). The equipment required for CAT scanning, MRI, and DXA are high cost ($100,000–$1,000,000), and the training required to utilize the equipment is considerable. These costs, as well as the time required to perform the measurements on an individual, are a major limitation. Therefore, these techniques have value primarily as research tools (criterion measures) to aid in refining practical anthropometric methods for everyday use. 4. Are the technologies of such critical value that their development should be supported by Department of Defense (DoD) funds—such as can be provided by the Small Business Innovative Research (SBIR) program? Because fat-free mass (FFM) is the only BC component that appears to be correlated with physical performance capacity, technology is needed for the accurate estimation of muscle mass, lean body mass, or FFM. To assess the effects of military operations on body composition in individual soldiers, improvement is needed in methods for assessment and prediction of modest longitudinal changes in body composition. While DXA might provide the most accurate, direct longitudinal assessment, its relatively limited practicality in the field makes it a more likely candidate to be the criterion against which new anthropometric equations can be validated. Research with CAT, MRI, and DXA will continue in the private sector because of the medical applications of these technologies, including their potential to assess changes in body composition. Multifrequency BIA represents a simple technology that, if it could be developed sufficiently to overcome its current shortcomings, may be a technology whose adaptation for military field use could benefit from additional development funding. Anthropometric measurements may need additional support from computer development in the refinement of predictive equations. Such fine tuning of anthropometric methods is low cost and would likely be performed in-house or with limited outside support.

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--> 5. How practical are the technologies? Will they require dedicated personnel and complex, exotic equipment? Will the data provided be difficult to analyze? Anthropometric measurements and BIA are practical, although trained technicians should be utilized to perform these measurements. The large scanning devices are best used for developing predictive equations although mobile units are available. Cooperative work with medical or other institutions to utilize existing facilities and trained personnel appears to be the most practical and economical approach, as such facilities are experienced in collecting and analyzing data from these devices. 6. Can the technologies be used in the field (could they be used in the field or used to analyze samples collected in the field)? Anthropometric measurements can be conducted in the field. Although BIA also can be performed in the field, it currently does not represent an improvement over anthropometric measures of BC. Because the interpretation of BIA predictions of body composition is influenced significantly by environmental factors, health status, and physical activity, its use in the field may provide a mechanism for easily monitoring these factors, which are of significant interest to the military. Although mobile units are available for DXA and MRI, their use in the field to measure small changes in body composition is costly in terms of technician time. Hence, the use of these latter instruments is limited to validation of currently used anthropometric equations. Tracer Techniques for the Study of Metabolism 1. Will the technologies be a significant improvement over current technologies? Major advances in the understanding and measurement of metabolic processes have been made by incorporating these methodologies into studies of substrate utilization, energy requirements, and muscle function. The methods provide a safe mechanism for monitoring metabolites that was not available previously. 2. How likely are the technologies to mature sufficiently for practical use? Tracer methodology is developed and mature, although new labels, new techniques for separation of labeled metabolites (mass isotopomer distribution analysis), and more sensitive spectrometers are increasing its application. The

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--> doubly labeled water (DLW) technique has been used in field studies to estimate energy expenditure in troops. Other isotopic procedures have been used in laboratory settings to evaluate fuel use during exercise, and nuclear magnetic resonance (NMR) has been developed to assess intracellular metabolites and fuel stores. Reliable and reproducible data are best provided by laboratory groups with significant experience in the measurement and interpretation of the data obtained. 3. What is the cost/benefit ratio of the new technologies, and how expensive (in both monetary and personnel terms) will they be to employ compared with the importance of the information they will provide? Compounds labeled with stable isotopes are moderately expensive and the mass spectrometers required for analysis are expensive ($100,000–$300,000), but the cost of such measurements can be reduced with batch processing of labeled compounds and the use of core facilities. There is significant variation in the cost of studies utilizing this technology. When tracer isotopes can be administered and samples collected noninvasively in the field, cost is minimized. Samples and data can be analyzed in a core laboratory, and costs can be kept at a relatively low level for the value of the data obtained (an example being DLW studies of energy expenditure of troops in field operations). Incorporation of NMR or positron emission tomography (PET) greatly increases study expenses. When invasive techniques are required for administration and collection of samples, the stable isotope methods described are largely confined to laboratory use. However, for the information obtained using these stable isotope methods, the amount of data acquired is immense. NMR carries a large initial outlay for the magnet and the physicist to run it, but individual measurements are inexpensive to make, and the noninvasive nature increases its appeal. PET is prohibitively expensive ($2,000,000), and its use is limited to those facilities where sufficient medical need warrants its purchase. The information on metabolic processes that can be derived from this method is, as yet, untapped. 4. Are the technologies of such critical value that their development should be supported by DoD funds—such as can be provided by the SBIR program? The use of these techniques has developed in medical, nutrition, and physiology laboratories to improve the understanding of metabolic processes. It is a very active research field, heavily supported by federal funding. The MND

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--> should keep abreast of developments in the field to identify areas where the application to military nutrition is important. Funding for projects of specific interest to the military may be considered, but general funding is not necessary for this technology to develop rapidly. 5. How practical are the technologies? Will they require dedicated personnel and complex, exotic equipment? Will the data provided be difficult to analyze? Studies using stable isotopes require trained personnel for design and implementation. The technique is not trivial, nor is data analysis, so that experienced personnel are required to ensure meaningful results. Within that framework, the ease of the technique depends on the mode of dosing and sampling. Oral dosing followed by urine sampling is practical and easy for subjects. Intravenous dosing and arterial sampling require medical personnel and facilities. NMR and PET require little on the part of the subject, but highly trained personnel must run the equipment. 6. Can the technologies be used in the field (could they be used in the field or used to analyze samples collected in the field)? Studies involving invasive procedures to deliver isotope and collect samples are inappropriate for field work at this time. Studies that require magnets or cyclotrons cannot be performed easily in the field at this time. Ambulatory Techniques for Measurement of Energy Expenditure 1. Will the technologies be a significant improvement over current technologies? The DLW technique is a major improvement over the use of portable indirect calorimetry for estimating energy expenditure in the field. However, the use of ambulatory monitoring devices is an evolving technology that shows promise for use in estimating energy expenditure in the field as well. The application of near-infrared (NIR) spectroscopy, if perfected, could permit the noninvasive measurement of plasma metabolites, such as glucose, using a portable instrument with the accuracy and reliability of currently used blood-based methods. The difficulty in differentiating multiple metabolites in blood only may be overcome slowly.

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--> 2. How likely are the technologies to mature sufficiently for practical use? The measurement of total energy expenditure with doubly labeled water is already practical for field use. Activity monitoring remains a fertile field of investigation as newer methods of measuring activity and energy expenditure are integrated. NIR spectroscopy techniques and instrumentation are currently in use for routine food analysis and for blood flow monitoring of tissue oxygenation and are well developed. The measurement of a broad variety of other plasma metabolites, such as blood glucose, is an emerging technology that is not yet fully developed. Blood is a complex mixture of many organic compounds, each with overlapping spectra in the NIR range. In addition, blood flow is dynamic, and many plasma metabolites are in constant flux, particularly under conditions of stress. These represent formidable methodological obstacles not yet overcome, either by transcutaneous or reflectance NIR measurements. An additional obstacle is the unavailability, to date, of the portable equipment that would be required for field use. This is an area of considerable investigation. 3. What is the cost/benefit ratio of the new technologies, and how expensive (in both monetary and personnel terms) will they be to employ compared with the importance of the information they will provide? Doubly labeled water carries a fairly high price tag due to the costs of isotope (about $400–$500 per dose) and analysis (about $500 per dose). This cost is somewhat balanced by the ease of use, quantity of data produced, and safety of subjects. Portable oxygen consumption devices and ambulatory monitors are reasonably inexpensive and easy for subjects to use. Although the equipment that is required for portable, noninvasive testing of plasma metabolites using NIR spectroscopy would be relatively inexpensive to build and operate, the cost of development of that equipment could be great. 4. Are the technologies of such critical value that their development should be supported by DoD funds—such as can be provided by the SBIR program? The use of stable isotopes to measure energy expenditure is a well-developed method that requires no further support for development. Funds should continue to be appropriated to support the development of ambulatory monitoring, to refine the technology under development, and to validate the devices with field studies. The ''foot strike'' method is interesting and may be more useful if it can be applied to uneven terrain. This method is less expensive than iso-

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--> topic methods and could be applied readily to significant numbers of individuals in the field. The large potential market in the civilian sector for noninvasive, portable medical devices employing NIR spectroscopy for the measure of plasma metabolites should drive the development of suitable instrumentation. No investment should be required on the part of the military. 5. How practical are the technologies? Will they require dedicated personnel and complex, exotic equipment? Will the data provided be difficult to analyze? The DLW method for determination of energy expenditure is fairly practical to administer in the field, although interpretation is complicated by changes in water supply and large changes in activity patterns. Thus, analysis is sometimes problematic, and sample handling and data interpretation require trained personnel. Measures of oxygen consumption or ambulatory monitors are used more easily by individuals in the field but need further field testing. The data obtained are readily interpretable by computer analysis, but personnel who perform that interpretation require some training. Noninvasive field applications of NIR spectroscopy will require simple, rugged, and portable equipment, while routine health screening of military personnel at their home bases would have less stringent equipment requirements. However, at the present time, neither the technology nor the necessary instrumentation are available for either of these applications. 6. Can the technologies be used in the field (could they be used in the field or used to analyze samples collected in the field)? The performance of studies on energy expenditure in the field has a long history. The DLW technique has been widely used in the field and has yielded useful information in a variety of military studies. Studies of energy expenditure employing the DLW technique require oral dosing and urine sampling, and at present such studies are routinely conducted in the field; however, this method has only limited applicability due to cost. The foot strike method will benefit from more development and evaluation in a variety of field applications. When simple, rugged, and portable NIR spectroscopy equipment is developed to measure blood flow, tissue oxygen saturation, and a variety of plasma metabolites, it is possible to see many important field applications both in training and in other operations.

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--> Molecular and Cellular Approaches to Nutrition 1. Will the technologies be a significant improvement over current technologies? At the present time, the use of molecular cloning techniques to elucidate the human genome, study the control of gene expression, and control the synthesis of particular desirable or undesirable gene products both in vivo and in vitro is rapidly advancing the front and the pace of research in many areas. The techniques described represent the state of the art for most applications of molecular biology and are widely used in both academic and industrial research laboratories. In many respects, the use of isolated cell systems represents a significant advance over other methods (tissue culture and perfused organ systems, for example) for the study of cellular responses to external stimuli. The techniques await validation against appropriate in vivo measurements to demonstrate their true potential. 2. How likely are the technologies to mature sufficiently for practical use? Apart from the use of molecular cloning techniques to facilitate in vitro production of cellular products, such as vaccines, and improve the food supply, the most promising application for these technologies at the present time and in the near future is basic research. By bringing the investigation down to the level of gene expression, it is becoming possible to elucidate completely the mechanisms, by which stimuli, such as environmental stresses or changes in nutritional status, exert their influence upon physiological systems. Isolated cell techniques will find practical use largely, if not solely, in basic research settings. The likelihood that they will yield valid or useful information will depend on the effort that is expended to choose an appropriate model system and validate it property. With the exception of the use of red cell hemolysis to assess vitamin E status, the use of isolated cells for determination of nutritional status is not an available technology at this time. 3. What is the cost/benefit ratio of the new technologies, and how expensive (in both monetary and personnel terms) will they be to employ compared with the importance of the information they will provide? These are technical approaches that at the present time are almost exclusively limited in their application to the basic research setting. They require a considerable investment of capital for equipment and materials, time, and per-

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--> sonnel to develop a well-conceived research plan. While the information obtained by the use of molecular cloning techniques could not be obtained in any other way, the potential benefit of obtaining such information must be evaluated by anyone considering undertaking such research. Isolated cell approaches, in contrast, may be comparable in cost to molecular cloning techniques, yet the value of the information they can provide largely remains to be demonstrated (even within the scientific community). 4. Are the technologies of such critical value that their development should be supported by DoD funds—such as can be provided by the SBIR program? This technology is under active investigation in a variety of settings and supported by federal and private industry funding. Unless a specific application to a military setting is recognized, the CMNR does not recommend DoD funding at this time. At some point, as the technology develops, DoD may wish to evaluate whether its support would help a specific area, such as the effect of oxidative stress on gene expression, in view of the number of military settings where oxidative stress may be of particular concern. 5. How practical are the technologies? Will they require dedicated personnel and complex, exotic equipment? Will the data provided be difficult to analyze? At this time, techniques of molecular biology are not practical to answer nutritional questions of military significance. This type of work demands a considerable amount of equipment (although it is equipment that is currently available), extensive training, and the knowledge base to analyze the data. In addition, the development of the testing protocols alone for any product that emerges as a result of research conducted at the molecular biology level will require that a number of ethical and safety questions be taken into consideration. If isolated cell techniques can be validated sufficiently, it is conceivable that they might be utilized to study samples drawn from individuals working in the field and transported to a laboratory in a remote location. 6. Can the technologies be used in the field (could they be used in the field or used to analyze samples collected in the field)? While there is no reason to imagine conducting basic molecular biological or cell physiology research in the field, several field applications may become feasible in the future. One application that will become more appealing as the elucidation of the human genome progresses is the screening of cells taken from individuals recently exposed to extreme environmental conditions (stimuli) to

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--> determine the effects of these stimuli on gene expression. Such testing could be accomplished by sampling the tissues or cells of interest (if it can be done noninvasively) in the field setting and transporting them to a remote laboratory. Similar studies could be done to elucidate subcellular physiological processes using isolated cell approaches. A second application would involve techniques of gene transfer. These techniques, which are just now being developed and tested in humans who have been diagnosed with any of several rare genetic disorders or terminal cancers, may impart the ability to synthesize proteins not otherwise made by the body because of a missing or defective gene or some alteration in the regulatory process. The potential clearly exists to enhance the expression of particular genes or to place their expression under the control of nutrients (such as zinc) or some other dietary or environmental stimulus. Procedures of this sort await extensive testing, not to mention the solution of a myriad of ethical and practical questions, before realistic field applications can be considered. Assessment of Immune Function 1. Will the technologies be a significant improvement over current technologies? Improved methodologies for measuring functions of cell-mediated immunity and cytokine production are extensions of current methodologies. These generally are available in academic research institutions. Novel approaches to the development of oral vaccines for active immunizations, and human antibodies for passive immunization, represent vastly important improvements over current technologies and give great promise for inducing better and more complete immunity than do current vaccines, and at a far lower cost. 2. How likely are the technologies to mature sufficiently for practical use? Testing methodologies for evaluating immune system functions are constantly being studied and improved in academic centers. Whenever available, these improved methods will need to be adapted by military laboratories and modified for field use. Exciting new methodologies and approaches for the development of oral vaccines are being pursued vigorously by many groups, and the first human testing of experimental new vaccines should occur shortly. Since the Army is already highly engaged in the development of uniquely important military vac-

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--> cines, new technologies for vaccine development are of great potential importance. The possible creation of specific, human-compatible antibodies by the development and use of transgenic plants represents an important medical advance which could be of great value to military medicine. Such antibodies could be used to confer weeks to months of prophylactic passive immunity, or they could be used as specific forms of therapy. The transgenic antibodies would replace and expand the diversity of the available and costly passive immunization practices, which require the gathering and processing of human serum or the much more dangerous use of serum obtained form horses or other animals. 3. What is the cost/benefit ratio of the new technologies, and how expensive (in both monetary and personnel terms) will they be to employ compared with the importance of the information they will provide? The testing of immunological functions tends to be quite expensive, especially when these tests can only be done in research laboratories using costly reagents and equipment. Costs for field testing could be minimized (in terms of both money and loss of duty time by military personnel) if immunological studies could be limited to specific tests that prove to be most meaningful and reliable. Tests based on cytokine assays, especially those of the proinflammatory cytokines and related molecules excreted in urine, have great potential for adding important new diagnostic measures at a relatively inexpensive cost/benefit ratio. Costs of developing and testing potential new oral vaccines are likely to be comparable with those of conventional vaccines currently under development. However, oral vaccines have the potential for being far cheaper to produce (especially if effective antigens or antibodies can be produced in transgenic plants), and for being safer, more effective, and less costly to administer. 4. Are the technologies of such critical value that their development should be supported by DoD funds—such as can be provided by the SBIR program? The occurrence of immune system dysfunctions, such as those induced by one episode of Ranger training and those that may arise in the course of basic combat training or any military operation, needs to be investigated further. Such investigations should be extended to other operational situations that involve extreme physical stress and weight loss. In conducting these investigations, the DoD should employ the best available testing methodologies and adapt them to field use whenever necessary. Infectious diseases continue to have high DoD costs in terms of both medical care and lost time for military personnel. Infection-induced losses of body

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--> weight and essential nutrients can then impair physical performance for long periods of time. DoD use of immunizations to prevent (or minimize) the military impact of infectious diseases (including those due to biological warfare threat agents) has included the need for DoD funding and in-house research to develop, test, and procure all unique vaccines of military importance that are not available commercially. The potential for developing new families of oral vaccines that are more effective, less expensive, and easier to administer than currently available vaccines should not be ignored by the DoD. Creation of new families of transgenic plant-produced antibodies for passive protection against rare infections and toxemias of potential military importance represents a technological breakthrough that should be developed fully by the DoD in the immediate future. The CMNR supports the recommendation that a Science and Technology Objective be established for adaptation of militarily relevant vaccines for oral administration, and transgenic antibodies for passive protection, through the application of new technologies described in this report. 5. How practical are the technologies? Will they require dedicated personnel and complex, exotic equipment? Will the data provided be difficult to analyze? Advanced methodologies for a wide assortment of immunological assessments are already available in research laboratories, but considerable effort may be required to adapt them for field use. This problem can be minimized by focusing on a small, select number of tests that will yield the greatest amount of clinical information. Methodologies for developing a variety of effective new oral vaccines have already proven to be highly practical, and the first of such experimental vaccines are becoming available for human testing. Development and testing of new vaccines of unique military importance will still require time and money. The same is true for development of human antibodies in transgenic plants. 6. Can the technologies be used in the field (could they be used in the field or used to analyze samples collected in the field)? Field studies of Rangers in training have helped to highlight the immune dysfunctions that may be a consequence of these types of extreme environmental stress. Further such studies are needed to elucidate the nature and course of these immune system dysfunctions. Measurements of proinflammatory cytokines (such as IL-6 and IL-6 receptor antagonists) may be performed on single urine specimens collected in the field, although caution must be exercised in the interpretation of results. Further development of noninvasive assays (i.e., those that would use saliva, urine, stool, or other available samples), as well as simple,

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--> rugged, portable equipment for analyzing plasma metabolites and blood cell counts, should increase the ease of performing field measurements. Immunization is an important component of preparation for battlefield readiness. Refinement of vaccine production and improvement of delivery systems will greatly assist in increasing the effectiveness of, and compliance with, immunization programs. Functional and Behavioral Measures of Nutritional Status 1. Will the technologies be a significant improvement over current technologies? These methods actually constitute a group of technologies that measure different aspects of physical and cognitive performance. For one of these techniques, Muscle Function Analysis (MFA), the basic premises underlying the association between collected data and lean body mass or other indicators of nutritional status remains to be validated. The effects of prior strenuous physical exercise on MFA readings are not clear nor is it possible as yet to eliminate the contribution of voluntary muscle contraction or changes in activity of the sodium potassium pump. Furthermore, although the MFA procedure is relatively noninvasive, it is considered painful. This technique has the advantage of providing data in a very short time. Most of the methods of cognitive function assessment discussed in Chapters 24 and 25 represent the current state of the art. Some suggestions for new technologies, both those that were described in the chapters and those discussed during committee deliberations, were also considered. When miniaturization and interfaces are enhanced and portability is improved, such measures should have more field-relevant benefits for the military. 2. How likely are the technologies to mature sufficiently for practical use? It is believed that within the next 5 years, studies validating the use of MFA for assessment of nutritional status should be completed and documented in the peer-reviewed literature. The device currently is being tested in healthy individuals, trauma patients, hemodialysis patients, HIV+ patients, and nutritionally compromised individuals in general hospital wards, both before and after realimentation. In subjects studied to date, contractile characteristics of healthy volunteers appear reliable, and the test appears to be capable of measuring rapid changes in nutritionally compromised patients following the initiation of refeeding.

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--> Most of the cognitive assessment technologies discussed are already available. The inclusion of the ability to monitor or test cognitive function by incorporation of new technologies into existing equipment used by military personnel would be a significant step in nonintrusive testing. Such technologies should be readily available within 5 years, as required equipment is essentially available. Miniaturization may be required but should easily be developed. 3. What is the cost/benefit ratio of the new technologies, and how expensive (in both monetary and personnel terms) will they be to employ compared with the importance of the information they will provide? The MFA apparatus is relatively inexpensive, as is the cost for use. Skilled technicians are required to perform the measurements. With proper validation, the cost/benefit ratio for this technique would be quite low, although personnel must leave their assigned tasks to be tested. Some cognitive assessments, such as paper and pencil tests, are inexpensive but take personnel away from assigned tasks for short periods of time. Others, such as measures involving extensive computer hardware, other hardware (e.g., electroencephalogram monitors), or software programming, have high start-up costs for equipment but are designed to monitor, rather than to interfere with, the functions and operations of personnel. The information gathered could be valuable for assessing the role of nutritional and other factors, such as sleep in the field. The use of devices such as simulators involves expensive equipment and also takes personnel away from their tasks to complete the tests. 4. Are the technologies of such critical value that their development should be supported by DoD funds—such as can be provided by the SBIR program? Developments in the private sector need to be closely monitored by the DoD so that it may adapt what is already commercially available. Because most of the technologies are already developed, specific military field applications that involve miniaturization and increased portability should be financed by DoD. 5. How practical are the technologies? Will they require dedicated personnel and complex, exotic equipment? Will the data provided be difficult to analyze? The practicality of the MFA device is problematic at present. Constant monitoring does not appear to be possible at this time. In addition, subjects must

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--> interrupt their tasks to be measured. Although the device is light enough to be transported to the field, it is somewhat cumbersome for continuous wear and restricts arm movement. Nevertheless, the measurement is noninvasive and inexpensive. The total measurement time is only 10 to 15 minutes, results are available immediately, and in the future, continuous monitoring may be possible. The cognitive assessment technologies are already in use. Dedicated personnel needs are minimal except for data interpretation. The equipment is not complex or exotic, and most of it is already available. Analysis of these types of data has a long history, and few problems are anticipated; however, as with the MFA and many other assessment tools, personnel must leave their assigned tasks to participate in most tests of cognitive function. 6. Can the technologies be used in the field (could they be used in the field or used to analyze samples collected in the field)? At present, the potential for use of MFA in the field appears to be low. Although the device is light and relatively portable, the validity of the technique remains to be demonstrated, and its use is associated with causing significant pain to the subject. Field use should be reevaluated in the future after existing problems are overcome. The cognitive assessment techniques, with the exception of field simulators, are all applicable to field-testing scenarios. They await further improvements in miniaturization, portability, and durability. Committee Conclusions These conclusions were developed in executive session and represent the views of the CMNR. Methods of measuring body composition are relevant and important to the military to assure accuracy and fairness in the application of body composition measures to accession and retention of military personnel. Anthropometric measures are the most applicable methods for evaluating compliance with military standards of body fat. The more sophisticated technologies of CAT scanning, MRI, and DXA are useful tools for developing application equations from anthropometric measures to estimate body fat. BIA is a less-reliable method of measuring body fat at this time, but the methodology may be useful in answering specific questions concerning hydration state and function of cell membranes. Tracer methodology, particularly the use of stable isotopes, is an important technology for understanding and measuring metabolic processes (the doubly labeled water technique currently is used in studies of energy expenditure in

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--> the field and is a cost-effective technology for this purpose). Stable isotopes that can be administered and measured noninvasively through easily obtained samples offer important opportunities to estimate metabolic processes in the field. Central analysis of samples increases the practicality of their use in field studies. Ambulatory monitoring techniques, such as the foot strike measurement, also show good promise as field measures of work and energy expenditure. The various molecular and cellular technologies are interesting as research methods but are strictly laboratory research tools at present. Observing the development of these techniques and their application will be important for the MND at USARIEM, but investing in their in-house development is not recommended at this time. As questions develop that may be studied using these techniques, the DoD may wish to consider support for extramural research (for example, the effect of oxidative stress or malnutrition on gene expression). Studies of immune function are potentially very important to the military. An understanding of the effect of the various stresses of military operations on the body's immune function and how these may be modified to aid soldier performance is an important area for investigation. The development of vaccines that are effective against various infectious diseases of unique significance to the military population but not necessarily of significance to the civilian population may be very important in sustaining the ability of the soldier to operate effectively in the field. Oral vaccines may be most effective as they tend to mimic the route of exposure to the infectious agents that cause problems in the field. The development and production of human antibodies by transgenic plants create dramatic new possibilities for short-term (weeks-to-months) prophylaxis, or therapy, of unusual infectious diseases or toxemias of potential military importance and for which no other forms of immunization currently are available. The ability to study the cognitive performance of individuals while they perform their duties has great potential for improving soldier performance under stress. Current developments in computerized and miniaturized technology appear to permit expanded studies of real-time cognitive behavior. Support for the development of specific monitoring devices that are compatible with field military equipment may be necessary to implement this technology. Committee Recommendations The following recommendations are based on the CMNR's review and evaluation of the workshop discussions. Fair and equitable implementation of body fat and BMI standards is important to the military. It is recommended that continued research be carried out to refine the anthropometric measures using the sophisticated measurements of

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--> body composition provided by DXA, MRI, and/or CAT scanning to assure that measures used to evaluate personnel are equitable for gender, ethnic, and body type characteristics. The development and use of scanning technologies for the measurement of changes in body composition (particularly changes in muscle mass) that may result from field exercises should be refined in controlled laboratory environments and in collaboration with the civilian sector. Currently, multifrequency BIA is not sufficiently precise to be a useful tool for body composition determination. However, its potential as a simple field measure of hydrational status suggests that research to improve its value should be encouraged. Research by the private sector on the use of stable isotopes should be carefully monitored so that issues of concern to the military that can be studied effectively by these methods may be identified and the technology applied to the military situation when the costs versus the benefits are favorable. Since the effective application of this technology requires well-trained personnel and expensive and sophisticated equipment, the collaboration with other government and private sector laboratories in these studies continues to appear most expedient. In addition, as much information as possible should be obtained in well-controlled laboratory environments. The various molecular and cellular techniques for the study of nutrition and other physiological processes are strictly laboratory research tools at present and are not ready for implementation by the MND. Military problems that would appear to be amenable to investigation with these tools are of sufficiently broad interest as to be under consideration by established private-sector research laboratories. Maintaining awareness of the activities of these laboratories now receiving significant support by federal and industrial funds should continue, and therefore, DoD investment is not recommended at this time. Since military operations are frequently stressful and may be carried out in very hostile environments, it is important to understand the role that the body's immune function plays in helping the soldier cope and to consider ways in which immune responses may be controlled or enhanced to maximize the individual's ability to perform. Awareness of this research field and investment in selected research of potential significance to the military mission should be continued. The military must keep apprised of research findings on the influence of nutritional status on immune function. Research on possible vaccine programs that may protect soldiers from infectious diseases frequently encountered in military operations should be supported, particularly when the potential infections are not usually a problem in the civilian sector. Oral vaccine development should be encouraged. Preliminary research at U.S. Army Medical Research Institute for Infectious Diseases to develop militarily important oral vaccines should be expanded. Research should be initiated or funded to develop transgenic plants that can produce antibodies against infections or toxins of unique military importance and to assess the in-

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--> fluence of nutritional status on the response of military personnel to vaccinations. The development of techniques and equipment that would permit evaluation of cognitive performance of individuals while actually performing their operational tasks should be supported, with the caveat that such techniques must be validated and as much information gathered as possible in controlled laboratory environments prior to field testing. When special modification is required for use in military equipment, support should be given to such development (for example, miniaturization). The Committee on Military Nutrition Research is pleased to have participated with the Military Nutrition Division (currently the Military Nutrition and Biochemical Division), U.S. Army Research Institute of Environmental Medicine, and the U.S. Army Medical Research and Materiel Command in progress relating to the nutrition, performance, and health of U.S. military personnel. The CMNR hopes that this information will be valuable to the U.S. Department of Defense in developing programs that continue to improve the performance and lifelong health and well-being of service personnel.

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