Showing papers by "United States Department of the Army published in 1997"

Clinical Recognition and Management of Patients Exposed to Biological Warfare Agents

Abstract: Concern regarding the use of biological agents—bacteria, viruses, or toxins—as tools of warfare or terrorism has led to measures to deter their use or, failing that, to deal with the consequences. Unlike chemical agents, which typically lead to violent disease syndromes within minutes at the site of exposure, diseases resulting from biological agents have incubation periods of days. Therefore, rather than a paramedic, it will likely be a physician who is first faced with evidence of the results of a biological attack. We provide here a primer on 10 classic biological warfare agents to increase the likelihood of their being considered in a differential diagnosis. Although the resultant diseases are rarely seen in many countries today, accepted diagnostic and epidemiologic principles apply; if the cause is identified quickly, appropriate therapy can be initiated and the impact of a terrorist attack greatly reduced.

Biological warfare : A historical perspective

Abstract: The deliberate use of microorganisms and toxins as weapons has been attempted throughout history. Biological warfare has evolved from the crude use of cadavers to contaminate water supplies to the development of specialized munitions for battlefield and covert use. The modern development of biological agents as weapons has paralleled advances in basic and applied microbiology. These include the identification of virulent pathogens suitable for aerosol delivery and industrial-scale fermentation processes to produce large quantities of pathogens and toxins. The history of biological warfare is difficult to assess because of a number of confounding factors. These include difficulties in verification of alleged or attempted biological attacks, the use of allegations of biological attacks for propaganda purposes, the paucity of pertinent microbiological or epidemiologic data, and the incidence of naturally occurring endemic or epidemic diseases during hostilities. Biological warfare has been renounced by 140 nations, primarily for strategic and other pragmatic reasons. International diplomatic efforts, including the 1972 Biological Weapons Convention, have not been entirely effective in preventing the enhancement and proliferation of offensive biological warfare programs. The threats posed by biological weapons are likely to continue into the future.

Acoustic monitoring system

Abstract: This invention is a transducer (14) in communication with fluid in a pad (12), held in close contact against a sound or movement (19) source which monitors acoustic signals transferred into the fluid (62). The signal pattern is monitored aurally and/or compared to predetermined reference patterns, and optional control and stimulation means can be activated in response to the comparison results. The sensed acoustic signal can be transmitted to a remote receiver or processed locally. Typically, the acoustic signal is representative of the heartbeat or breathing of a living organism. The monitoring system may be applied to diverse situations including SIDS, apnea, home baby monitoring, medical transport devices, blood pressure cuffs, seats, combat casualty care and hand-held devices.

Valuing urban wetlands: a property pricing approach

Abstract: This study estimates the value of wetland amenities in the Portland, Oregon, met- ropolitan area using the hedonic property price model. Residential housing and wetland data are used to relate the sales price of a property to structural characteristics, neighborhood attri- butes, and amenities of wetlands and other envi- ronmental characteristics. Measures of interest are distance to and size of wetlands, including distance to four different wetland types; open wa- ter, emergent vegetation, scrub-shrub, and for- ested. Other environmental variables include proximity to parks, lakes, streams, and rivers. Re- sults indicate that wetlands influence the value of residential property and that wetlands influence property values differently than other amenities. Increasing the size of the nearest wetland to a res- idence by one acre increased the residence's value by $24. Similarly, reducing the distance to the nearest wetland by 1,000 feet increased the value by $436. Home values were not influenced by wetland type. (JEL Q25)

Funding for malaria genome sequencing

Abstract: Sir — We should like to correct a statement in your Briefing on malaria about funding for the sequencing of the genome of the malaria parasite Plasmodium falciparum (Nature 386, 535–540; 1997). You report that the US Department of Defense, the US Burroughs Wellcome Fund, the UK Wellcome Trust and the US National Institutes of Health (NIH) have created a fund for this sequencing effort. In fact, no ‘fund’ has been established and there has been no pooling of funds among the donors. However, an exciting international consortium of scientists and funding agencies has been formed during the past year to provide the funds and reagents required to sequence the P. falciparum genome, and to produce, annotate and publish these sequences. We estimate that it will cost a minimum of $15 million to complete and annotate the 30-megabase P. falciparum genome. In the initial pilot phase, funding has been used to develop methods and to produce the reagents required for the high-throughput sequencing and for annotating the sequences. As a result of progress so far, the plan is to sequence the 14 chromosomes separately and to divide the work by chromosome, with about half the work being done in the United States and half in England. The work in the United States has initially been supported by grants from the NIH and the Burroughs Wellcome Fund and in England by the Wellcome Trust. Subsequent support will also be provided by the US Department of Defense. In the United States, the Naval Medical Research Institute is providing P. falciparum DNA and chromosomes, the Institute for Genomic Research will be doing a significant amount of the high-throughput sequencing and Stanford University is committed to sequencing at least one of the larger chromosomes. The donors are also supporting research on clone stability, library construction and optimization of sequencing reagents for the project at these three institutions, and at Roswell Park Cancer Institute and Harvard University. In England, the Institute of Molecular Medicine at the University of Oxford is providing P. falciparum reagents, and sequencing is being done at the Sanger Centre at Cambridge. It is expected that during the next few years a number of other laboratories may participate in the effort. The participants (scientists and donors) involved in this collaborative undertaking coordinate their activities through conference calls, e-mails and meetings. The researchers and funders met in Baltimore, Maryland, in December 1996 and will meet in Cambridge, England, on 16–17 June 1997. In addition, there has been an effort to involve the broader malaria community in this project and to facilitate widespread dissemination of the genomic information. There are substantial scientific obstacles to be overcome before the sequence of the P. falciparum genome is fully elucidated. Nonetheless, during the past year we have made great strides in identifying the funds required to pursue the project, building a strong group of scientists and institutions to execute the science, and establishing a collaborative network of scientists and donors. We believe that this project will provide a road map for malaria research in the twentyfirst century, research that will lead to improved treatment and prevention of a parasitic infection that causes hundreds of millions of illnesses, and millions of deaths annually. Stephen L. Hoffman Malaria Program, Naval Medical Research Institute, Bethesda, Maryland 20889-5607, USA e-mail: hoffmans@nmripo.nmri.nnmc.navy.mil William H. Bancroft Military Infectious Disease Research Program, US Army Medical Research and Materiel Command, Frederick, Maryland 21703, USA Michael Gottlieb Stephanie L. James Parasitology and International Programs Branch, NIAID/NIH, Bethesda, Maryland 20892, USA Enriqueta C. Bond Burroughs Wellcome Fund, Morrisville, North Carolina 27560, USA John R. Stephenson Michael J. Morgan The Wellcome Trust, London NW1 2BE, UK correspondence

Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex

Abstract: The lymph node cortex is a critical site for encounter between recirculating T cells and their specific antigens. Due to its extreme plasticity, little is understood of the underlying functional unit of the lymph node cortex, the paracortical cord. The idealized paracortical cord (approximately 100 microns by 1000 microns) stretches from a medullary cord to the base of a B-cell follicle. In cross-section, a cord can be visualized as a set of nested cylinders consisting of spaces bounded by cells. The spaces are: i) the lumen of the high endothelial venule (HEV), ii) perivenular channels-narrow potential spaces (0.1 micron) tightly encircling the HEV, iii) corridors-broad spaces (10-15 microns) constituting the majority of the parenchyma, and iv) the cortical sinus. In addition to these spaces for cell traffic, the conduit (fifth space) is a special delivery system for the transit of soluble factors to the HEV and emigrating lymphocytes. The cellular barriers between these spaces are high endothelium, fibroblastic reticular cells, or sinus-lining cells. This review describes the spaces of the paracortical cord and their cellular boundaries, outlines the movement of cells and fluids through these spaces, and discusses how this anatomy affects the efficiency of surveillance by T cells.

Meanings of Environmental Terms

Abstract: Certain terms and expressions that relate to the environment are problematic in that they vary widely in usage within and between disciplines, and several have been used as synonyms. In an attempt to correct the problem and standardize usage, this paper defines or redefines 10 of the most common environmental terms. Two of these terms, natural environment and environmental change, are defined on the basis of what is meant by natural as reflected by common usage and dictionary entries. The three degradation terms, environmental degradation, land degradation, and soil degradation, are defined as any change or disturbance to the environment, land, or soil perceived to be deleterious or undesirable. A sixth term, soil regeneration, is defined as the reformation of degraded soil through biological, chemical, and/or physical agencies. The remaining four terms, environmental quality, air quality, soil quality, and water quality, are defined as measures of the condition or state of each relative to the requirements of one or more biotic species and/or to any human need or purpose.

Pulsed second-harmonic generation in nonlinear, one-dimensional, periodic structures

Abstract: We present a numerical study of second-harmonic (SH) generation in a one-dimensional, generic, photonic band-gap material that is doped with a nonlinear ${\ensuremath{\chi}}^{(2)}$ medium. We show that a 20-period, 12-\ensuremath{\mu}m structure can generate short SH pulses (similar in duration to pump pulses) whose energy and power levels may be 2--3 orders of magnitude larger than the energy and power levels produced by an equivalent length of a phase-matched, bulk medium. This phenomenon comes about as a result of the combination of high electromagnetic mode density of states, low group velocity, and spatial phase locking of the fields near the photonic band edge. The structure is designed so that the pump pulse is tuned near the first-order photonic band edge, and the SH signal is generated near the band edge of the second-order gap. This maximizes the density of available field modes for both the pump and SH field. Our results show that the ${\ensuremath{\chi}}^{(2)}$ response is effectively enhanced by several orders of magnitude. Therefore, mm- or cm-long, quasi-phase-matched devices could be replaced by these simple layered structures of only a few micrometers in length. This has important applications to high-energy lasers, Raman-type sources, and frequency up- and down-conversion schemes.

Adjuvant for transcutaneous immunization

Abstract: A transcutaneous immunization system delivers antigen to immune cells without perforation of the skin, and induces an immune response in an animal or human. The system uses an adjuvant, preferably an ADP-ribosylating exotoxin, to induce an antigen-specific immune response (e.g., humoral and/or cellular effectors) after transcutaneous application of a formulation containing antigen and adjuvant to intact skin of the animal or human. The efficiency of immunization may be enhanced by adding hydrating agents (e.g., liposomes), penetration enhancers, or occlusive dressings to the transcutaneous delivery system. This system may allow activation of Langerhans cells in the skin, migration of the Langerhans cells to lymph nodes, and antigen presentation.

Bloodstain Pattern Analysis: With an Introduction to Crime Scene Reconstruction, Second Edition

Abstract: Bloodstain pattern analysis helps establish events associated with violent crimes. It is a critical bridge between forensics and the definition of a precise crime reconstruction. The second edition of this bestselling book is thoroughly updated to employ recent protocols, including the application of scientific method, the use of flow charts, and the inter-relationship of crime scene analysis to criminal profiling. It provides more illustrations, including color photographs, and explains the use of computer programs to create demonstrative evidence for court.

Rhizosphere microbial populations in contaminated soils

Abstract: Rhizosphere microbial populations may increase bioremediation of soil contaminated with organic chemicals. A growth chamber study was conducted to evaluate rhizosphere microbial populations in contaminated and non-contaminated soil. Alfalfa (Medicago sativa L.) and alpine bluegrass (Poa alpina L.) were grown in soil containing a mixture of organic chemicals for 14 weeks. The equal millimolar mixture of hexadecane, (2,2-dimethyl-propyl)-benzene, cis-decahydronaphthalene (decalin), benzoic acid, phenanthrene, and pyrene was added at levels of 0 and 2000 mg/kg. Organic chemical degrader (OCD) populations were assessed by a Most-Probable-Number technique, and bacteria and fungi were enumerated by plate count methods. Different methods for expressing OCD rhizosphere populations were investigated to determine the effect it had on interpretation of the results. At 9 weeks, the OCD numbers were significantly higher in rhizosphere and contaminated soils than in bulk and non-contaminated soils, respectively. Alfalfa rhizosphere OCD levels were 4 × 107/g for contaminated and 6 × 106/g for non-contaminated soils. Bluegrass rhizosphere OCD levels were 1 × 107/g and 1 × 106/g in contaminated and non-contaminated soils, respectively. Selective enrichment of OCD populations was observed in contaminated rhizosphere soil. Higher numbers of OCD in contaminated rhizospheres suggest potential stimulation of bioremediation around plant roots.

Neurochemical mechanisms in soman-induced seizures.

Abstract: This study examined brain regional neurotransmitter level changes as a function of seizure duration following soman intoxication. Rats, implanted with cortical electrodes and pretreated with HI-6, received a convulsant dose of soman. At selected times after seizure onset the EEG recording electrodes were removed and the animal was killed. Spinal cord cholinesterase (ChE) activity was rapidly and maximally depressed, while brain acetylcholine (ACh) levels showed elevations as early as 3 min after soman treatment and reached significantly high levels at time of seizure onset. Norepinephrine (NE) levels decreased starting 5 min after seizure onset and continued to decline. Levels of dopamine (DA) and of its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were elevated as early as 5 min after seizure onset and thereafter. The brain levels of aspartate were markedly decreased at and after 20 min of seizures; levels of glutamate were depressed at 80 min in the cortex. Levels of gamma-aminobutyric acid (GABA) were significantly increased in the cortex starting at 20 min after seizure onset, and in the striatum and hippocampus at 80 min after onset. The levels of glutamine, glycine and taurine were not changed at any time studied. These findings are consistent with the notion that inhibition of ChE and elevation of ACh initiate the seizure process, resulting in secondary changes in DA turnover and release of NE, and later changes in excitatory (aspartate, glutamate) and inhibitory (GABA) amino acid transmitters.

An axenic amastigote system for drug screening.

Abstract: Currently available primary screens for selection of candidate antileishmanial compounds are not ideal. The choices include screens that are designed to closely reflect the situation in vivo but are labor-intensive and expensive (intracellular amastigotes and animal models) and screens that are designed to facilitate rapid testing of a large number of drugs but do not use the clinically relevant parasite stage (promastigote model). The advent of successful in vitro culture of axenic amastigotes permits the development of a primary screen which is quick and easy like the promastigote screen but still representative of the situation in vivo, since it uses the relevant parasite stage. We have established an axenic amastigote drug screening system using a Leishmania mexicana strain (strain M379). A comparison of the 50% inhibitory concentration (IC50) drug sensitivity profiles of M379 promastigotes, intracellular amastigotes, and axenic amastigotes for six clinically relevant antileishmanial drugs (sodium stibogluconate, meglumine antimoniate, pentamidine, paromomycin, amphotericin B, WR6026) showed that M379 axenic amastigotes are a good model for a primary drug screen. Promastigote and intracellular amastigote IC50s differed for four of the six drugs tested by threefold or more; axenic amastigote and intracellular amastigote IC50s differed by twofold for only one drug. This shows that the axenic amastigote susceptibility to clinically used reference drugs is comparable to the susceptibility of amastigotes in macrophages. These data also suggest that for the compounds tested, susceptibility is intrinsic to the parasite stage. This contradicts previous hypotheses that suggested that the activities of antimonial agents against intracellular amastigotes were solely a function of the macrophage.

Endoproteinase Activity of Type A Botulinum Neurotoxin: Substrate Requirements and Activation by Serum Albumin

Abstract: Type A botulinum neurotoxin, a zinc-dependent endoproteinase that selectively cleaves the neuronal protein SNAP-25, can also cleave relatively short peptides. We found that bovine and other serum albumins stimulated the type A-catalyzed hydrolysis of synthetic peptide substrates, through a direct effect on the kinetic constants of the reaction. Furthermore, with bovine serum albumin in the assays, the optimum substrate size was 16 residues (11 on the amino-terminal side of the cleavage site and 5 on the carboxy-terminal side). To further investigate the catalytic requirements of the neurotoxin, peptides were synthesized with various amino acid substitutions at the P5 through P5′ substrate sites. Changes at all of these locations affected values for both kcat and Km. Substitutions at the P2, P1′, and P2′ sites had more pronounced effects on hydrolysis rates than did substitutions at the P1 site. Enzyme–substrate interactions at the P3′ threonine probably involved the side-chain methyl group rather than the hydroxyl group. Replacing the P2′ alanine with leucine eliminated detectable hydrolysis, but not binding, since this peptide was an inhibitor. A negatively charged residue was preferred at P5, but not at P4. The data indicate that type A botulinum neurotoxin has an extended substrate recognition region and a requirement for arginine as the P1′ residue.

Aided and automatic target recognition based upon sensory inputs from image forming systems

Abstract: This paper systematically reviews 10 years of research that several Army Laboratories conducted in object recognition algorithms, processors, and evaluation techniques. In the military, object recognition is applied to the discrimination of military targets, ranging from human-aided to autonomous operations, and is called automatic target recognition (ATR). The research described here has been concentrated in human-aided target recognition applications, but some attention has been paid to automatic processes. Definitions and performance metrics that have been developed are described along with performance data showing the present state-of-the-art. The effects of signal-to-noise and clutter parameters are indicated in the data. Multisensor fusion and model-based algorithms are discussed as the latest techniques under consideration by the military research community. The results demonstrate that useful performance can be achieved, and tools are evolving to understand and improve the performance under real-world conditions. The referenced research strongly indicates the need for the development of image science, as described in the paper, to support the theoretical underpinnings of ATR.

Structure of the receptor binding fragment HC of tetanus neurotoxin.

Abstract: The 2.7 A structure of the tetanus neurotoxin receptor binding fragment Hc reveals a jelly-roll domain and a beta-trefoil domain. Hc retains the unique transport properties of the holotoxin and is capable of eliciting a protective immunological response against the full length holotoxin.

Tendon repair clip implant

Abstract: A tendon repair clip implant system for placement on the dorsal side of a cerated or torn tendon to allow active range of motion post tendon repair, comprises: first and second clips. Each clip comprises: (i) two serrated sections joined by integral connecting section; the serrated sections being urgeable together to provide opposing mating teeth connection by arculate bending longitudinally around an axis of the connecting section; ii) the repair clip further comprising two relatively flat surfaces adjoining the connecting section and having openings therein through which sutures may be threaded and drawn through a lacerated tendon to assist in holding said tendon together; the openings being centered between a plurality of spikes extending from undersides of the flat surfaces to function as tendon inserts to assist in holding the lacerated tendon together.

Medical applications of virtual reality

Abstract: Medical applications for virtual reality (VR) are just beginning to emerge. These include VR surgical simulators, telepresence surgery, complex medical database visualization, and rehabilitation. These applications are mediated through the computer interface and as such are the embodiment of VR as an integral part of the paradigm shift in the field of medicine. The Green Telepresence Surgery System consists of two components, the surgical workstation and remote worksite. At the remote site there is a 3-D camera system and responsive manipulators with sensory input. At the workstation there is a 3-D monitor and dexterous handles with force feedback. The VR surgical simulator is a stylized recreation of the human abdomen with several essential organs. Using a helmet mounted display and DataGloveTM, a person can learn anatomy from a new perspective by ‘flying’ inside and around the organs, or can practice surgical procedures with a scalpel and clamps. Database visualization creates 3-D images of complex medical data for new perspectives in analysis. Rehabilitation medicine permits impaired individuals to explore worlds not otherwise available to them, allows accurate assessment and therapy for their disabilities, and helps architects understand their critical needs in public or personal space. And to support these advanced technologies, the operating room and hospital of the future will be first designed and tested in virtual reality, bringing together the full power of the digital physician.

Tunable 7 12-microm optical parametric oscillator using a Cr,Er:YSGG laser to pump CdSe and ZnGeP(2) crystals.

Abstract: A CdSe optical parametric oscillator (OPO) pumped by a 2.79-mum , Cr, Er:YSGG laser yielded a 59% signal-plus-idler slope efficiency (eta), a total idler output of 1.2-2.4mJ between 8.5 and 12.3 mum , and an idler beam that was 2.2-2.5 times the diffraction limit. A ZnGeP(2) OPO operated with a lower threshold, eta = 29% , and a forward idler output of 0.7-2.4 mJ from 6.9 to 9.9 microm . The signal and idler bandwidths were typically 4 cm(-1) for each OPO.

Safety and efficacy of a mutagen-attenuated Rift Valley fever virus vaccine in cattle.

Abstract: OBJECTIVE To examine safety and efficacy of a mutagen attenuated Rift Valley fever virus (RVFV) vaccine (RVF MP-12) in cattle. ANIMALS 38 pregnant cows, 14 steers, and 10 lactating dairy cows. PROCEDURE Pregnant cows in their third, fifth, or eighth month of gestation were vaccinated (1 ml of RVF MP-12 containing 5 log10 plaque-forming units [PFU] of virus) and were monitored daily through parturition for signs of disease, viremia, and immunologic response. Additionally, 10 vaccinated pregnant cows were challenge inoculated with virulent RVFV at post-vaccination day (PVD) 30 and were monitored daily for untoward effects. Ten unvaccinated pregnant cows also were challenge inoculated with virulent RVFV and served as challenge controls. Vaccinated lactating dairy cows were monitored for viremia and virus shedding in the milk through PVD 14. Yearling steers were vaccinated to assess their immunologic response to various doses of vaccine and were challenge inoculated with virulent RVFV at PVD 28 to assess protection. RESULTS 10 of 38 (26.3%) cows vaccinated during pregnancy developed transient postvaccination viremia titer > or = 2.5 log10 PFU/ml of serum. All vaccinated cows delivered live, healthy calves that were RVFV seronegative at birth, but which quickly acquired colostral antibodies. Vaccinated cows and their fetuses were protected when challenge exposed with virulent RVFV at PVD 30, whereas unvaccinated pregnant cows inoculated with RVFV became febrile and viremic, and aborted. Vaccine virus was unsuccessfully sought from milk of lactating dairy cows after vaccination, suggesting that shedding of vaccine virus through milk should not be a concern. Steers, inoculated with tenfold escalating vaccine doses, beginning with 1.0 log10 PFU, were protected against virulent RVFV challenge exposure. CONCLUSIONS RVF MP-12 may be safe and efficacious for use in pregnant or lactating bovids, and a minimal dose of vaccine may provide suitable protection against viremia.

Heat strain models applicable for protective clothing systems: comparison of core temperature response

Abstract: Gonzalez, R. R., T. M. McLellan, W. R. Withey, S. K. Chang, and K. B. Pandolf. Heat strain models applicable for protective clothing systems: comparison of core temperature response.J. Appl. Physio...