Holloman Air Force Base

CLINICAL EXPERIENCE indicates that the restoration of motor function of adult patients with hemiplegia occurs in an almost standardized fashion. No matter how severely the patient is affected, he goes through a se quence of recovery stages, beginning with the well-known flaccid stage and proceeding through a number of stages characterized by spasticity. Then, if progress continues, spas ticity diminishes and may eventually disappear altogether, in which case a near normal motor control has been attained. A comparatively small number of patients reach such an ad vanced recovery stage.

Alzheimer's disease (AD) is the leading cause of dementia. The two histopathological markers of AD are amyloid plaques composed of the amyloid-β (Aβ) peptide, and neurofibrillary tangles of aggregated, abnormally hyperphosphorylated tau protein. The majority of AD cases are late-onset, after the age of 65, where a clear cause is still unknown. However, there are likely different multifactorial contributors including age, enviornment, biology and genetics which can increase risk for the disease. Genetic predisposition is considerable, with heritability estimates of 60-80%. Genetic factors such as rare variants of TREM2 (triggering receptor expressed on myeloid cells-2) strongly increase the risk of developing AD, confirming the role of microglia in AD pathogenesis. In the last 5 years, several studies have dissected the mechanisms by which TREM2, as well as its rare variants affect amyloid and tau pathologies and their consequences in both animal models and in human studies. In this review, we summarize increases in our understanding of the involvement of TREM2 and microglia in AD development that may open new therapeutic strategies targeting the immune system to influence AD pathogenesis.

Abstract Smithtown is an intelligent tutoring system designed to enhance an individual's scientific inquiry skills as well as to provide an environment for learning principles of basic microeconomics. It was hypothesized that computer instruction on applying effective interrogative skills (e.g., changing one variable at a time while holding all else constant) would ultimately lead to the acquisition of the specific subject matter. This paper presents an evaluation of Smithtown in two studies of individual differences in learning. Experiment 1, an exploratory study, demonstrated that Smithtown fared very well when compared to traditional instruction on economics and delineated the performance indicators which separated better from worse learners in this discovery environment. Experiment 2 extended the findings from the exploratory study using a large sample of subjects (N = 530) from a different population interacting with Smithtown and showed that the performance indicators relating to hypothesis generation and testing were the most predictive of successful learning in Smithtown, accounting for considerably more of the variance in our learning criterion than a measure of general intelligence. Overall, the system performed as expected. Tutoring on scientific inquiry skills resulted in increased knowledge of microeconomics. The differentiating behaviors between more and less successful subjects were in agreement with specific behaviors relating to individual differences found in general studies on problem solving and concept formation. From an instructional perspective, the behaviors we have denoted can serve as a focal point for relevant intervention studies. From a design perspective, findings from these studies suggest modifications to intelligent tutoring systems so they may be more like the individualized teaching systems they have the potential to be. Additional informationNotes on contributorsValerie J. Shute The authors wish to acknowledge the many persons whose contributions have been invaluable to this project: Bill Alley, Jeff Blais, Jeff Bonar, Ray Christal, Kathleen Katterman, Pat Kyllonen, Alan Lesgold, Kalyani Raghavan, Wes Regian, Paul Resnick, and Dan Woltz. A special note of gratitude must be extended to the creative and diligent programmers of Smithtown: Jamie Schultz and Audrey Peterson Support for the large‐scale testing and analyses of Smithtown was provided by the Learning Abilities Measurement Program (LAMP), part of the Air Force Human Resources Laboratory. The Center for the Study of Learning is funded by the Office of Educational Research and Improvement of the U.S. Department of Education. The opinions expressed do not necessarily reflect the position or policy of either AF‐HRL or OERI and no official endorsement should be inferred

To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease.

Although protection in animal models against intravenous challenges with simian immunodeficiency virus (SIV) has been reported, no previous vaccines have protected against a heterosexual route of infection. In this study, five of six macaques were protected against vaginal challenge when immunized with formalin-treated SIV in biodegradable microspheres by the intramuscular plus oral or plus intratracheal route. Oral immunization alone did not protect. After a second vaginal challenge, three of four intramuscularly primed and mucosally boosted macaques remained protected. The data suggest that protection against human immunodeficiency virus vaginal transmission could be provided by microsphere-based booster vaccines when used to immunize women who are systemically primed.

Vaccination continues to be the single most important and successful public health intervention, due to its prevention of morbidity and mortality from prevalent infectious diseases. Severe immunologically mediated reactions are rare and less common with the vaccine than the true infection. However, these events can cause public fearfulness and loss of confidence in the safety of vaccination. In this paper, we perform a systematic literature search and narrative review of immune-mediated vaccine adverse events and their known and proposed mechanisms, and outline directions for future research. Improving our knowledge base of severe immunologically mediated vaccine reactions and their management drives better vaccine safety and efficacy outcomes.

BACKGROUND: Addition of up to 15.0 g/d salt to the diet of chimpanzees caused large rises in blood pressure, which reversed when the added salt was removed. Effects of more modest alterations to sodium intakes in chimpanzees, akin to current efforts to lower sodium intakes in the human population, are unknown. METHODS AND RESULTS: Sodium intakes were altered among 17 chimpanzees in Franceville, Gabon, and 110 chimpanzees in Bastrop, Tex. In Gabon, chimpanzees had a biscuit diet of constant nutrient composition except that the sodium content was changed episodically over 3 years from 75 to 35 to 120 mmol/d. In Bastrop, animals were divided into 2 groups; 1 group continued on the standard diet of 250 mmol/d sodium for 2 years, and sodium intake was halved for the other group. Lower sodium intake was associated with lower systolic, diastolic, and mean arterial blood pressures in Gabon (2-tailed P<0.001, unadjusted and adjusted for age, sex, and baseline weight) and Bastrop (P<0.01, unadjusted; P=0.08 to 0.10, adjusted), with no threshold down to 35 mmol/d sodium. For systolic pressure, estimates were -12.7 mm Hg (95% confidence interval, -16.9 to -8.5, adjusted) per 100 mmol/d lower sodium in Gabon and -10.9 mm Hg (95% confidence interval, -18.9 to -2.9, unadjusted) and -5.7 mm Hg (95% confidence interval, -12.2 to 0.7, adjusted) for sodium intake lower by 122 mmol/d in Bastrop. Baseline systolic pressures higher by 10 mm Hg were associated with larger falls in systolic pressure by 4.3/2.9 mm Hg in Gabon/Bastrop per 100 mmol/d lower sodium. CONCLUSIONS: These findings from an essentially single-variable experiment in the species closest to Homo sapiens with high intakes of calcium and potassium support intensified public health efforts to lower sodium intake in the human population.

Eighteen male and eight female primates, representing five subhuman species, were inoculated urogenitally with Mycoplasma genitalium, a microorganism recovered from men with nongonococcal urethritis. Male rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys apparently were resistant. Female squirrel monkeys (Saimiri sciureus) and female tamarins (Saguinus mystax) exhibited low-level, genital-tract infections. Male chimpanzees (Pan troglodytes) developed an obvious genital-tract infection, with some shedding organisms for 21 weeks. M. genitalium was recovered from the blood of two of the male chimpanzees, usually when large numbers of organisms were in the urethra. Female chimpanzees generally shed organisms for 12-15 weeks. Most chimpanzees colonized with the organism exhibited increased numbers of polymorphonuclear leukocytes in the genital tract and developed a significant antibody response. The results offer substantial evidence for the pathogenicity of M. genitalium for the urogenital tract of higher primates and suggest the microorganism may have a role in human genital-tract infections.

Intraguild predation (IGP) is an extreme form of competition that involves a dominant predator (IG predator), a subordinate predator that is also a superior exploitative competitor (IG prey), and their shared prey. Theory predicts three possible equilibria, which parallel increasing resource enrichment: exclusion of the IG predator, stable coexistence, and exclusion of the IG prey. Here, we report on the existence of two concurrent states in a model carnivore system dominated by IGP. Using species occurrence data obtained from randomly distributed remote cameras, we modeled the probabilities of detection and occupancy of the kit fox ( Vulpes macrotis ) and its IG predator, the coyote ( Canis latrans ), at White Sands National Monument, New Mexico, USA, using a recently developed conditional two‐species occupancy model. Kit foxes persisted in habitats of low resource abundance, which could not support coyotes. Coexistence occurred in adjacent habitats of higher resource enrichment, with coyote occupancy strongly correlated with small mammal abundance. The odds of a coyote being present vs. absent in prey‐rich habitats was 332:1 (± 0.006; SE) whereas the odds of a coyote being present vs. absent in prey‐poor habitats was 1:4 (± 0.11); thus, coyotes were much more likely to be present in prey‐rich habitats. Kit foxes were more frequently photographed in prey‐poor habitats avoided by coyotes. The odds of kit foxes being present vs. absent at a site where coyotes were absent was 7.9:1 (± 0.082), which was greater than the odds of kit foxes being present vs. absent at a site where coyotes were present (2.2:1 ± 0.081). These findings indicate that kit foxes avoid coyotes, but that their adaptations to arid conditions enable them to exploit habitats unsuitable for coyotes. Consequently, the primary driver of this spatial separation is the inability of coyotes to use prey‐poor habitats, rather than kit fox avoidance of coyotes. Our results reveal the existence of concurrent IGP states within the same ecological community, which is consistent with theoretical predictions, and highlight the power of the conditional two‐species occupancy model to illuminate how the abundance of shared prey shapes the competitive dynamic in ecological systems dominated by IGP.

The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4+ and T8+ cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has no detectable adverse effect on the population of T4+ cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo.

Predator-prey interactions revealed by vertebrate trace fossils are extremely rare. We present footprint evidence from White Sands National Monument in New Mexico for the association of sloth and human trackways. Geologically, the sloth and human trackways were made contemporaneously, and the sloth trackways show evidence of evasion and defensive behavior when associated with human tracks. Behavioral inferences from these trackways indicate prey selection and suggest that humans were harassing, stalking, and/or hunting the now-extinct giant ground sloth in the terminal Pleistocene.

Substantial portions of the dorsal, and almost the entire posteroventral and anteroventral (Av) cochlear nuclei were aspirated unilaterally in a chimpanzee. Axonal degeneration was studied by the Fink-Heimer method. The greatest amount of degeneration was followed medially from the region of Av into the lateral part of the trapezoid body. Degeneration also coursed around the superior surface of the restiform body and was traced into the dorsal and intermediate acoustic striae. Within the superior olivary complex, degeneration was distributed to: the ipsilateral lateral superior olive; laterally and medially oriented dendrites of the ipsilateral and contralateral medial superior olivary nuclei respectively (some perisomatic degeneration also was present bilaterally); the contralateral medial trapezoid nucleus; retro-olivary and preolivary cell groups bilaterally. Abundant degeneration passed into the contralateral lateral lemniscus and was distributed largely to its ventral nucleus. The contralateral central nucleus of the inferior colliculus was a major site of termination of ascending second order auditory fibers. The caudal tip of the ipsilateral ventral nucleus of the lateral lemniscus received abundant degeneration, but this diminished rostrally. The ipsilateral inferior colliculus contained a moderate amount of degeneration. A fair number of degenerated second order auditory fibers ascended in the contralateral brachium of the inferior colliculus and were distributed both to the principle and magnocellular divisions of the medial geniculate body. This pathway appears to represent a phylogenetic advance in the brain of the great ape.

ABSTRACT Ten hospital corpsmen working the 11 p.m. to 7 a.m. shift were selected for a study of night workers. Each completed a questionnaire describing his experiences with night work, and each slept in the laboratory for several days, while continuous EEG recordings were made. Although the quantity and distribution of the EEG sleep stages was not greatly different from that found in night sleep periods, there were some irregularities in the progression of EEG patterns, particularly interruptions in Stage REM sleep. It appeared that Ss slept better, worked better, and felt better after several weeks of assignment to night shift work.

BACKGROUND AND PURPOSE: There have been conflicting views and evidence reported in the literature concerning differences in muscle torque-generating capacities between clinical ("plug-in") console devices whose power source is provided by an electrical outlet (60 Hz, alternating current-driven) and portable electrical muscle stimulators (smaller, battery-operated stimulators). The purpose of this study was to compare the torque-generating capacity of the quadriceps femoris muscle during neuromuscular electrical stimulation (NMES) between a clinical neuromuscular electrical stimulator (VersaStim 380) and a portable neuromuscular electrical stimulator (Empi 300PV). SUBJECTS: Forty volunteer subjects with no known knee, neurological, or cardiovascular pathology (22 male, 18 female) participated in the study. METHODS: All subjects were tested with the clinical and portable stimulators on 2 separate days. Peak isometric torque of the quadriceps femoris muscle was measured using a Biodex dynamometer. Peak isometric quadriceps femoris muscle torque achieved during NMES and the average quadriceps femoris muscle torque integral produced over 10 NMES contractions were measured for each stimulator. Subjects also rated the amount of pain they experienced during the 10 NMES contractions using a numeric pain scale. Paired t tests were used to compare mean differences in measured variables between stimulator conditions. RESULTS: There were no differences in the peak torque or numeric pain ratings during the electrically stimulated contractions between stimulator conditions. The Empi 300PV produced a greater average torque integral compared with the VersaStim 380 during 10 electrically stimulated contractions (Empi 300PV=988.6-/+330.4 N.m-s, Versastim 380=822.7-/+292.6 N.m-s). DISCUSSION AND CONCLUSION: The portable Empi 300PV stimulator produced comparable levels of average peak torque at comparable levels of discomfort to those produced by the VersaStim 380 clinical stimulator. The Empi 300PV maintained greater amounts of torque production during a 10-contraction training session compared with the VersaStim 380. Based on these data, we believe that the Empi 300PV has the potential to produce adequate levels of torque production for NMES quadriceps femoris muscle performance training. Further study is needed to determine the effectiveness of using the Empi 300PV for quadriceps femoris muscle performance training.

Sudden cardiac death (SCD), presumed secondary to fatal arrhythmias, is a common cause of mortality in captive chimpanzees at the Alamogordo Primate Facility. Over the 6-year period at the Alamogordo Primate Facility between 2001 and 2006, 13 animals were defined as sudden cardiac death (11 male and 2 female) on the basis of clinical presentation which was 38% of all deaths. All animals had annual physical exams, including electrocardiograms and serial blood pressures. Six of the 13 animals underwent a complete cardiac evaluation by a veterinary cardiologist and all six of these animals were diagnosed with various degrees of cardiomyopathy. Systemic hypertension was noted in two of the 13 cases and antemortem cardiac arrhythmias were seen in all 13 animals. Histological examination of the hearts revealed myocardial fibrosis in 12 chimpanzees. Most of the animals (10/13) that died of sudden cardiac death had cardiomegaly (increased heart weight/body weight ratio) and some degree of myocardial fibrosis noted. Additional data as well as serial diagnostic evaluations will be needed to identify the possible causes of sudden cardiac death in captive chimpanzees.

Abstract The objective of this study was to expand the data on menstrual cycle serum hormone patterns in female common chimpanzees, both in terms of the number of cycles analyzed and by the addition of data on testosterone levels. Samples were obtained from 11 unanesthetized animals trained for conscious blood withdrawal. LH, FSH, 17β‐estradiol (E 2 ), progesterone (P), and testosterone (T) were measured by radioimmunoassay, genital swelling was recorded, and menstrual blood was noted. Concurrent midcycle elevations in LH and FSH and luteal phase elevations in progesterone suggested that the cycles were ovulatory. Detumescence of genital swelling occurred about 3 days after the midcycle LH peak, 1 day after the luteal phase nadir in E 2 , and 1 day after P levels exceeded 5 ng/ml. These relationships provide further support for the use of genital swelling in monitoring progress of the menstrual cycle. The hormone patterns in the chimpanzees closely resembled those of the human females, but E 2 and T levels were higher. The levels of E 2 and T were higher and the midcycle elevation in T was broader in the chimpanzee than in gorillas and orangutans. This is of interest because E 2 and T are implicated in the regulation of mating, and chimpanzees mate over a greater portion of the cycle than the other apes. These data indicate the need for further study of hormonal contributions to the different patterns of mating in the great apes. They also support the use of the female common chimpanzee as a model for the human female in endocrine studies of the menstrual cycle.

Both in vivo and in vitro studies clearly demonstrate that cells of the mononuclear phagocyte lineage are major hosts for human immunodeficiency virus type 1 (HIV-1) replication. Presumably these cells play a key role in the pathogenesis of acquired immunodeficiency syndrome (AIDS). To further delineate the interactions between HIV-1 and host cells, the susceptibility and permissivity of normal human peripheral blood-derived monocyte/macrophages (M/M) and T lymphocytes, and neoplastic monocytoid and lymphoid cell lines to various HIV-1 isolates was assessed. The results suggest: (1) "fresh" isolates recovered from patients and propagated only in normal host cells exhibit a dual tropism for both M/M and T cells, regardless of their tissue of origin or the cell type from which they were isolated; (2) the repeated passage of an HIV-1 isolate through normal M/M does not generally result in the loss of the ability to infect normal T cells nor vice versa; (3) the majority of fresh HIV-1 isolates do not infect neoplastic cells of either origin, and those that do show no preference for monocytoid or lymphoid targets, regardless of their cell origin.

Human footprints at White Sands National Park, New Mexico, USA, reportedly date to between ~23,000 and 21,000 years ago according to radiocarbon dating of seeds from the aquatic plant Ruppia cirrhosa . These ages remain controversial because of potential old carbon reservoir effects that could compromise their accuracy. We present new calibrated 14 C ages of terrestrial pollen collected from the same stratigraphic horizons as those of the Ruppia seeds, along with optically stimulated luminescence ages of sediments from within the human footprint–bearing sequence, to evaluate the veracity of the seed ages. The results show that the chronologic framework originally established for the White Sands footprints is robust and reaffirm that humans were present in North America during the Last Glacial Maximum.

Changes in gonadotropins, progesterone, cortisol, DHA, and DHAS were monitored in 10 female rhesus monkeys (Days 20-23 of the menstrual cycle) subjected to cage restraint with or without ketamine anesthesia for successive venipunctures. All animals were bled without sedation for 2 hr at 30-min intervals. Then 4 of the animals were anesthetized with ketamine-HCl and bleedings in all animals were continued for an additional 2.5 hr. FSH and progesterone were not appreciably affected by either restraint technique. LH declined steadily for the duration of the bleedings (P less than 0.05). Serum levels of cortisol and the adrenal androgens increased twofold (P less than 0.05). Anesthesia with ketamine had no effect on any of the six variables when compared with saline controls. Cortisol and dehydroepiandrosterone (DHA) levels tended to plateau (P less than 0.01) after 2 hr in both treated and control groups. In contrast, dehydroepiandrosterone sulfate (DHAS) levels increased continuously throughout the entire study period. These data indicate that ketamine anesthesia does not alter endocrine responses to venipuncture when administered following cage restraint of conscious animals. These findings further confirm the difficulties in obtaining estimates of basal levels of hormones which are responsive to stress and suggest that the first sample may provide the best estimate.

This paper describes the differential GPS and signal simulator equipment, procedures, and simulated aircraft trajectories used to analyze carrier phase measurements in estimating velocities and 3D positions. A differential GPS simulator system was used to generate C/A-code, P-code, and carrier phase signals from segments of the actual GPS constellation. Two pairs of dual-frequency receivers from different manufacturers were tested. These units have the capability of tracking the P-code (L1/L2 for one of the receivers and L2 for the other). An aircraft trajectory with accelerations up to 5 g was simulated, and analysis is performed in terms of the resulting velocity errors and dynamics. Two methods for estimating the 3D velocities were tested, namely carrier phase with fixed-integer and real-number (float) ambiguities. Both raw Doppler measurements and a number of carrier-phase-derived Doppler measurements were tested. As a by-product, the 3D positions could also be determined using various carrier phase approaches. The estimated quantities were compared with the reference quantities known a priori to determine the performance of the receivers under the various conditions simulated.