Issues in development, evaluation, and use of the NASA Preflight Adaptation Trainer (PAT)

The Preflight Adaptation Trainer (PAT) is intended to reduce or alleviate space adaptation syndrome by providing opportunities for portions of that adaptation to occur under normal gravity conditions prior to space flight. Since the adaptation aspects of the PAT objectives involve modification not only of the behavior of the trainee, but also of sensiomotor skills which underly the behavioral generation, the defining of training objectives of the PAT utilizes four mechanisms: familiarization, demonstration, training and adaptation. These mechanisms serve as structural reference points for evaluation, drive the content and organization of the training procedures, and help to define the roles of the PAT instructors and operators. It was determined that three psychomotor properties are most critical for PAT evaluation: reliability; sensitivity; and relevance. It is cause for concern that the number of measures available to examine PAT effects exceed those that can be properly studied with the available sample sizes; special attention will be required in selection of the candidate measure set. The issues in PAT use and application within a training system context are addressed through linking the three training related mechanisms of familiarization, demonstration and training to the fourth mechanism, adaptation

Preliminary evaluation of a micro-based repeated measures testing system

A need exists for an automated performance test system to study the effects of various treatments which are of interest to the aerospace medical community, i.e., the effects of drugs and environmental stress. The ethics and pragmatics of such assessment demand that repeated measures in small groups of subjects be the customary research paradigm. Test stability, reliability-efficiency and factor structure take on extreme significance; in a program of study by the U.S. Navy, 80 percent of 150 tests failed to meet minimum metric requirements. The best is being programmed on a portable microprocessor and administered along with tests in their original formats in order to examine their metric properties in the computerized mode. Twenty subjects have been tested over four replications on a 6.0 minute computerized battery (six tests) and which compared with five paper and pencil marker tests. All tests achieved stability within the four test sessions, reliability-efficiencies were high (r greater than .707 for three minutes testing), and the computerized tests were largely comparable to the paper and pencil version from which they were derived. This computerized performance test system is portable, inexpensive and rugged

Surrogate measures: A proposed alternative in human factors assessment of operational measures of performance

Surrogate measures are proposed as an alternative to direct assessment of operational performance for purposes of screening agents who may have to work under unusual stresses or in exotic environments. Such measures are particularly proposed when the surrogate can be empirically validated against the operational criterion. The focus is on cognitive (or throughput) performances in humans as opposed to sensory (input) or motor (output) measures, but the methods should be applicable for development of batteries which will tap input/output functions. A menu of performance tasks is under development for implementation on a battery-operated portable microcomputer, with 21 tests currently available. The tasks are reliable and become stable in minimum amounts of time; appear sensitive to some agents; comprise constructs related to actual job tasks; and are easily administered in most environments. Implications for human factors engineering studies in environmental stress are discussed

Metagenomic-based Surveillance of Pacific Coast tick Dermacentor occidentalis Identifies Two Novel Bunyaviruses and an Emerging Human Ricksettsial Pathogen.

An increasing number of emerging tick-borne diseases has been reported in the United States since the 1970s. Using metagenomic next generation sequencing, we detected nucleic acid sequences from 2 novel viruses in the family Bunyaviridae and an emerging human rickettsial pathogen, Rickettsia philipii, in a population of the Pacific Coast tick, Dermacentor occidentalis in Mendocino County sampled annually from 2011 to 2014. A total of 250 adults of this human-biting, generalist tick were collected from contiguous chaparral and grassland habitats, and RNA from each individually extracted tick was deep sequenced to an average depth of 7.3 million reads. We detected a Francisella endosymbiont in 174 ticks (70%), and Rickettsia spp. in 19 ticks (8%); Rickettsia-infected ticks contained R. rhipicephali (16 of 250, 6.4%) or R. philipii (3 of 250,1.2%), the agent of eschar-associated febrile illness in humans. The genomes of 2 novel bunyaviruses (>99% complete) in the genera Nairovirus and Phlebovirus were also identified and found to be present in 20-91% of ticks, depending on the year of collection. The high prevalence of these bunyaviruses in sampled Dermacentor ticks suggests that they may be viral endosymbionts, although further studies are needed to determine whether they are infectious for vertebrate hosts, especially humans, and their potential role in tick ecology

Protected gates for topological quantum field theories

We study restrictions on locality-preserving unitary logical gates for topological quantum codes in two spatial dimensions. A locality-preserving operation is one which maps local operators to local operators --- for example, a constant-depth quantum circuit of geometrically local gates, or evolution for a constant time governed by a geometrically-local bounded-strength Hamiltonian. Locality-preserving logical gates of topological codes are intrinsically fault tolerant because spatially localized errors remain localized, and hence sufficiently dilute errors remain correctable. By invoking general properties of two-dimensional topological field theories, we find that the locality-preserving logical gates are severely limited for codes which admit non-abelian anyons; in particular, there are no locality-preserving logical gates on the torus or the sphere with M punctures if the braiding of anyons is computationally universal. Furthermore, for Ising anyons on the M-punctured sphere, locality-preserving gates must be elements of the logical Pauli group. We derive these results by relating logical gates of a topological code to automorphisms of the Verlinde algebra of the corresponding anyon model, and by requiring the logical gates to be compatible with basis changes in the logical Hilbert space arising from local F-moves and the mapping class group.Comment: 50 pages, many figures, v3: updated to match published versio

Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment.

Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b+ Ly6G+ neutrophils into the spinal cord. Targeting neutrophils resulted in a reduction in demyelination arguing for a role for these cells in myelin damage. Collectively, these findings emphasize that CXCL1-mediated attraction of neutrophils into the CNS augments demyelination suggesting that this signaling pathway may offer new targets for therapeutic intervention

Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416

Bimodules in bordered Heegaard Floer homology

Bordered Heegaard Floer homology is a three-manifold invariant which associates to a surface F an algebra A(F) and to a three-manifold Y with boundary identified with F a module over A(F). In this paper, we establish naturality properties of this invariant. Changing the diffeomorphism between F and the boundary of Y tensors the bordered invariant with a suitable bimodule over A(F). These bimodules give an action of a suitably based mapping class group on the category of modules over A(F). The Hochschild homology of such a bimodule is identified with the knot Floer homology of the associated open book decomposition. In the course of establishing these results, we also calculate the homology of A(F). We also prove a duality theorem relating the two versions of the 3-manifold invariant. Finally, in the case of a genus one surface, we calculate the mapping class group action explicitly. This completes the description of bordered Heegaard Floer homology for knot complements in terms of the knot Floer homology.Comment: 153 pages, 29 figures; v4: Address referee comment

Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass.

Aging reduces the number of mesenchymal stem cells (MSCs) that can differentiate into osteoblasts in the bone marrow, which leads to impairment of osteogenesis. However, if MSCs could be directed toward osteogenic differentiation, they could be a viable therapeutic option for bone regeneration. We have developed a method to direct MSCs to the bone surface by attaching a synthetic high-affinity and specific peptidomimetic ligand (LLP2A) against integrin α4β1 on the MSC surface to a bisphosphonate (alendronate, Ale) that has a high affinity for bone. LLP2A-Ale induced MSC migration and osteogenic differentiation in vitro. A single intravenous injection of LLP2A-Ale increased trabecular bone formation and bone mass in both xenotransplantation studies and in immunocompetent mice. Additionally, LLP2A-Ale prevented trabecular bone loss after peak bone acquisition was achieved or as a result of estrogen deficiency. These results provide proof of principle that LLP2A-Ale can direct MSCs to the bone to form new bone and increase bone strength