RESUMEN
Human Machine Interfaces (HMIs) can provide critical support and improve daily task functionality for prosthesis users or social interaction for patients with locked-in syndrome using an assistive communication device. One goal in the development of sophisticated HMIs is to reduce the cognitive load (CL) they place on the user to promote the use of the technology. Electroencephalogram (EEG)-derived measures collected with wired wet-electrode systems have been used to assess CL in laboratory environments and have demonstrated acceptable test-retest reliability. Assessment of CL during real-world unconstrained HMI operation, however, requires the use of a wireless dry-electrode EEG system which provides easier electrode application and untethered movement. However, the test-retest reliability of wireless dry-electrode systems to quantify CL has not been explored. Ensuring the consistent capture of CL-related signals across multiple sessions is critical if these devices are to be used to assess how improvements in HMIs affect CL. Therefore, the current study used a wireless dry-electrode EEG system to compare Evoked Response Potential (ERP) features of a simple auditory oddball task to measure CL during two separate testing sessions a week apart. ERPs of 11 subjects were recorded while participants performed a virtual task at two difficulty levels. A significant correlation was found between the P300 component of the ERPs and subjective ratings of CL during both testing sessions. Furthermore, there was a statistically significant test-retest reliability for this same ERP feature and similar signal-to-noise ratios (SNRs) across sessions.Clinical Relevance- This is an initial step in validating wireless dry-electrode EEG systems to assess cognitive load across multiple sessions. The evidence presented is critical if dry-wireless EEG systems are to be used to identify aspects of HMIs that reduce CL in clinical and real-life environments. Assessing CL in unconstrained environments can better inform clinicians and technology developers in their design of future HMIs.
Asunto(s)
Electroencefalografía , Potenciales Evocados , Cognición , Electrodos , Humanos , Reproducibilidad de los ResultadosRESUMEN
Commercial myoelectric prostheses need to be accurate and clinically viable to be successful. This study proposed a simultaneous and proportional control scheme with frequency division technique (SPEC-FDT) to address limitations in current myoelectric prosthesis control, specifically to address non-stationaries such as contraction level variations and unintended activations. Twenty able-bodied participants (14 males and 6 females, age 23.4 ± 3.0) and four individuals with transradial amputations performed wrist movements (flexion/extension, rotations and combined movements) in two degrees-of freedom virtual tasks. The SPEC-FDT had a completion rate (CR)>90% for both control and clinical participants which was significantly higher than the conventional technique (CR=68%). Our results showed that SPEC-FDT is highly accurate for both able-bodied and clinical participants and provides a robust myoelectric control scheme allowing for increased prosthetic hand functions.
Asunto(s)
Miembros Artificiales , Mano , Amputación Quirúrgica , Electromiografía , Femenino , Humanos , Masculino , Articulación de la MuñecaRESUMEN
PURPOSE: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, 3, is metabolized by cytochrome P450 3A4 and glucuronidation. This study evaluated the effect of rifampin, a potent inducer of drug-metabolizing enzymes, on axitinib plasma pharmacokinetics. Equal numbers of Japanese and Caucasian subjects were enrolled to assess the potential differences in axitinib pharmacokinetics between the two ethnicities. METHODS: Forty healthy volunteers were randomized to receive 5 mg axitinib alone and with 600 mg rifampin. RESULTS: Rifampin expectedly decreased AUCinf and Cmax of axitinib (geometric mean reduced by 79 and 71%, respectively). However, differences in axitinib pharmacokinetics were not observed between Japanese and Caucasian subjects (geometric mean ratios for axitinib treatment alone for AUCinf and Cmax were 103 and 96%). CONCLUSIONS: The results support a common axitinib starting dose in both populations. Potent inducers of drug-metabolizing enzymes reduce axitinib exposure and dose adjustments may be needed for optimal efficacy.
Asunto(s)
Pueblo Asiatico , Imidazoles/farmacocinética , Indazoles/farmacocinética , Rifampin/farmacología , Población Blanca , Adulto , Área Bajo la Curva , Axitinib , Estudios Cruzados , Citocromo P-450 CYP3A/metabolismo , Inhibidores Enzimáticos/farmacología , Genotipo , Glucuronosiltransferasa/genética , Humanos , Imidazoles/sangre , Indazoles/sangre , Japón , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Adulto JovenRESUMEN
The enhancement of an existing myoelectric control system has been investigated. The original one-channel system used an artificial neural network to classify myoelectric patterns. This research shows that a two-channel control system can improve the classification accuracy of the pattern classifier significantly, thus improving the reliability of the prosthesis.
Asunto(s)
Miembros Artificiales/instrumentación , Contracción Muscular/fisiología , Redes Neurales de la Computación , Procesamiento de Señales Asistido por Computador , Adulto , Biónica , Electrodos , Retroalimentación , Femenino , Humanos , Masculino , Diseño de Prótesis , Reproducibilidad de los ResultadosRESUMEN
The effect of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) on in vitro proliferation of lymphocytes to Candida antigens and lectins was examined in naive CBA/J mice and in similar mice colonized with Candida albicans by intragastric (i.g.) intubation and/or inoculated intradermally (i.d.) with the fungus. Lymph node lymphocyte and splenic lymphocyte (splenocyte) responses to soluble cytoplasmic substances derived from C. albicans varied with the route of inoculation of the fungus, the sex of the animal, and the presence or absence of rMuIFN-gamma treatment. In the absence of rMuIFN-gamma treatment, lymphoid cells from lymph nodes draining the site of the i.d. lesion responded well to soluble cytoplasmic substances. Colonization of the gut of female mice with C. albicans either had no effect or promoted better lymph node responses when such animals were also challenged i.d., whereas gut colonization of males followed by i.d. challenge appeared to have a suppressive influence on the level of proliferation in response to antigens in vitro. Antigen-specific splenocyte responses could be detected as well, and they were best in animals inoculated i.g.-i.d. or i.d. only. With the exception of lymph node lymphocytes from male mice, treatment of infected animals, regardless of the route of infection, with rMuIFN-gamma frequently resulted in lowered responses to antigens when comparable treatment groups were examined. With respect to mitogen stimulation, infection with C. albicans, especially i.g. or i.g.-i.d., resulted in a population of lymph node lymphocytes with lower-than-normal responses to concanavalin A but higher-than-normal responses to lipopolysaccharide (LPS). Splenocyte responses to mitogens were not altered as dramatically as the responses of lymph node lymphocytes, but splenocytes from female mice had a suppressed response regardless of the route of exposure to C. albicans, and those from mice which were maximally stimulated with C. albicans, i.e., inoculated i.g.-i.d., also had a suppressed response to concanavalin A. Treatment with rMuIFN-gamma either had no effect on the subsequent splenocyte responses or boosted subnormal mitogen responses toward the normal range. Collectively, these data illustrate that exposure to both C. albicans and rMuIFN-gamma influenced the responses to mitogen and C. albicans antigen of lymph node lymphocyte and splenocyte populations, as detected in vitro by lymphoproliferation. Treatment with rMuIFN-gamma often resulted in increased responsiveness to a B cell mitogen, LPS, and decreased responsiveness to a C. albicans antigen.
Asunto(s)
Candida albicans/inmunología , Interferón gamma/farmacología , Activación de Linfocitos , Animales , Concanavalina A , Femenino , Inmunización , Técnicas In Vitro , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos CBA , Proteínas RecombinantesRESUMEN
The cytokine tumor necrosis factor alpha (TNF-alpha) functions as an immunomodulatory protein and as a mediator of cachexia. We report that viable or Formalin-killed spherules of Coccidioides immitis induced the secretion of TNF-alpha by peritoneal-exudate cells from BALB/c mice. The identification of the cytokine as TNF-alpha was based on its lytic activity against the TNF-alpha-sensitive LS murine fibrosarcoma cell line but not the TNF-alpha-resistant LR cell line, its neutralization by rabbit anti-TNF-alpha, and its secretion by peritoneal cells having characteristics of macrophages. The induction of TNF-alpha was to spherules and not to contaminating lipopolysaccharide (endotoxin), as evidenced by the finding that polymyxin B, a reagent that blocks the TNF-alpha-inducing component of lipopolysaccharide, did not negate the production of TNF-alpha in response to spherules, whereas pretreatment of spherules with hyperimmune goat antiserum to spherulin neutralized the induction of TNF-alpha by these cells. The demonstration that C. immitis activates macrophages to secrete TNF-alpha in vitro is a new finding and warrants studies to determine whether this cytokine is produced during active coccidioidomycosis.
Asunto(s)
Antígenos Fúngicos/inmunología , Coccidioides/inmunología , Coccidioidina/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Anticuerpos Antifúngicos/fisiología , Líquido Ascítico/metabolismo , Femenino , Cabras , Sueros Inmunes/farmacología , Activación de Macrófagos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos BALB C , Polimixina B/farmacologíaRESUMEN
The immunologic effects of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) were determined in a murine model of candidiasis. Naive mice were given graded doses of rMuIFN-gamma and then challenged intravenously with Candida albicans. Increased morbidity and mortality were noted in four different strains of mice, viz., BALB/c, A/J, Swiss Webster, and CBA/J, providing the mice had not been immunized with C. albicans before challenge. Quantitative culture of selected organs of Swiss Webster and CBA/J mice surviving treatment with rMuIFN-gamma revealed elevated numbers of C. albicans cells, particularly in the kidneys, but also in the liver, lungs, and spleen. The lungs, livers, and spleen of female CBA/J mice were more protected from increased multiplication of the fungus than were those of males of the same species or female Swiss Webster mice. On the basis of these initial findings, the effect of treatment with 5,000 U of rMuIFN-gamma on immune responses in a gastrointestinal model of candidiasis was determined. CBA/J mice that had been colonized with C. albicans as infants were boosted with a cutaneous inoculation of the fungus when 6 to 10 weeks old; development of delayed hypersensitivity (DH), antibodies, and protective responses was assayed at intervals thereafter. Daily treatment with rMuIFN-gamma (beginning 1 day before cutaneous inoculation) suppressed weak immune responses but had little effect on responses which were strong. For example, DH and anti-C. albicans antibody production were suppressed in animals colonized with C. albicans but not boosted by cutaneous inoculation, and DH was suppressed in uncolonized animals that had been inoculated once cutaneously with the fungus as well. There was no rMuIFN-gamma-induced suppressive effect of DH in mice which had been stimulated maximally with C. albicans, i.e., colonized animals that had been boosted cutaneously with the organisms. Collectively, these data indicate that naive mice or mice with minimal levels of anti-C. albicans sensitivity, females somewhat more so than males, were sensitive to suppressive effects of in vivo treatment with rMuIFN-gamma when challenged with C. albicans. In contrast, under conditions similar to those of humans, in whom underlying immunity to C. albicans is usually present, suppression of host responses to C. albicans was not observed in immunized mice in response to treatment with rMuIFN-gamma.
Asunto(s)
Antígenos Fúngicos/administración & dosificación , Candidiasis/inmunología , Inmunidad Innata/efectos de los fármacos , Interferón gamma/administración & dosificación , Animales , Anticuerpos Antifúngicos/biosíntesis , Especificidad de Anticuerpos/efectos de los fármacos , Antígenos Fúngicos/inmunología , Candidiasis/prevención & control , Femenino , Hipersensibilidad Tardía/inmunología , Inyecciones Intravenosas , Masculino , Ratones , Ratones Endogámicos A , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Proteínas RecombinantesRESUMEN
CBA/J mice were immunosuppressed by repeated administration of goat antibody specific for mu chain of immunoglobulin M (IgM) and tested for nonspecific and Candida albicans-specific immune responses. Immunosuppression was demonstrated by a dramatic reduction in the number of antibody-forming cells in the spleens of anti-mu-treated mice when immunized with sheep erythrocytes, by greatly reduced in vitro responsiveness of both spleen and lymph node lymphocytes from anti-mu-treated mice to lipopolysaccharide, and by a large reduction in the number of splenic IgM-positive cells. T cell function, on the other hand, appeared to be relatively unaltered in anti-mu-treated animals, in the cytotoxic T lymphocyte activity against an allogeneic target was similar in splenocyte cultures from anti-mu- and mock-treated animals, and splenic and lymph node lymphocytes proliferated in response to concanavalin A in a lymphocyte stimulation assay. Moreover, Candida-specific delayed hypersensitivity to two different Candida antigens, one cell wall-derived (GP) and the other cell membrane-derived (BEX), was of comparable intensity in immunosuppressed and normal animals. When anti-mu- and mock-treated mice were immunized by the cutaneous inoculation of viable C. albicans blastospores and then challenged intravenously to assess the development of protective immunity, only mock-treated animals, male and female, had significant (p less than or equal to 0.05) protective responses demonstrable by reduction in the number of colony-forming units cultured from their kidneys 28 days after intravenous challenge. If consideration was given to the number of animals which had cleared Candida completely from the kidney, however, there appeared to be protective responses operative in the female anti-mu-treated animals as well. Neither anti-mu-treated males nor females, when immunized and challenged with C. albicans, produced Candida-specific antibody detectable by counterimmunoelectrophoresis, whereas all immunized and challenged mock-treated animals produced antibody. The data are consistent with the hypothesis that anti-mu treatment has little effect on multiple cellular immune functions, including those specific for C. albicans, and the combination of antibody, cell-mediated immunity and innate defenses are responsible for solid systemic defense against the fungus.