A Kinematic Approach to Understanding Performance in Upper-Extremity Function during a Goal-Directed Man-Machine Interface Task in a Submariner Environment.

In December of 2014, the United States Congress funded a fundamental shift in the recruiting policy of the US Navy Submarine Force to include the integration of women. As a result, design modifications became necessary, especially those that facilitate integration without inflating costs. Current cost levels associated with new submarine design(s) are maintained through the use of legacy components and systems. Additionally, many of the systems aboard are computer controlled, necessitating man-machine interfaces. As common practice, military activities that involve man-machine interfaces have always focused on the dexterity of the hands, often neglecting the role of movement in the task; therefore, there is a need to understand upper-extremity kinematics issues associated with man-machine interfaces. Joint kinematics of the right upper extremity of 10 subjects was measured using an optoelectronic motion capture system. Center of gravity displacements were measured using a force plate during touchscreen movement tasks paced by six different movement frequencies from a metronome (0, 1.0, 1.3, 1.7, 2.0, and 2.7 Hz). Results showed no significant difference in touch accuracy, task completion time, shoulder and elbow angular displacements, and shoulder and elbow flexion/extension velocity; however, a significant difference (0.002; p ≤ 0.05) in shoulder adduction/abduction velocity was observed. In arranging systems and components in submarine and surface vessel environments, consideration in not only providing a means of adjustability (e.g., height, proximity, and orientation) but in the dimensions of the systems and components themselves must also be considered based on the required operation.

Valproic acid adjunctive therapy for HIV-associated cognitive impairment: a first report.

In vitro and animal model data demonstrate that valproic acid (VPA) can ameliorate HIV-associated neurotoxicity. The authors conducted a pilot 10-week placebo-controlled study of VPA 250 mg twice daily in 22 HIV-infected individuals with (n = 16) and without (n = 6) cognitive impairment. VPA was safe and well tolerated, with trends toward improved neuropsychological performance and brain metabolism in the impaired subjects.

The ethics of research into schizophrenia prevention: a carer's perspective.

OBJECTIVE: To outline from a carer's/family's perspective the ethical concerns raised by research into screening for factors in people at risk of schizophrenia. METHOD: The need for families and carers of people with schizophrenia to seek a voice in the ethics of research into schizophrenia prevention is described. The possibility that societal myths, literature and language have created sustained ignorance about psychotic illnesses, resulting in fear and/or prejudice, is considered. The impact of these factors greatly exacerbating the burden of schizophrenia for sufferers and their families is discussed. RESULTS: There is evidence that people with schizophrenia share the disadvantages of other disempowered minorities. It is necessary for ethical constraints to be cognisant of this; research should include critically exploring reasons for attempting to eliminate the condition. CONCLUSIONS: Development of an ethical framework for prevention research into schizophrenia should include carer/family input. From a carer/family perspective, research into schizophrenia should be directed at ameliorating the effects of the illness by advancing methods of early diagnosis and by finding suitable treatments that do not carry punitive side-effects, thus allowing people with the illness to reach their potential in all aspects of their lives. Therapeutic relief combined with the elimination of social ostracism would greatly benefit people with schizophrenia and their families.

Monitoring, modelling and environmental exposure assessment of industrial chemicals in the aquatic environment.

Monitoring and laboratory data play integral roles alongside fate and exposure models in comprehensive risk assessments. The principle in the European Union Technical Guidance Documents for risk assessment is that measured data may take precedence over model results but only after they are judged to be of adequate reliability and to be representative of the particular environmental compartments to which they are applied. In practice, laboratory and field data are used to provide parameters for the models, while monitoring data are used to validate the models' predictions. Thus, comprehensive risk assessments require the integration of laboratory and monitoring data with the model predictions. However, this interplay is often overlooked. Discrepancies between the results of models and monitoring should be investigated in terms of the representativeness of both. Certainly, in the context of the EU risk assessment of existing chemicals, the specific requirements for monitoring data have not been adequately addressed. The resources required for environmental monitoring, both in terms of manpower and equipment, can be very significant. The design of monitoring programmes to optimise the use of resources and the use of models as a cost-effective alternative are increasing in importance. Generic considerations and criteria for the design of new monitoring programmes to generate representative quality data for the aquatic compartment are outlined and the criteria for the use of existing data are discussed. In particular, there is a need to improve the accessibility to data sets, to standardise the data sets, to promote communication and harmonisation of programmes and to incorporate the flexibility to change monitoring protocols to amend the chemicals under investigation in line with changing needs and priorities.

A risk assessment of selected phthalate esters in North American and Western European surface waters.

Potential risks to aquatic organisms by four commercial phthalate esters, dimethyl (DMP), diethyl (DEP), di-n-butyl (DBP), and butylbenzyl (BBP), were assessed using measured and calculated concentrations in North American and Western European surface waters. Predicted no effect concentrations (PNECs) were calculated using statistical extrapolation procedures and the large aquatic toxicity database. Surface water concentrations of DMP, DEP, DBP, and BBP were calculated using reported emissions to US surface waters from the toxics release inventory (TRI). Monitoring data obtained from the US EPA STORET database and literature surveys from North America and Western Europe show that DMP, DEP, DBP, and BBP are infrequently detected in surface water. Calculated and measured concentrations of DMP, DEP, DBP, and BBP are typically several orders of magnitude below their respective PNECs, indicating that these phthalate esters do not pose a ubiquitous threat to aquatic organisms in North American and Western European surface waters.

An 'inherent' biodegradability test for oil products: description and results of an international ring test. CONCAWE Biodegradation Task Force.

Current test guidelines for assessing 'inherent' (potential) biodegradability were designed for water-soluble, organic compounds of low volatility and are unsuitable for most oil products. It was against this background, that CONCAWE (the oil companies' European organisation for environment, health and safety) formed a task force to develop a standard test protocol for assessing the 'inherent' biodegradability of oil products.

Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development.

The role of fibrillin-1 in metanephrogenesis was investigated. Fibrillin-1 cDNA was isolated from the rat kidney cDNA library and sequenced, and its spatiotemporal expression was studied. It had approximately 88% homology with human fibrillin-1 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and an RGD binding site. Northern blot analysis revealed an approximately 10-kb transcript, and fibrillin-1 expression was developmentally regulated. In situ hybridization and immunofluorescence studies indicated that at day 15 of gestation, fibrillin-1 is expressed in the metanephric mesenchyme. At day 18, its expression was confined to nascent blood vessels and glomeruli, and it increased in the newborn and neonatal kidneys. Immunoprecipitation revealed an approximately 300-kDa band by SDS-PAGE. Treatment with fibrillin-1 antisense oligodeoxynucleotide induced marked dysmorphogenesis of the embryonic metanephroi. Concomitantly, the fibrillin-1 mRNA, antibody reactivity in the metanephroi, and fibrillin-1-specific radioincorporation were reduced. These data indicate that, like alphavbeta3 integrin, a known morphogen and a putative receptor of fibrillin-1, the fibrillin-1 modulates events related to early organogenesis and possibly also the vascularization of the rat kidney.

Relevance of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis.

Mammalian nephrogenesis begins by the reciprocal interaction of the ureteric bud with the undifferentiated mesenchyme. The mesenchyme differentiates into an epithelial phenotype with the development of the glomerulus and proximal and distal tubules. At the same time, the mesenchyme stimulates the branching morphogenesis of the ureteric bud that differentiates into the collecting ducts. These inductive interactions and differentiation events are modulated by a number of macromolecules, including the extracellular matrix (ECM), integrin receptors, and cell adhesion molecules. Many of these macromolecules exhibit spatiotemporal developmental regulation in the metanephros. Some are expressed in the mesenchyme, whereas others appear in the ureteric bud epithelia. The molecules expressed in the mesenchyme or at the epithelial:mesenchymal interface may serve as ligands while those in the epithelia serve as the receptors. In such a scenario the ligand and the receptor would be ideally suited for epithelial:mesenchymal paracrine/juxtacrine interactions that are also influenced by RGD sequences and Ca2+ binding domains of the ECM proteins and their receptors. This review addresses the role of such interactions in metanephric development.

Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal.

Glutamine and glutamate transport activities were measured in isolated luminal and abluminal plasma membrane vesicles derived from bovine brain endothelial cells. Facilitative systems for glutamine and glutamate were almost exclusively located in luminal-enriched membranes. The facilitative glutamine carrier was neither sensitive to 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid inhibition nor did it participate in accelerated amino acid exchange; it therefore appeared to be distinct from the neutral amino acid transport system L1. Two Na-dependent glutamine transporters were found in abluminal-enriched membranes: systems A and N. System N accounted for approximately 80% of Na-dependent glutamine transport at 100 microM. Abluminal-enriched membranes showed Na-dependent glutamate transport activity. The presence of 1) Na-dependent carriers capable of pumping glutamine and glutamate from brain into endothelial cells, 2) glutaminase within endothelial cells to hydrolyze glutamine to glutamate and ammonia, and 3) facilitative carriers for glutamine and glutamate at the luminal membrane may provide a mechanism for removing nitrogen and nitrogen-rich amino acids from brain.

Glucose transport by isolated plasma membranes of the bovine blood-brain barrier.

Luminal and abluminal endothelial plasma membrane vesicles were isolated from bovine cerebral microvessels, the site of the blood-brain barrier. Glucose transport across each membrane was measured using a rapid-filtration technique. Glucose transport into luminal vesicles occurred by a stereospecific energy-independent transporter [Michaelis-Menten constant (K(m)) = 10.3 +/- 2.8 (SE) mM and maximal velocity (Vmax) = 8.6 +/- 2.0 nmol.mg protein(-1).min-1]. Kinetic analysis of abluminal vesicles also showed a transport system with characteristics similar to the luminal transporter (K(m) = 12.5 +/- 2.3 mM and Vmax = 10.0 +/- 1.0 nmol.mg protein-1.min-1). These functional, facilitative glucose transporters were symmetrically distributed between the luminal and abluminal membrane domains, providing a mechanism for glucose movement between blood and brain. The studies also revealed a Na-dependent transporter on the abluminal membrane with a higher affinity and lower capacity than the facilitative transporters (K(m) = 130 +/- 20 microM and Vmax = 1.59 +/- 0.44 nmol.mg protein-1.min-1. The abluminal Na-dependent glucose transporter is in a position to transport glucose from the brain extracellular fluid into the endothelial cells of the blood-brain barrier. The functional significance of its presence there remains to be determined.

Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier.

Regulation of neutral amino acid transport was studied using isolated plasma membrane vesicles derived from the bovine blood-brain barrier. Neutral amino acids cross the blood-brain barrier by facilitative transport system L1, which may allow both desirable and undesirable amino acids to enter the brain. The sodium-dependent amino acid systems A and Bo,+ are located exclusively on abluminal membranes, in a position to pump unwanted amino acids out. gamma-Glutamyl transpeptidase, the first enzyme of the gamma-glutamyl cycle, is an integral protein of the luminal membrane of the blood-brain barrier. We demonstrate that oxoproline, an intracellular product of the gamma-glutamyl cycle, stimulates the sodium-dependent systems A and Bo,+ by 70 and 20%, respectively. Study of system A showed that 2 mM oxoproline increased the affinity for its specific substrate N-methylaminoisobutyrate by 50%. This relationship between the activity of the gamma-glutamyl cycle and system A transport may provide a short term regulatory mechanism by which the entry of potentially deleterious amino acids (i.e. neurotransmitters or their precursors) may be retarded and their removal from brain accelerated.

Gentamicin inhibits carrier-mediated dipeptide transport in kidney.

The effect of gentamicin on transport of pyroglutamylhistidine (pGlu-His) was examined in rabbit renal brush-border membrane vesicles (BBMV). Gentamicin, an aminoglycoside antibiotic, is limited in its usage because of nephrotoxicity characterized in part by transport defects in the proximal tubule. Since there is no information regarding the effects of gentamicin on renal peptide carriers, uptake of [3H]pGlu-His was measured in BBMV following either in vivo or in vitro exposure to the antibiotic. One hour after in vivo administration, the maximal rate (Vmax) for pGlu-His transport was significantly reduced in isolated membrane vesicles washed free of the drug, but the apparent Michaelis constant (Km) was unaltered. Coincubation of membranes with gentamicin during measurements of pGlu-His uptake had a similar effect, causing a significant decrease in the Vmax but not the Km of transport. The addition of 5 mM magnesium to the uptake medium prevented the in vitro but not the in vivo effect. The data indicate that high doses of gentamicin inhibit the capacity but not the affinity of dipeptide transport in the kidney, prior to morphological changes which typify acute tubular necrosis. The in vitro effect is rapid and involves a direct action of gentamicin on the brush-border membrane. The in vivo experiments show that toxicity may be prolonged and remains following removal of the drug from the renal brush border.

The reflective educator.

Since the Boulder conference on training in clinical psychology in 1949, at least 13 national conferences have been convened to examine issues in training for practice in psychology, all based on the assumption that extensive training is required to develop professional skills in psychotherapy, psychodiagnosis, and related professional functions. This assumption is challenged by a large body of research that fails to show any relationship between training and efficacy in common forms of practice. Educators of professional psychologists are urged to heed the challenge closely and examine its implications critically. At the same time, educators of researchers in psychology are encouraged to examine common assumptions about the nature of practice in psychology and to consider conceptions of professional work that emphasize reflection in action and disciplined inquiry, rather than psychotherapy and psychodiagnosis, as defining features. Education for practice is neither science nor art, but a profession in itself. When the educational process is approached from this vantage point, novel opportunities for systematic investigation emerge. Decisive studies of the appropriate kind have yet to be done.

Biochemical discrimination between luminal and abluminal enzyme and transport activities of the blood-brain barrier.

Luminal and abluminal membrane vesicles derived from bovine brain endothelial cells, the site of the blood-brain barrier, were fractionated in a discontinuous Ficoll gradient. A mathematical analysis was developed to determine the membrane distribution of membrane marker enzyme activities as well as the ratio of luminal to abluminal membrane in each fraction of the gradient. The results of this analysis indicate that gamma-glutamyl transpeptidase and amino acid transport system A are located on the luminal and abluminal membranes, respectively. Conversely, 5'-nucleotidase and alkaline phosphatase activities are evenly distributed between both membranes. Although Na+/K(+)-ATPase activity is primarily located on the abluminal membrane, approximately 25% of the activity is of luminal origin. Na+/K(+)-ATPase activities associated with each membrane showed different ouabain sensitivities, suggesting that different isoenzymes are located in luminal and abluminal membranes. The analytical procedure used in this study provides a quantitative means to determine the distribution of marker enzymes and transport proteins in partially purified membrane vesicle populations.

Neutral amino acid transport characterization of isolated luminal and abluminal membranes of the blood-brain barrier.

The neutral amino acid carrier composition of luminal and abluminal membranes of the blood-brain barrier has been studied using isolated membrane vesicles. Phenylalanine was carried almost exclusively by a high affinity (Km = 10 +/- 2 microM), Na(+)-independent amino acid transport system, presumably L1 system, that was found to be symmetrically distributed between luminal and abluminal membranes. Inhibition of phenylalanine uptake was used to determine the affinities (Ki values) toward leucine (17 +/- 3 microM), tryptophan (8 +/- 1), 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCH) (11 +/- 2), alanine (628 +/- 117), and glutamine (228 +/- 51). Alanine was found to be transported by two Na(+)-dependent transport systems that were located exclusively on the abluminal membrane. Kinetic and inhibition experiments indicated that one of these activities was due to system A, which is probably the main route for Na(+)-dependent alanine transport (Km = 0.6 +/- 0.2 mM) under physiological conditions. The other Na(+)-dependent activity was attributed to a B(o,+)-like system based on its sensitivity toward BCH. This latter system showed greater affinity for large neutral amino acids. The affinities of these two transport systems for several other amino acids were also studied.

Nephrotic syndrome and acute renal failure associated with hepatitis A virus infection.

Acute renal failure has been documented in association with hepatitis A virus (HAV) infection. This report describes a temporal relationship between HAV infection and immune complex mesangial proliferative glomerulonephritis associated with nephrotic syndrome. Animal experimental data have already shown that this is indeed a histological lesion associated with HAV infection. This case report is the first English documentation associating HAV infection with immune complex mesangial proliferative glomerulonephritis.

Parameter sensitivity of a model of viral epidemics simulated with Monte Carlo techniques. IV. Parametric ranges and optimization.

A model is presented of the spread of influenza into and within a nursing home. To use this model for studies involving surveillance and vaccine efficacy, it is necessary to estimate optimal ranges of a group of parameters. Attempts to do so by manual methods proved unsatisfactory. Initial use of the methods presented in the previous three papers of this series led to points that were also unsatisfactory. However, by noting which parameters were placed at the outer surface of the chosen hypervolume, it was possible to choose new ranges and to select an optimal point in hyperspace that satisfied the epidemiologically preselected characteristics.

Neutral amino acid transport by the blood-brain barrier. Membrane vesicle studies.

Endothelial cell membranes, the site of the blood-brain barrier, were obtained from the capillaries of cow brain. The luminal and abluminal membranes were separated by centrifugation on a discontinuous Ficoll gradient. Electron microscopy revealed that the membrane preparations consisted almost entirely of sealed vesicles. The release of latent enzyme activity showed that both membrane preparations were primarily right side out. Radiolabeled L-phenylalanine uptake by luminal vesicles was proportional to membrane protein concentration, with less than 10% binding. Transport was by a high affinity carrier (Km 11.8 +/- 0.1 microM, asymptotic standard error) that showed little or no stereospecificity, and was independent of Na+ or H+ gradients. Transport was inhibited by L-tryptophan, L-leucine, 2-aminobicyclo[2,2,1]heptane-2-carboxylate and D-phenylalanine, but not by N-(methylamino)-isobutyrate. Abluminal membranes showed an additional component in which a Na+ gradient accelerated the transport of both phenylalanine and N-(methylamino)-isobutyrate. These studies demonstrate the utility of membrane vesicles as a model to characterize the transport properties of the distinct membranes of the polar endothelial cells that form the blood-brain barrier.