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Objective The aim of the study was to compare the relative predictive value of Marshall Classification System and Rotterdam scores on long-term rehabilitation outcomes. This study hypothesized that Rotterdam would outperform Marshall Classification System. Design The study used an observational cohort design with a consecutive sample of 88 participants (25 females, mean age = 42.0 [SD = 21.3]) with moderate to severe traumatic brain injury who were admitted to trauma service with subsequent transfer to the rehabilitation unit between February 2009 and July 2011 and who had clearly readable computed tomography scans. Twenty-three participants did not return for the 9-mo postdischarge follow-up. Day-of-injury computed tomography images were scored using both Marshall Classification System and Rotterdam criteria by two independent raters, blind to outcomes. Functional outcomes were measured by length of stay in rehabilitation and the cognitive and motor subscales of the Functional Independence Measure at rehabilitation discharge and 9-mo postdischarge follow-up. Results Neither Marshall Classification System nor Rotterdam scales as a whole significantly predicted Functional Independence Measure motor or cognitive outcomes at discharge or 9-mo follow-up. Both scales, however, predicted length of stay in rehabilitation. Specific Marshall scores (3 and 6) and Rotterdam scores (5 and 6) significantly predicted subacute outcomes such as Functional Independence Measure cognitive at discharge from rehabilitation and length of stay. Conclusions Marshall Classification System and Rotterdam scales may have limited utility in predicting long-term functional outcome, but specific Marshall and Rotterdam scores, primarily linked to increased severity and intracranial pressure, may predict subacute outcomes.

Self-determination theory (SDT) posits that human well-being depends on the satisfaction of three basic psychological needs: autonomy, competence, and relatedness. Although many scholars have suggested that SDT may be relevant to psychotic disorders, only one empirical study of SDT in individuals with psychosis has been completed to date by Breitborde and colleagues (2012). This study revealed that individuals with first-episode psychosis reported lower satisfaction of the three basic psychological needs as compared to individuals without psychosis. Moreover, greater satisfaction of basic psychological needs was modestly associated with lower general symptoms (e.g., anxiety and depression), greater social functioning, and better quality of life. Thus, the goal of this project was to replicate Breitborde et al.’s (2012) investigation of basic psychological need satisfaction among individuals with first-episode psychosis. Our results supported the conclusion that individuals with first-episode psychosis report lower autonomy, competence, and relatedness than individuals without psychosis. Moreover, our results comport with the finding that greater need satisfaction was associated with less severe symptomatology and better social functioning and quality of life. In total, the findings lend further credence to the hypothesis that SDT may help to inform the development of improved clinical services for individuals with psychotic disorders.

Aim Auditory hallucinations are hypothesized to be based in distorted sensory perceptions, with increasingly distorted perceptions of reality possibly prompting the first psychotic phase of schizophrenia spectrum disorders. Our goal was to examine the association between distorted auditory perceptions and psychotic symptomatology, social functioning and quality of life among individuals with first-episode psychosis. Methods Forty individuals with first-episode psychosis completed assessments of distorted auditory perception, psychotic symptomatology, social functioning and quality of life. Results Both negative (greater symptomatology) and positive clinical correlates (better quality of life) were associated with greater distorted auditory perceptions. Conclusions Our findings suggest that distorted auditory perceptions are associated with both positive and negative clinical correlates among individuals with first-episode psychosis. These results highlight the potential clinical importance of balancing the goal of symptomatic reduction with the need to maintain healthy coping strategies that may be biologically and psychologically entwined with the symptoms of psychosis, themselves.

Studies of traumatic brain injury (TBI) among adult populations demonstrate that such injuries can lead to aggressive behaviors. Related findings suggest that incarcerated individuals have high rates of brain injuries. Such studies suggest that traumatic brain injury may be related to the etiology and recidivism of criminal behavior. Relatively few studies have examined the prevalence of TBI using a delinquent juvenile sample. In order to assess the relationship between TBI and juvenile offender status, the current study used meta-analytic techniques to examine the odds of having a TBI among juvenile offenders. Across 9 studies, we found that approximately 30% of juvenile offenders have sustained a previous brain injury. Across 5 studies that used a control group, a calculated summary odds ratio of 3.37 suggests that juvenile offenders are significantly more likely to have a TBI compared to controls. Results suggest that the rate of TBIs within the juvenile offender population is significant and that there may be a relationship between TBIs and juvenile criminal behavior.

Traumatic brain injury (TBI) is a significant public-health concern. To understand the extent of TBI, it is important to assess the prevalence of TBI in the general population. However, the prevalence of TBI in the general population can be difficult to measure because of differing definitions of TBI, differing TBI severity levels, and underreporting of sport-related TBI. Additionally, prevalence reports vary from study to study. In this present study, we used meta-analytic methods to estimate the prevalence of TBI in the adult general population. Across 15 studies, all originating from developed countries, which included 25,134 adults, 12% had a history of TBI. Men had more than twice the odds of having had a TBI than did women, suggesting that male gender is a risk factor for TBI. The adverse behavioral, cognitive and psychiatric effects associated with TBI coupled with the high prevalence of TBI identified in this study indicate that TBI is a considerable public and personal-health problem.

Expansion management of aluminum/stainless steel power rail due to thermal cycling is critical for long service life of the system and can be addressed by a variety of methods. The high relative expansion rate of aluminum, combined with heating due to electric current flow, climatic conditions and the need to maintain electrical continuity, makes design coordination of the power rail, guideway, and current collector critical to system performance and reliability. Improper expansion management can cause excessive wear of and damage to current collectors, shoes, power rail and power rail accessories, resulting in high maintenance costs and loss of service. Power rail expansion joints must manage the movement of the power rail due to thermal expansion, work in parallel with guideway structural expansions, and maintain an electrical connection with the train. It is best to address the design characteristics of the guideway, collector shoe and power rail expansion joints early in the system configuration. Designers must understand the environmental, physical, and electrical conditions of the entire system to properly design, locate and install expansion joints. This paper examines proper and improper design, location, and installation through real world examples. The authors offer key considerations for proper expansion management and optimal system performance.

Intimate partner violence (IPV) is widespread. Several risk factors are associated with IPV perpetuation, including alcohol use and educational level. The aggression and violence associated with traumatic brain injury (TBI) suggest that brain trauma may also be a risk factor for IPV. To examine the association between TBI and IPV, the authors conducted a meta-analysis of peer-reviewed published studies reporting the prevalence of TBI in IPV perpetrators. The authors compared the frequency of TBI among IPV perpetuators to estimates of TBI in the general population using a single-sample test of proportions. Six studies containing a total of 222 subjects met inclusion criteria. Fifty-three percent (119) of the IPV perpetuators had a history of TBI, a prevalence significantly higher (p < .0001) than estimates of TBI in the general population. The prevalence of TBI among perpetuators of IPV appears significantly higher than the prevalence of TBI in the general population. To the extent that this association is causal, TBI may be a risk factor for interpersonal violence, although comparatively few source studies, lack of standardized information about TBI severity, and the inability to investigate potential confounding variables necessarily limit this conclusion.

Ganglioside GM2 and its asialo-derivative, GA2 were radiolabeled in their N-acetyl-D-galactosaminyl moieties by oxidation with galactose oxidase and reduction with tritiated sodium borohydride. Specific activities of 6 X 10(4) dpm/nmol (GM2) and 1.8 X 10(6) dpm/nmol (GA2) were achieved. About 98% of the label was in N-acetyl-D-galactosamine. Using these substrates, an assay was developed for GM2-N-acetyl-beta-D-galactosaminidase (E.C.3.2.1.30) and GA2-N-acetyl-beta-D-galactosaminidase (E.C.3.2.1.30) activities in human cultured skin fibroblasts. The products of the GM2 cleaving reaction were identified as N-acetylgalactosamine and ganglioside GM3. Both GM2 and GA2 cleaving activities were stimulated about 5-fold by purified sodium taurocholate, and this stimulation was inhibited by neutral detergents, lipids and albumin at low concentrations. Addition of various salts, reducing agents and a protein activator factor from human liver of Li et al. (1973) did not stimulate GM2-N-acetyl-beta-D-galactosaminidase activity beyond that found with sodium taurocholate. Under optimal conditions, control fibroblast supernates cleaved ganglioside GM2 at a rate of 3.7 nmol/mg protein/h compared to 1100 for GA2-N-acetyl-beta-D-galactosaminidase and 4700 for 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminidase. Supernates from two patients with Tay-Sachs disease had markedly reduced activity levels for GM2-N-acetyl-beta-D-galactosaminidase but not for the other two substrates. Supernates from two patients with Sandhoff's disease had reduced activities for all three substrates. A supernate from one patient with juvenile GM2 gangliosidosis cleaved GM2 at a somewhat faster rate than those from Tay-Sachs or Sandhoff's patients. Two healthy adult women with markedly reduced hexosaminidase A activities using 4MU-N-acetyl-beta-D-glucosaminide as substrate had approximately half-normal activities using GM2 as substrate. A patient with the Tay-Sachs phenotype but with a partial deficiency of hexosaminidase A using the 4-MU substrate had a profound deficiency using GM2 as substrate. In such unusual hexosaminidase mutants, assays using GM2 as substrate are better indicators of phenotype than those using synthetic substrates.

Reasons are advanced for the apparent lack of use by designers in industry of the design methods provided by Design Science. Suggestions for the alleviation of this situation are also advanced.

R-matrix calculations for neutral (N I) and singly ionized nitrogen (N II) have been carried out in the energy region below 50 eV for N I and 180 eV for N II, respectively. The collision strengths were calculated for optical allowed and forbidden transitions as well as for exchange transitions involving energy levels with principal quantum numbers n⩽3. In both atomic systems, spectroscopic measurements in the visible and vacuum-ultraviolet spectral range have been performed in order to investigate several rate coefficients in the theoretically uncertain near-threshold regions. For this purpose seven N I- and sixteen N II-rate coefficients were determined by means of a 7 mm diameter stationary cascade arc discharge operated at a current of 8 A and different pressures in the range from 1 to 30 hPa. The spectroscopic system for the vacuum-ultraviolet wavelength range was intensity calibrated by means of the continuum radiation of a normal pressure pure helium arc discharge and the calibrated line emission of...

Auditory hallucinations are hypothesized to be based in distorted sensory perceptions, with increasingly distorted perceptions of reality possibly prompting the first psychotic phase of schizophrenia spectrum disorders. Our goal was to examine the association between distorted auditory perceptions and psychotic symptomatology, social functioning and quality of life among individuals with first-episode psychosis.Forty individuals with first-episode psychosis completed assessments of distorted auditory perception, psychotic symptomatology, social functioning and quality of life.Both negative (greater symptomatology) and positive clinical correlates (better quality of life) were associated with greater distorted auditory perceptions.Our findings suggest that distorted auditory perceptions are associated with both positive and negative clinical correlates among individuals with first-episode psychosis. These results highlight the potential clinical importance of balancing the goal of symptomatic reduction with the need to maintain healthy coping strategies that may be biologically and psychologically entwined with the symptoms of psychosis, themselves.

The aim of the present investigation was to determine whether there is a net uptake of insulin-like growth factor I (IGF-I) or IGF-binding proteins (IGFBPs) by the leg after burn injury and to elucidate the regulatory role of insulin exerted on this system under in vivo conditions in burn patients. Studies were performed on nine patients after burn injury (approximately 60% body surface area). Each patient was studied twice during a continuous infusion of a carbohydrate-rich enteral diet. Blood was collected simultaneously from the femoral artery and vein for the measurement of various elements of the IGF system after 7 days of enteral diet alone (basal period) and after 7 days of the enteral diet plus the infusion of insulin (insulin period). Data from these patients were compared to values in age-matched fed healthy volunteers. During the basal period, burn patients demonstrated a significant reduction in the venous concentration of IGF-I and an increase in both IGFBP-1 and -2 compared to control values. Insulin produced a significant 15% increase in the IGF-I concentration in burn patients, but decreased the circulating levels of IGFBP-1 by 50%. The IGF-I and IGFBP-1 concentrations at the end of the insulin period were still significantly different from those in control subjects. Burn patients also exhibited a marked reduction in intact IGFBP-3 and the acid-labile subunit under basal conditions, and these alterations were not reversed by insulin. Under basal conditions, all burn patients had a positive arterio-venous (A-V) difference for IGF-I across the leg. The A-V difference was increased 50% in response to insulin. The net uptake of IGF-I by the leg was 2.4 micrograms/min under basal conditions, and as leg blood flow also tended to increase in response to insulin, IGF-I uptake was elevated more than 3-fold during the insulin period. No A-V difference across the leg was detected for IGFBP-1, -2, or -3 in burn patients. In conclusion, burn injury in humans produces dramatic and sustained alterations in various components of the IGF system that persist despite adequate nutritional support. Our data indicate the presence of a net uptake of IGF-I by the leg in burn patients that may serve to counteract the catabolic state.

Empirical evidence indicates that the dissatisfaction with one’s body is widely present in the general population even at very early ages, and that it is predictive of future eating disorders. The family seem particularly influent for the development of body dissatisfaction while sports practice is associated to a higher prevalence of disordered eating. However the role of sports practice in the development of body dissatisfaction is still under debate and only few studies have evaluated together the influences of family and sport practice on body dissatisfaction. The present study aimed at evaluating both the singular and conjoint role of the type of sport and maternal influences in young female children. The sport influence was assessed comparing aesthetic and non-aesthetic disciplines; the mother’s influence was evaluated considering her personal characteristics and her desire to have a thinner child. Results evidence that children involved in aesthetic sports, although thinner than those involved in non-aesthetic sports, report higher desire to be much thinner and have mothers who pressure them toward a greater thinness. Furthermore, children’s body dissatisfaction in the sport groups is predicted by maternal characteristic like her habit to restrict her own eating and her perfectionism.

Improved design and performance of continuous thickeners should be achieved through a better understanding of the sludge transport processes involved and the variability of sludge thickenability. A software package called PHOENICS was used to model the three-dimensional flow of sludge in the transport zone of a 20m diameter thickener. A mass transport efficiency was evaluated to test the efficacy of the ploughing system, and tracer simulations were performed to study the degree of back-mixing induced. Interpretation of the results suggests that:○Optimum orientation of the ploughs to the radial arm is 60° to 70°.○Transport of sludge to a central outlet occurs principally in the wake of the advancing ploughs, and that ploughs are less efficient than conventional theories dictate.○Sludge in the ploughing zone is mixed, thus potentially impairing thickener performance. The thickenability of mixed raw sludge arising at a large activated sludge works was monitored. Pronounced seasonal variations were observed, with a marked deterioration in thickenability in late summer and autumn. These were confirmed in trials of a 20m diameter continuous thickener. Consequently the proposed thickening strategy for this works has been revised.

A pharmacokinetic dosing study with camphor was used to determine whether selection lines of high-juniper-consuming goats (HJC, n = 12) and low-juniper-consuming goats (LJC, n = 12) differed in their respective disposition kinetics. Postdosing plasma camphor concentrations were used to examine whether a timed single blood sample collected after intraruminal administration of camphor would be a useful screening test to aid in the identification of HJC. Yearling female Boer x Spanish goats (n = 24) received a single intraruminal dose of monoterpene cocktail (0.270 g/kg of BW) containing 4 different monoterpenes that represented their composition previously reported for Ashe juniper (Juniperus ashei). Camphor, the predominant monoterpene in Ashe juniper, was 49.6% of the mix and was the monoterpene analyzed for this study. Blood samples were taken at 15 time points from 0 to 8 h after dosing. Concentrations of camphor were measured in plasma using solid phase extraction and gas chromatography/flame-ionization detection analysis. Maximal plasma concentration of camphor was greater for LJC than HJC (P = 0.01), and area under the curve extrapolated to infinity was greater for LJC than HJC (P0.01). Total systemic exposure (area under the curve) to camphor was 5 times less in HJC goats. We conclude that 1) HJC goats possess internal mechanisms to reduce the bioavailability of camphor, and 2) a blood sample taken at 45 min or at 60 min after intraruminal administration of camphor may be useful for identifying HJC individual animals from within large populations of goats.

This paper describes a fast direct algorithm for obtaining least-squares phase estimates from arrays of noisy phase differences. The algorithm uses the fast Fourier transform to diagonalize and decouple the system of equations which results from the application of the least-squares criterion. It is accurate and stable, and is perhaps an order of magnitude faster than the best iterative method. The effectiveness of the algorithm has been demonstrated by using it in connection with the Knox–Thompson speckle-imaging procedure to restore an optical object perturbed by simulated atmospheric turbulence. Representative results are discussed in the paper.

Commonly useful properties of directed graphs and their adjacency matrices are briefly reviewed. Some misconceptions presented in earlier papers, relating to indicators in the adjacency matrix of the occurrence of multiple laps of cycles and of compound cycles composed of several shorter cycles, are corrected. Shortcomings of an earlier method for finding cycles are discussed and a simple, improved method for finding all cycles, or all paths between two nodes of interest, is presented. Shortcomings of an earlier method of suppressing unwanted cycle effects are discussed and a simple, improved method for this is presented. Results obtained from this method are compared with those for the same case where cycle suppression is not used.

The insulin-like growth factor-binding protein IGF-BP1 is a major secretory protein of human endometrial stromal cells decidualized in culture. Anion exchange chromatography and nondenaturing gel electrophoresis showed IGF-BP1 to exist in five electrophoretically and chromatographically distinct isoforms. IGF-BP1 variants migrated as a quintet on nondenaturing polyacrylamide gels and as a single band (28 kDa) on sodium dodecyl sulfate-polyacrylamide gels. Alkaline phosphatase treatment reduced the IGF-BP1 variants to a single band. Cells incubated with [32P]orthophosphate for 12 h secreted four 32P-labeled IGF-BP1 phosphovariants, and their migration coincided with those bands that were eliminated by alkaline phosphatase treatment. In cells treated with medroxyprogesterone acetate and relaxin, the concentration of phosphorylated IGF-BP1 was increased dramatically as compared with controls. All the phosphovariants were confirmed to be IGF-BP1 by their ability to be supershifted on nondenaturing polyacrylamide gels after binding a monoclonal antibody to IGF-BP1. Thin layer electrophoresis of IGF-BP1 acid hydrolysates showed IGF-BP1 to be phosphorylated exclusively on serine. Non-phosphorylated IGF-BP1 was phosphorylated by the catalytic subunit of the cAMP-dependent protein kinase and casein kinase II in vitro. This suggests that IGF-BP1 may be a substrate of multiple protein kinases in vivo.

Skeletal muscle demonstrates great plasticity in response to environmental and hormonal factors including pathogen-associated molecules, inflammatory cytokines, and growth factors. These signals impinge on muscle by forcing individual muscle fibers to either grow or atrophy. We recently demonstrated that skeletal muscle cells express multiple Toll-like receptors (TLR) that recognize bacterial cell wall components, such as lipopolysaccharide (LPS). Exposure of myocytes to LPS and other TLR ligands initiates an inflammatory response culminating in the autocrine production of cytokines and NO by NO synthase (NOS)2. The TLR signal through protein kinases that phosphorylate and promote the degradation of an inhibitory protein that normally retains the transcription factor, nuclear factor kappaB (NFkappaB), in the cytoplasm. Phosphorylation and degradation of the inhibitor of NFkappaB allows for translocation of NFkappaB to the nucleus and activation of inflammatory genes. Overexpression of a constitutively active inhibitor of NFkappaB kinase in skeletal muscle causes severe wasting, and we found that inhibitors of either the phosphorylation of IkappaB or its proteolytic degradation prevent TLR ligand-induced expression of cytokines and NOS2. The combination of LPS and interferon gamma dramatically enhances the magnitude and duration of LPS-stimulated NOS2 expression and reduces protein translation. Lipopolysaccharide and interferon gamma also downregulates signaling from the mammalian target of rapamycin, a kinase that directs changes in cell size. Inhibitors of NOS block the fall in muscle cell protein synthesis and restore translational signaling, indicating that activation of the NOS2-NO pathway is responsible for the observed decrease in muscle protein synthesis. Our work provides a molecular explanation for reduced muscle growth during infection. Muscle is largely self-sufficient because it expresses receptors, signaling pathways, and effectors to regulate its own size. Prolonged activation of NFkappaB and NOS2 have emerged as detrimental facets of the immune response in muscle. The interplay between inflammatory components and growth factor signaling clearly places muscle at the interface between growth and immunity.

The treatment and disposal of sewage sludge in environmentally conscious societies is becoming increasingly problematical due, in large part, to public attitudes. Strategies have to be developed which either successfully defend existing routes or which manage changes that have public support. A case study of managing change at a large wastewater treatment plant, serving Gothenburg, Sweden, is presented. Three radically different alternatives to the current practice, of lime addition to dewatered raw sludge and disposal to land reclamation, were appraised to a common set of criteria and compared with the existing route. The options considered were incineration, drying of dewatered anaerobically digested sludge, and disposal of dewatered anaerobically digested sludge to underground cavities. An account is given of the public discussion meetings that were held at strategically important times, the views expressed at these being taken into account by GRYAAB's management board in their decision to opt for the disposal of sludge to underground cavities.

Whole-leg calipers, extending from the heel to the groin region, have traditionally employed knee joints that remain locked throughout the gait cycle, thereby imposing disadvantages in the dynamics, energy utilization and cosmesis of the resulting gait. A design concept is presented for a knee joint that will allow the knee joint to automatically unlock and relock at appropriate points in the gait cycle, to allow a swing-through gait style to be used.

In this paper we describe a database interface that is loosely based upon some of theconcepts proposed by Richard Montague in his approach to the interpretation of natural language. The system is implemented as an executable attribute grammar specified in a higher order, lazy, pure functional programming language. The attribute grammar formalism provides a simple means of implementing Montague's notion of “semantic rule to syntactic rule correspondence” and the higher order functional language in which the attribute grammar is constructed provides an appropriate vehicle for implementing Montague's higher order semantics. The purpose of the paper is two-fold: (i) to demonstrate that many of Montague's ideas can be used to advantage in creating natural language interfaces to databases, and (ii) to introduce a method for implementing attribute grammars in functional languages that is suitable for investigating both grammars and semantic theories of language.

Metal silicide thin films on single‐crystal silicon substrates are the subject of much research, due to their applications as electrical contacts and interconnects, diffusion barriers, low resistance gates, and field‐assisted positron moderators, among others. Defects within the silicide layer and/or at the silicide/silicon interface are detrimental to device performance, since they can act as traps for charge carriers, as well as positrons. Pinholes penetrating the film are another detriment particularly for cobalt silicide films, since they allow electrons to permeate the film, rather than travel ballistically, in addition to greatly increasing surface area for recombination events. A series of epitaxial cobalt and nickel silicide thin films, deposited via electron‐beam evaporation and annealed at various temperatures, have been grown on single‐crystal silicon (111) substrates, in an effort to establish a relationship between deposition and processing parameters and film quality. The films have been ana...

Videofluoroscopy has become the gold standard investigation for assessment of aspiration in patients with clinically diagnosed dysphagia due to neurological causes. Modified nasendoscopy has been described for detection of aspiration with varying findings. Milk nasendoscopy is a simple clinic-based technique to evaluate swallow dysfunction, requiring no radiological input. This paper aims to review the correlation of milk nasendoscopy and videofluoroscopy in the detection of aspiration among patients with clinically diagnosed neurological dysphagia. Retrospective notes of 100 patients attending a combined Swallow Clinic for clinically diagnosed aspiration were reviewed. All patients were subjected to both milk nasendoscopy and videofluoroscopy. Correlation of investigation results was reviewed by Kappa test, and difference was statistically examined with Chi square test. Assessment of aspiration in pre-swallow, swallow and post-swallow phases was reviewed using milk nasendoscopy and videofluoroscopy. The significance of difference was measured using Chi square test. Milk nasendoscopy detected post-swallow phase aspiration significantly more than videofluoroscopy with no significant difference in pre-swallow phase, whereas videofluoroscopy was the investigation of choice in detecting aspiration during the swallow phase. In the investigation of clinically diagnosed neurological dysphagia, substantial correlation was seen in detection between videofluoroscopy and milk nasendoscopy. We suggest that milk nasendoscopy should be used as a preliminary clinic-based test thereby reducing the need for investigations requiring radiation doses.

This paper describes a fast direct algorithm for obtaining least-squares phase estimates from arrays of noisy phase differences. The algorithm uses the fast Fourier transform (FFT) to diagonalize and decouple the system of equations which results from the application of the least-squares criterion. It is accurate and stable, and is perhaps an order of magnitude faster than the best iterative method. The effectiveness of the algorithm has been demonstrated by using it in connection with the Knox-Thompson speckle-imaging procedure to restore an optical object perturbed by simulated atmospheric turbulence.

Saturn's largest moon, Titan, remains an enigma, explored only by remote sensing from Earth, and by the Voyager and Cassini spacecraft. The most puzzling aspects include the origin of the molecular nitrogen and methane in its atmosphere, and the mechanism(s) by which methane is maintained in the face of rapid destruction by photolysis. The Huygens probe, launched from the Cassini spacecraft, has made the first direct observations of the satellite's surface and lower atmosphere. Here we report direct atmospheric measurements from the Gas Chromatograph Mass Spectrometer (GCMS), including altitude profiles of the constituents, isotopic ratios and trace species (including organic compounds). The primary constituents were confirmed to be nitrogen and methane. Noble gases other than argon were not detected. The argon includes primordial 36Ar, and the radiogenic isotope 40Ar, providing an important constraint on the outgassing history of Titan. Trace organic species, including cyanogen and ethane, were found in surface measurements.

Infections direct amino acids away from growth and skeletal muscle accretion toward the hepatic synthesis of acute-phase proteins. The loss of skeletal muscle protein stores results in both a decrease in muscle function and an increase in mortality. In general, muscle protein synthesis is decreased in rodent models of sepsis, as well as after the injection of components of the bacterial cell wall, such as lipopolysaccharide. Although the overexpression of proinflammatory cytokines is known to hasten the loss of skeletal muscle protein, it is not known whether this represents a direct effect of cytokines or results from secondary changes in the IGF system. Plasma concentrations of IGF-I are dramatically lowered by infection in rats, mice, pigs, and steers. The drop in IGF-I often occurs despite an increase in the plasma concentration of somatotropin. Animals are therefore considered to be GH resistant. The IGF bioactivity is determined not only by the plasma concentration of the ligand, but also by IGFBP; IGFBP-3 is the most abundant of these binding proteins and undergoes proteolysis during some catabolic states. In contrast to IGFBP-3, the plasma concentration of inhibitory IGFBP, such as IGFBP-1, is increased during infection. Insulin-like growth factor-binding protein-1 accumulates in skeletal muscle, where it can potentially inhibit IGF-dependent protein synthesis. Insulin-like growth factor-I and IGFBP-1 are regulated at the level of gene transcription by proinflammatory cytokines. Recent studies demonstrate that bacterial components that activate immune cells also activate the innate immune response in skeletal muscle. Lipopolysaccharide increases proinflammatory cytokine messenger RNA expression in muscle from control mice, but not from mice with a mutation in the lipopolysaccharide receptor. Lipopolysaccharide also increases cytokine expression in human and mouse myoblasts. Local expression of cytokines in skeletal muscle may negatively regulate the autocrine synthesis of IGF-I. Current work is focused on deciphering the mechanism by which muscle becomes GH resistant and the development of therapies to maintain muscle protein stores during infection.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are potent regulators of muscle mass. Transgenic mice that over-express these proteins exhibit dramatically enlarged skeletal muscles. In contrast, malnutrition, critical illness, sepsis, and aging are all associated with a dramatic reduction in muscle mass and function. The circulating concentration of IGF-I and the expression of IGF-I in skeletal muscle are also reduced during catabolic states. Consequently, GH has been used clinically to increase lean body mass in patients with muscle wasting. Likewise, delivery of IGF-I specifically into muscle has been proposed as a genetic therapy for muscle disorders. A better understanding of the regulation of IGF-I expression in skeletal muscle and muscle cells is therefore of importance. Yet, our knowledge in this area has been limited by a lack of GH responsive muscle cells. In addition the IGF-I gene spans over 90 kb of genomic DNA and it exhibits a very complex regulatory pattern. This review will summarize our knowledge of the control of muscle mass by GH, IGF-I, anabolic steroids, exercise and other growth enhancing hormones. We will also highlight recent advances in the regulation of IGF-I and signal transducers and activators of transcription (Stats) by GH. A special emphasis will be placed on the interaction of IGF-I and proinflammatory cytokines in skeletal muscle and muscle cells.

The Gas Chromatograph Mass Spectrometer (GCMS) on the Huygens Probe will meas- ure the chemical composition of Titan's atmosphere from 170 km altitude (∼ 1h Pa) to the surface (∼1500 hPa) and determine the isotope ratios of the major gaseous constituents. The GCMS will also analyze gas samples from the Aerosol Collector Pyrolyser (ACP) and may be able to investigate the composition (including isotope ratios) of several candidate surface materials. The GCMS is a quadrupole mass filter with a secondary electron multiplier detection system and a gas sampling system providing continuous direct atmospheric composition measurements and batch sampling through three gas chromatographic (GC) columns. The mass spectrometer employs five ion sources sequentially feeding the mass analyzer. Three ion sources serve as detectors for the GC columns and two are dedicated to direct atmosphere sampling and ACP gas sampling re- spectively. The instrument is also equipped with a chemical scrubber cell for noble gas analysis and a sample enrichment cell for selective measurement of high boiling point carbon containing constituents. The mass range is 2 to 141 Dalton and the nominal detection threshold is at a mixing ratio of 10 −8 . The data rate available from the Probe system is 885 bit/s. The weight of the instrument is 17.3 kg and the energy required for warm up and 150 minutes of operation is 110 Watt-hours.

There are many forms of vibrational spectroscopies applied to surfaces but the most accessible techniques are Fourier transform infrared spectroscopy and Raman spectroscopy. They will be discussed in this chapter. Other vibrational spectroscopies (e.g. PAS, EELS) are listed in the Appendix and Bibliography.

The results of this study support the notion that pathological gamblers drawn from the community would score higher on all three scores from the YBOCS than light gamblers. Consistent with hypotheses, pathological gamblers (lottery and scratch ticket) reported more obsessions, compulsions, and avoidance behavior than the light gamblers, and also reported having more urges to engage in injurious behaviors to themselves and others. These findings provide evidence that pathological gambling falls in a spectrum or family of disorders which have obsessive-compulsive disorder at its core. These findings support McElroy, Hudson, Philips, et al.'s (1993) suggestions of similarities between OCD and Impulse Control Disorders, and extend Blaszczynski (1999) findings of overlap between pathological gamblers and OCD in a treatment population. Heavy gamblers also reported significantly more hoarding symptoms and compulsive buying than light gamblers. More research in this area may show further evidence of a spectrum of disorders with obsessive compulsive disorder at its core, and show further links between impulse control disorders (such as pathological gambling) and OCD.

Acute and chronic alcohol intoxication decreases skeletal muscle protein synthesis under in vivo conditions. We investigated whether ethanol (EtOH) and its major metabolites, acetaldehyde and acetate, can directly modulate protein balance under in vitro conditions.Human myocytes were incubated with different doses of EtOH for varying periods of time (i.e., 4-72 hr). Alternatively, cells were incubated with acetaldehyde, acetate, insulin, insulin-like growth factor-I (IGF-I), or with a combination of EtOH plus insulin or IGF-I. Rates of protein synthesis or degradation were determined by 35S-methionine/cysteine incorporation into or release from cellular protein.A significant, 15% to 20%, decrease in basal protein synthesis was observed after 24 hr, but not at earlier time points, in response to 80 mM EtOH. Incubation of myocytes for 72 hr decreased synthesis in cells incubated with EtOH ranging between 60 and 120 mM. The ability of IGF-I or insulin to stimulate protein synthesis was impaired by 30% and 60%, respectively, in cells incubated with 80 mM EtOH for 72 hr. Exposure of cells to 200 microM acetaldehyde or 5 mM Na-acetate also decreased basal protein synthesis. In contrast, neither EtOH, acetaldehyde, nor acetate altered the basal rate of protein degradation. However, EtOH completely impaired the ability of insulin and IGF-I to inhibit proteolysis. Finally, EtOH did not impair IGF-I receptor autophosphorylation, but inhibited the ability of insulin to phosphorylate its own receptor. EtOH also did not alter the number of insulin or IGF-I receptors or the formation of insulin/IGF-I hybrid receptors.We have demonstrated that EtOH can directly inhibit muscle protein synthesis under in vitro conditions. Neither EtOH nor its metabolites altered basal protein degradation, although EtOH did compromise the ability of both insulin and IGF-I to slow proteolysis. This impairment seems to be mediated by different defects in signal transduction.

This study was designed to determine the effects of an aluminum hydroxide antacid and a calcium carbonate antacid on the bioavailability of ciprofloxacin (Cipro). Cipro (750 mg) was administered orally to 12 healthy volunteers in a three-way randomized crossover design. The three treatments included Cipro alone, four 850-mg calcium carbonate tablets taken 5 min before Cipro, and three 600-mg aluminum hydroxide tablets taken 5 min before Cipro. The relative bioavailability of Cipro when given with calcium carbonate was approximately 60% of the control value. When Cipro was given with aluminum hydroxide, the relative bioavailability was approximately 15%. Urinary recovery of Cipro in the aluminum hydroxide treatment group was approximately one-fourth of that in the calcium carbonate group. Although calcium carbonate decreased absorption to a lesser extent than aluminum hydroxide, these data suggest that antacids containing either aluminum or calcium should not be given concomitantly with Cipro.

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is a 28-kDa plasma protein that binds to IGF-I and IGF-II with high affinity. IGFBP-1 is elevated in the blood as a result of sepsis, AIDS, excessive alcohol consumption, and diabetes and may, in part, be responsible for the wasting observed during these pathophysiological conditions. The liver is the principal site of IGFBP-1 synthesis, and we have previously shown that proinflammatory cytokines can directly stimulate IGFBP-1 secretion in a human hepatoma cell line (HepG2). The purpose of the present study was to investigate the role of the MAP kinase pathway in regulating IGFBP-1 synthesis by IL-1beta. We show that IL-1beta stimulates the phosphorylation of ERK-1 and -2 in a time- and dose-dependent manner. In addition, the MAP kinase-kinase MEK-1 and the ribosomal S6-kinase RSK-1 are also phosphorylated in response to IL-1beta. The transcription factor CREB, a potential substrate of both protein kinase A (PKA) and RSK-1, is phosphorylated in response to IL-1beta and cAMP in HepG2 cells. The ability of IL-1beta to stimulate the expression of IGFBP-1 and the phosphorylation of the above kinases was specifically inhibited by PD98059, a MEK-1 inhibitor. cAMP also stimulated IGFBP-1 synthesis, but PD98059 failed to block the cAMP effect. Conversely, a PKA inhibitor (H-89) inhibited the ability of cAMP, but not IL-1beta to stimulate IGFBP-1 synthesis. The effect of IL-1beta and cAMP on IGFBP-1 messenger RNA (mRNA) accumulation was additive. IL-1beta, cAMP, PD98059, and H-89 had similar effects on the accumulation of IGFBP-1 protein and mRNA. IL-1beta and cAMP did not change the half-life of IGFBP-1 mRNA, but PD98059 and SB202190, a p38 MAP kinase inhibitor, destabilized IGFBP-1 mRNA and blocked the phosphorylation of RSK-1 in response to IL-1beta. Our data demonstrate that the MAP kinase signal transduction pathway plays an important role in the regulation of IGFBP-1 synthesis by IL-1beta.

Acute alcohol intoxication in rats decreases protein synthesis in skeletal muscle and, to a lesser extent, in liver. The purpose of the present study was to examine potential mechanisms for the inhibitory effect of acute ethanol exposure.Rats were injected intraperitoneally with either ethanol (75 mmol/kg) or saline, and tissues were examined 2.5 hr later. Rates of protein synthesis in vivo were determined by [3H]phenylalanine incorporation into protein, and various eukaryotic initiation factors (eIFs) were quantitated by Western blot analysis to identify possible mechanisms for regulating translation.Protein synthesis in gastrocnemius and liver was decreased (39% and 21%, respectively) after alcohol administration, compared with saline-injected control animals. Alcohol administration did not alter tissue RNA content but diminished translational efficiency in muscle (43%) and liver (24%). Hepatic eIF2B activity was decreased 24% in alcohol-treated rats, and this was associated with a 95% increase in eIF2alpha phosphorylation. However, alcohol did not alter the amount of 4E-binding protein 1 (4E-BP1) bound to eIF4E, cIF4E bound to eIF4G, or the phosphorylation state of either 4E-BP1 or eIF4E. In contrast to liver, neither eIF2B activity nor the phosphorylation of eIF2alpha was affected in muscle of alcohol-treated rats. However, acute alcohol intoxication increased binding of 4E-BP1 to eIF4E (113%), decreased the amount of cIF4E bound to cIF4G (81%), and decreased the amount of 4E-BP1 in the phosphorylated gamma-form (77%). The plasma concentrations of insulin and insulin-like growth factor-I were unchanged by alcohol, but muscle insulin-like growth factor-I messenger ribonucleic acid abundance was decreased 35%.These data suggest that acute alcohol intoxication decreases translation initiation and protein synthesis in liver and muscle via different mechanisms. Changes in eIF2B appear to predominate in liver, whereas alterations in eIF4E availability appear more critical in skeletal muscle for controlling translation initiation.

The erosion of lean body mass observed during catabolic illness is still a major cause of morbidity and mortality. The known anabolic actions of growth hormone and insulin-like growth factor-I have stimulated interest in the use of these agents to mitigate the loss of muscle protein after injury. This review summarizes advances in our understanding of how nutrition, hormones and proinflammatory cytokines regulate the somatotropic axis in health and disease, and recent studies involving the use of growth hormone or insulin-like growth factor-I in the treatment of critically ill patients.

Insulin-like growth factor-binding protein-1 (BP-1) is a multifunctional protein that binds IGF-I in solution and integrins on the cell surface. BP-1 is overexpressed during catabolic illnesses, and the protein accumulates in skeletal muscle. To define a potential physiological role for BP-1 in regulating muscle protein balance, we have examined the effect of IGF-I and BP-1 on protein synthesis and degradation in human skeletal muscle cells. IGF-I-stimulated protein synthesis by 20%, and this was completely inhibited by either phosphorylated or nonphosphorylated BP-1. Half-maximal inhibition of protein synthesis occurred at a molar ratio of BP-1 to IGF-I of 1.5:1. BP-1 failed to form a complex with a truncated form of IGF-I (desIGF-I), and consequently, BP-1 failed to inhibit the ability of desIGF-I to stimulate protein synthesis. IGF-I and BP-1 dose-dependently inhibited protein degradation individually, and both BP-1 phosphovariants failed to block the ability of IGF-I to do the same. Blocking integrin receptor occupancy with the integrin antagonist echistatin blunted the ability of BP-1 to inhibit protein degradation, but had no significant effect on IGF-I-mediated changes in protein synthesis or degradation. The extracellular matrix protein vitronectin also inhibited protein degradation, but vitronectin receptor antibodies failed to block BP-1 action. In contrast, antibodies to the beta1 integrin subunit blocked BP-1-mediated inhibition of protein degradation. Rapamycin inhibited IGF-I-dependent protein synthesis, but not the ability of IGF-I to inhibit proteolysis. In contrast, rapamycin completely blocked the ability of BP-1 to inhibit proteolysis. Our results demonstrate that BP-1 inhibits IGF-I-mediated protein synthesis by binding to IGF-I. BP-1, acting independently of IGF-I, inhibits protein degradation. The IGF-independent response occurs via beta1 integrin binding and stimulation of a rapamycin-sensitive signal transduction pathway.

Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined. Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 +/- 15%, P = 0.002), patients with asymptomatic HIV (24 +/- 10%, not significant), patients with AIDS (47 +/- 7%, P0.001), and patients with AIDS and10% weight loss (21 +/- 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 +/- 7%, P0.05), HIV+ subjects (39 +/- 16%, P0.05), and patients with AIDS (25 +/- 7%, P0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (-0.6 +/- 12%) in response to hrGH. The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH.