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In this study, we examined the relationship between physiological encoding of surprise and the learning of anticipatory eye movements. Active inference portrays perception and action as interconnected inference processes, driven by the imperative to minimise the surprise of sensory observations. To examine this characterisation of oculomotor learning during a hand–eye coordination task, we tested whether anticipatory eye movements were updated in accordance with Bayesian principles and whether trial-by-trial learning rates tracked pupil dilation as a marker of ‘surprise’. Forty-four participants completed an interception task in immersive virtual reality that required them to hit bouncing balls that had either expected or unexpected bounce profiles. We recorded anticipatory eye movements known to index participants’ beliefs about likely ball bounce trajectories. By fitting a hierarchical Bayesian inference model to the trial-wise trajectories of these predictive eye movements, we were able to estimate each individual’s expectations about bounce trajectories, rates of belief updating, and precision-weighted prediction errors. We found that the task-evoked pupil response tracked prediction errors and learning rates but not beliefs about ball bounciness or environmental volatility. These findings are partially consistent with active inference accounts and shed light on how encoding of surprise may shape the control of action.

The epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium tuberculosis (TB), is notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with a host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB meningitis (TBM) and its mimics. 368 HIV-infected Ugandan adults with subacute meningitis were prospectively enrolled. Total RNA and DNA CSF mNGS libraries were sequenced to identify meningitis pathogens. In parallel, a CSF host transcriptomic MLC to distinguish between TBM and other infections was trained and then evaluated in a blinded fashion on an independent dataset. mNGS identifies an array of infectious TBM mimics (and co-infections), including emerging, treatable, and vaccine-preventable pathogens including Wesselsbron virus, Toxoplasma gondii, Streptococcus pneumoniae, Nocardia brasiliensis, measles virus and cytomegalovirus. By leveraging the specificity of mNGS and the sensitivity of an MLC created from CSF host transcriptomes, the combined assay has high sensitivity (88.9%) and specificity (86.7%) for the detection of TBM and its many mimics. Furthermore, we achieve comparable combined assay performance at sequencing depths more amenable to performing diagnostic mNGS in low resource settings.

The current study presents an experimental analysis of a custom-designed heat exchanger (CDHX), for recovering the waste heat energy of the exhaust gas from a stationary diesel engine. It has triangular external finned tubular construction with its shell flue side fitted with segmental baffles sloped at 20°, to effectively extract heat to raise the tube side circulating thermal oil temperature for sensible heat rise. This, in closed loop, transfers the heat to non-moving, sealed and filled thermal storage system with phase change material (PCM) as the latent heat energy. From the third closed loop circulating water from the thermal storage, it indirectly supplies the heat for steady and peak state process consumptions. Balmerol prototherm medium heat transfer oil and water circulations are used as the respective heat extraction liquid media during the charging and discharging process, with PCM at varied levels of molten conditions. The temperature rise behavior of the heat transfer fluid in the CDHX under different load conditions of the engine is studied. The thermal performance analysis of the CDHX has been evaluated using effectiveness and heat extraction rates. The behavior of PCM temperature in the latent heat thermal energy storage (LHTES) tank during charging and discharging process is studied. The evaluation of the performance of the LHTES system has been analyzed by estimating the charging rate with increased melted liquid and latent heat energy stored during the charging process and discharging rate of PCM during solidification process. It is found that nearly 53–60% of stored material latent heat energy is recovered from the PCM in the LHTES tank. It is used by closed loop hot water circulation during discharging process for steady-state drying of food products to reduce the gap between demand and supply of energy. The maximum heat extraction rate of the CDHX integrated with LHTES tank is 3.9 kW, and the charging rate in the LHTES tank is 1.550 kW at full-load condition of the engine. At the flow rate of water of 6 lpm, the maximum heat discharge rate of PCM in the LHTES tank is 0.710 kW and it decreases to 0.58 and 0.47 kW for reduced 4 and 2 lpm flows, respectively. The water temperature that rises nearly 72 °C during discharging process of LHTES tank for 70-min duration achieved at the flow rate of 6 lpm.

This study deals with the thermodynamic analysis of a compression ignition (CI) engine coupled with a longitudinal triangular finned tube construction in a shell and tube heat exchanger which has segmental baffle cut of 50% at 20° slope and a latent heat thermal storage (LHTS) unit, using nano-enhanced organic phase change material (NeOPCM) for improved exhaust waste heat recovery process. The exergy is an effective method to estimate the quantity and quality of energy recovered from the CI engine and stored in the LHTS unit. The results show that nearly 82% of the energy from the engine exhaust is successfully recovered and stored in a heat exchanger with NeOPCM based LHTS unit. The thermodynamic balance of the exergy and energy for the complete system is calibrated and represented by applying the respective data from the Sankey heat flow balance diagrams. The maximum percentages of the energy and exergy saved from the diesel fuel by the LHTS unit using NeOPCM combined with heat exchanger are nearly 24% and 41% more than those of the virgin paraffin wax.

The leafhoppers comprise by far the largest family within the Hemiptera, with approximately 19,500 described species in over 40 subfamilies (Oman et al. 1990) of which the subfamily Cicadellinae comprises around 2,400 species in around 330 genera. The name “sharpshooter” for this group of xylemfeeding leafhoppers has increasingly been used especially in the USA. They are among the largest and most brightly coloured of the leafhoppers. Some species are important vectors of the xylem-limited bacterium Xylella fastidiosa, which affects both citrus trees in Brazil as well as grapevines in southern USA. The Cicadellinae, as currently defined, was revised by David Young (1915–1991) in three remarkable volumes (Young 1968a, 1977a, 1986a). The publication of these works has enabled the evaluation and description of additional genera and species, primarily by researchers in Brazil and China. The availability of these taxonomic monographs and subsequent publications has made the Cicadellinae a relatively well-known group. In 2004 a project was started, funded by UK-based Leverhulme Trust, which has enabled a compilation of digital images of Cicadellinae. This paper is a brief review of the project in the context of the history of taxonomic work on this group of leafhoppers over the past 150 years. Abbreviations for Institutions discussed in text BMNH The Natural History Museum, London, UK HNHM Hungarian Museum of Natural History, Budapest, Hungary MMBC Brno, Czech Republic MNHN Museum National d’Histoire Naturelle, Paris, France NCSU North Carolina State University Insect Collection, Raleigh, North Carolina, USA NHRS Naturhistoriska riksmuseet, Stockholm, Sweden NMW Naturhistorisches Museum Wien, Vienna, Austria USNM National Museum of Natural History, [formerly, United States National Museum], Washington, DC, USA ZMHB Museum fur Naturkunde der HumboldtUniversitat, Berlin, Germany

Phylogenetic analysis can be conducted using a variety of methods, generally classified as distancebased or character-based approaches. Patterns found through phylogenetic analysis of human mitochondrial DNA (mtDNA) sequences have revealed a wealth of information in such disparate fields as the human evolution; the movement of human lineages throughout history (phylogeography); and the susceptibility of certain groups to devastating diseases. Forensic mtDNA analysis has also benefited from the use of these methods. Phylogenetic assessment of forensic mtDNA databases has revealed a consistency with published data at a depth of analysis that is not attainable with basic population genetic methods. The detailed characteristics of specific sites within a mtDNA sequence are best assessed using phylogenetic methods. These studies have identified the most informative sites for individual differentiation, while also providing quality assurance metrics to apply to individual mtDNA profiles or entire databases. Such a level of evaluation and understanding enhances the interpretation of forensic casework.

Larval therapy, the therapeutic use of blowfly larvae to treat chronic wounds, is primarily used in debridement. There are, however, gaps in current knowledge of the optimal clinical application of the therapy and mechanisms of action in the debridement process. Using an artificial assay, two studies were undertaken to investigate these aspects of larval debridement by Lucilia sericata Meigen (Diptera: Calliphoridae); the first studied the effects of the density of larvae on tissue digestion and larval mass, and the second considered the effects on the same parameters of incorporating protease inhibitors into the feeding substrate. The total mass of tissue digested increased with larval density until saturation was observed at 5.0-7.5 larvae/cm(2) . This range was considered optimal as lower doses resulted in the removal of less tissue and higher doses offered no additional tissue removal and appeared to exacerbate competition for feeding. In the second study, increased protease inhibitor concentration led to significant decreases in tissue digestion and larval mass, suggesting that serine proteases, particularly trypsin, may play major roles in larval digestion. Such information is important in elucidating the main constituents that make up larval digestive products and may be significant in the development of new therapies.

Gymnasts' bone mineral characteristics are generally not known before starting their sport. Prepubertal females who enrolled in beginning artistic gymnastics (n = 65) had lower bone mineral than controls (n = 78). However, 2 years of gymnastics participation versus no participation led to a significantly greater accrual of forearm bone area and lumbar spine areal BMD. Introduction: The skeletal response to exercise in children compared with adults is heightened because of the high bone turnover rate and the ability of bone to change its size and shape. Whereas child gymnasts generally have greater rates of bone mineral accrual compared with nongymnasts, it is unknown if some of these skeletal advantages are present before the onset of training or are caused entirely by training. Materials and Methods: Changes in bone area (BA; cm2), BMC (g), and areal BMD (aBMD; g/cm2) over 24 months were examined in prepubertal females, 4–8 years of age, who selected to perform recreational gymnastics (GYM; n = 65), nongymnastic activities, or no organized activity (CON; n = 78). Participants had essentially no lifetime history of organized athletic participation (

Background The Block98 food frequency questionnaire (FFQ) has been validated for dietary assessment of usual intakes in adults, but not in children. Objective To assess the agreement of the Block98 FFQ and 3-day diet records for measuring dietary intakes in young girls. Subjects/setting Healthy 4- to 9-year-old girls (N=61; 6.5±1.6 years) were recruited from the Athens/Clarke county area in Georgia. Design Dietary intakes were measured using the Block98 FFQ and 3-day diet records, with nutrient analysis of the 3-day diet records conducted using the Food Processor computer program (ESHA; version 7.21, 1998, ESHA Research, Salem, OR). The Block98 FFQ was completed by a trained interviewer and parent, with input from the child, if able. Food models and portion size pictures were used to increase reporting accuracy. Statistical analysis Paired sample t tests and simple regression were conducted to determine whether the two diet instruments reported similar values for energy and macronutrients. Results Block98 FFQ overestimated intakes from 3-day diet records for energy (2,180±692 vs 1,749±328 kcal), protein (68.3±25.9 vs 57.9±14.8 g/day), carbohydrate (298.7±97.0 vs 244.7±46.1 g/day) and fat (83.6±30.5 vs 62.3±14.7 g/day) ( P r =0.40 to 0.55). Applications/conclusions The Block98 FFQ agreed weakly to moderately with the 3-day diet records, and resulted in consistently higher intakes of all nutrients. These findings suggest that additional work is needed to develop a FFQ that reflects young children's energy and macronutrient intakes.

Objective: The primary objective of this investigation was to compare body images of 54 girls (4-8 years old) who were beginning their first gymnastics class to 54 age-matched (� 1 year) and % body fat-matched (� 3%) girls not participating in gymnastics. Method: Rat- ings of actual and ideal body size and a computed measure of body dissatisfaction (actual minus ideal) were obtained. Body composition was measured with dual-energy x-ray absorptiometry. Results: Girls beginning gymnastics did not differ significantly from controls on (meanSD) actual (2.2 � 1.4 vs. 2.1 � 1.4), ideal (1.8 � 1.3 vs. 1.8 � 1.5), or body dissatisfaction (0.39 � 1.8 vs. 0.26 � 1.4) scores. Discussion: Body images of 4-8-year-old girls beginning their first artistic gymnastics class do not differ from non-gymnast controls matched on age and % body fat. This observation casts doubt on the idea that young girls who are dissatisfied with their body and want to be smaller are more likely to enroll in gymnastics classes than girls without this type of body dissatisfaction. # 2003 by Wiley Periodicals, Inc. Int J Eat Disord 34: 244-250, 2003.

Leptin is secreted by adipose tissue and thought to regulate appetite at the central level. Several studies have explored the central nervous system (CNS) entry of this peptide across the blood-brain and blood-cerebrospinal fluid (CSF) barriers in parallel, but this is the first to explore the transport kinetics of leptin across the choroid plexus (blood-CSF barrier) in isolation from the blood-brain barrier (BBB). This is important as the presence of both barriers can lead to ambiguous results from transport studies. The model used was the isolated Ringer perfused sheep choroid plexus. The steady-state extraction of [(125)I]leptin (7.5 pmol l(-1)) at the blood face of the choroid plexus was 21.1+/-5.7%, which was greater than extraction of the extracellular marker, giving a net cellular uptake for [(125)I]leptin (14.0+/-3.7%). In addition, trichloroacetic acid precipitable [(125)I] was detected in newly formed CSF, indicating intact protein transfer across the blood-CSF barrier. Human plasma concentrations of leptin are reported to be 0.5 nM. Experiments using 0.5 nM leptin in the Ringer produced a concentration of leptin in the CSF of 12 pM (similar to that measured in humans). [(125)I]Leptin uptake at the blood-plexus interface using the single-circulation paired tracer dilution technique (uptake in60 s) indicated the presence of a saturable transport system, which followed Michaelis-Menten-type kinetics (K(m)=16.3+/-1.8 nM, V(max)=41.2+/-1.4 pmol min(-1) g(-1)), and a non-saturable component (K(d)=0.065+/-0.002 ml min(-1) g(-1)). In addition, secretion of new CSF by the choroid plexuses was significantly decreased with leptin present. This study indicates that leptin transport at the blood-CSF barrier is via saturable and non-saturable mechanisms and that the choroid plexus is involved in the regulation of leptin availability to the brain.

This paper discusses participate concentration and size distribution data gathered using the University of Missouri-Rolla Mobile Aerosol Sampling System (UMR-MASS), and used to investigate the southern extent of the eastern end of the North Atlantic Flight Corridor (NAFC) during project Pollution From Aircraft Emissions in the North Atlantic Flight Corridor/Subsonic Assessment (SASS) Ozone and Nitrogen Oxide Experiment (POLINAT 2/SONEX) from September 19 to October 23, 1997. The analysis presented in this paper focuses on “the corridor effect,” or enhancement of pollutants by jet aircraft combustion events. To investigate the phenomena, both vertical and horizontal profiles of the corridor, and regions immediately adjacent to the corridor, were performed. The profiles showed a time-dependent enhancement of particulates within the corridor, and a nonvolatile (with respect to thermal volatilization at 300°C) aerosol enhancement at corridor altitudes by a factor of 3.6. The southern extent of the North Atlantic Flight Corridor was established from a four flight average of the particulate data and yielded a boundary near 42.5°N during the study period. A size distribution analysis of the nonvolatile particulates revealed an enhancement in the

Thin, coherently strained, films of SiGe were deposited on Si(001) in the Stranski-Krastanow (SK) growth mode to form small, faceted, dislocation-free-three-dimensional (3D) islands. The number density of these islands was determined as functions of SiGe alloy composition, growth rate, and substrate temperature during growth. From these experiments, the classical model of 3D island nucleation and growth yields an approximate activation energy for diffusion of Ge dimers on a Ge covered Si(001) surface of 0.70 eV. The dependence of the 3D-island number density on growth rate cannot be understood without modifying the classical model to account for the wetting layer present in SK systems. Heteroepitaxial strain is not included in the classical model of island nucleation and growth. A simple linear elastic model that fits the data is developed that predicts the island number density is proportional to the inverse square of the Ge mole fraction in the alloy plus a constant.

Purpose To assess the screening efficacy and practical use of two portable devices to detect moderate to severe visual field loss rapidly in population screening. Methods Henson visual field analysis and Damato campimetry for glaucoma were performed in a healthy adult population, to determine false-positive rates; in established glaucoma patients and suspects, to determine false-negative rates; and in a general adult population, to assess practical use in actual screenings. Results There were no false-positive test failures among the 82 normal subjects who completed the Henson two-step screening. Eighty of 83 normal subjects passed Damato campimetry, resulting in a false-positive rate of 3.6%. Among 83 glaucoma suspects and patients, the Henson test identified 49 (84%) of 58 subjects whose full-threshold fields from Humphrey perimetry were abnormal, 38 (97%) of 39 of whom had moderate to severe visual field loss. The Damato campimeter detected 55 (81%) of 68 subjects with any pathologic loss on full-threshold visual fields, 44 (92%) of 48 of whom had moderate to severe visual field loss. Among 1,278 subjects tested in general population screenings, 55 subjects (4.3%) failed either or both tests. Conclusions The Henson visual field analyzer can discriminate moderately to severely diseased from normal visual fields with high sensitivity and specificity. The Damato campimeter can reliably detect moderate to severe visual field loss with a tolerably low false-positive rate. To overcome the weakness of glaucoma screening by tonometry alone, some forms of visual field testing may be acceptably brief (cost effective) and accurate (sensitive and specific).

The Hammer Down gold prospect occurs in an accretionary tectonic setting in the Paleozoic Appalachian orogen. It has many geologic and geochemical features in common with other shear-hosted, mesothermal gold deposits. The gold prospect is located about 25 km to the east of an exposed continental-oceanic suture zone and is near a major fault (the Green Bay fault) of regional extent. The main mineralized zones consist of structurally controlled quartz veins with abundant pyrite, chalcopyrite, sphalerite, and carbonate, hosted by volcanic and sedimentary rocks of the Ordovician Catchers Pond Group. Gold-bearing veins postdate a regional subgreenschist metamorphism and an early phase of deformation. Mineralization occurred synchronously with a locally intense S 2 fabric within narrow brittle-ductile high strain zones in, and adjacent to, Early Silurian felsic porphyry dikes. Carbonate and chlorite alteration is widespread and, in part, predates the mineralization; however, there is increasing chloritization near the gold-bearing zones and the mineralized veins contain abundant carbonate. Strong sericite-pyrite-rutile hydrothermal alteration is restricted to narrow zones adjacent to veins. Isotopic compositions of quartz (delta 18 O =11.4 + or - 0.7%) and carbonate (delta 13 C =-6.2 + or - 0.7%) from gold-bearing veins at Hammer Down are typical of shear-hosted, mesothermal gold deposits of Archean and younger age. Oxygen isotope thermometry using quartz, chlorite, and muscovite yields temperatures of vein formation between 245 degrees and 320 degrees C. The ore-forming fluids have calculated delta 18 O and delta D values between 1.1 and 5.8 and -36 and -54 per mil, respectively, and are interpreted to be of mixed origin, dominantly from a metamorphic reservoir with a small component of low 18 O meteoric water. In the Hammer Down area, felsic tuff in the host arc-related sequence, the Catchers Pond Group, has an igneous U-Pb zircon age of 480 (super +4) (sub -3) Ma. This allochthonous sequence is intruded by felsic dikes which are correlative with granodiorite of the Burlington Intrusive Suite, a major regional unit of the eastern Baie Verte...

The teleost fishes are among the earliest evolutionary lineages to have an Ig heavy chain (IgH) locus whose organization approximates that of mammals. To understand transcriptional control of the IgH locus in a teleost fish and to gain insight into the evolution of the control elements, the enhancer activity in the IgH locus of the channel catfish, Ictalurus punctatus, was investigated. Segments of the locus extending from upstream of the proximal JH gene to 2.5 kb downstream of the second transmembrane (TM2) exon of the mu gene were tested in transient transfection expression assays in murine myeloma and T cell lines, and in catfish B lymphoblastoid, monocyte-like, and putative T cell lines. In marked contrast to mammals, no enhancer activity was observed in the catfish JH to C mu intron, but strong enhancer activity (approaching that of the murine IgH intronic enhancer) was identified in a 1.8-kb segment that included the TM2 exon. This catfish enhancer was active in a B lineage-specific manner in both catfish and murine cells. It was not localized in a small core region, but appeared to contain multiple, dispersed cooperative elements rich in octamer- and mu E5-related motifs. Although the catfish IgH enhancer shares functional characteristics with the mammalian IgH intronic and 3' enhancers, its unusual organization does not permit any obvious inferences concerning evolutionary relationships between the catfish enhancer and any one of the murine IgH enhancers.

The establishment of channel catfish long term cloned B cell lines, the first such cell lines from ectothermic vertebrates, is described. These diploid cell lines were developed by in vitro LPS stimulation of B cells from normal channel catfish peripheral blood in the absence of overt attempts to transform or immortalize the cells. The resultant cell lines were cloned and maintained continuously in vitro for more than 12 mo without restimulation, feeder cells, or exogenous factors. Southern blot analyses of the parental cell lines revealed multiple mu-chain gene rearrangements, suggesting a polyclonal origin for the cell lines. Additional evidence for polyclonal development was provided by the demonstration that the parental cell lines transcribed mRNA for all of the six known channel catfish VH gene families. The characterization of several clonal cell lines revealed mRNA expression for both the secreted and membrane forms of the catfish mu-chain; however, the cloned cell lines each expressed only a single VH gene and analysis of the Ig H chain locus was consistent with allelic exclusion having occurred in these cells. Flow cytometry demonstrated that the cloned and uncloned cell lines produced both cytoplasmic and cell surface IgM. This IgM contained only one of the two L chain isotypes of the channel catfish, suggesting preferential L chain usage. Although these cells did not appear morphologically to be plasma cells, they secreted moderate levels of IgM in culture. These cell lines have considerable potential for addressing questions concerning the evolution of B cell function.

Telephone interviews utilizing random digit dialing were conducted in Los Angeles County to assess the public's knowledge of differences between ophthalmologists and optometrists and to determine factors predictive of knowledge status. Knowledge status was determined by performance on a questionnaire specifically designed for this study. Using multiple logistic regression analysis for simultaneous evaluation of potentially predictive factors, higher education, history of prior eye examination as an adult, and history of prior or present contact lens or spectacle wear were associated with scoring as knowledgeable. Predicted probabilities of being knowledgeable and not knowledgeable were presented for all combinations of these predictive variables. Such information may be helpful in guiding public education campaigns regarding eye care.

The results of an evaluation of the fracture tolerance of three components of the thrust vector control servo-actuator for the solid rocket booster of the space shuttle are described. These components were considered as being potentially fracture critical and therefore having the potential to fall short of a desired service life of 80 missions (that is, a service life factor of 4.0 on a basic service life of 20 missions). Detailed stress analysis of the rod end, cylinder, and feedback link components was accomplished by three-dimensional finite-element stress analysis methods. A dynamic structural model of the feedback system was used to determine the dynamic inertia loads and reactions to apply to the finite-element model of the feedback link. Twenty mission stress spectra consisting of lift-off, boost, re-entry, and water impact mission segments were developed for each component based on dynamic loadings. Experimental fracture response data da/dN, K I c , and K c were used for the structural alloys of the actuator components. These alloys were Inconel 718, 17-4 PH (H1025), 6061-T651, 2024-T851 (T351), and A286. Linear fatigue crack growth life and residual strength analyses were performed on the component critical locations using the Forman da/dN equation and CRACKS III computer code. Most components were determined to have the potential of reaching a service life of 80 missions or service life factor of 4.0.

A prospective, randomized, double-masked, and placebo-controlled study was performed to evaluate the effects of a localized and sustained release of mitomycin on the success of glaucoma filtration surgery in rabbits. A bioerodible polymer was used as the drug carrier. Full-thickness filtration surgeries were performed and data from 22 rabbits were collected. One eye received a polymer impregnated with mitomycin (0.02 mg or 0.06 mg), while the fellow eye received a drug-free polymer. Intraocular pressure, bleb survival, and postoperative complications were investigated. Intraocular pressures remained lower for a longer period of time (P less than 0.004) and filtration blebs lasted longer (P less than 0.05) in experimental eyes than in control eyes. Conjunctivitis and sectorial corneal haze occurred more frequently in eyes treated with the higher dosage mitomycin compared with control eyes. The use of mitomycin-C in a polymer delivery system appeared to promote the success of glaucoma filtration surgery in rabbits. With the lower dosage of mitomycin, clinically significant ocular toxicity was not noted.

PURPOSE: To evaluate the safety and efficacy of the Ahmed glaucoma valve implant in patients with glaucoma as a result of Sturge-Weber syndrome. METHODS: Eleven eyes (10 patients) with glaucoma resulting from Sturge-Weber syndrome had placement of an Ahmed glaucoma valve implant from May 1993 to June 1996 at the Jules Stein Eye Institute. Success was defined by intraocular pressure at the last two consecutive visits of less than 21 mm Hg, no additional glaucoma surgery, no expulsive choroidal hemorrhage, and no retinal detachment. RESULTS: Mean intraocular pressure on the first postoperative day was 14.0 mm Hg (SD ± 6.7). The cumulative probability of success was 79% (95% confidence interval [CI], 52% to 100%) at 24 months, 59% (95% CI, 20% to 98%) at 42 months, and 30% (95% CI, 0% to 75%) at 60 months. CONCLUSIONS: On the basis of limited follow-up, the Ahmed glaucoma valve implant appears to be a relatively useful drainage device in eyes with glaucoma resulting from Sturge-Weber syndrome.

Background: Evidence suggests that adults and adolescents throughout the United States are at risk of poor vitamin D status. However, vitamin D concentrations in young American children have not been assessed. Objective: The relations between serum 25-hydroxyvitamin D [25(OH)D] and bone were examined in prepubertal girls. Design: In the present cross-sectional study, serum 25(OH)D concentrationwasassessedin168prepubertalgirlsaged4–8ylivingin the southeastern United States with the use of radioimmunoassay. Bone area, bone mineral content, and areal bone mineral density were measured from total body, lumbar spine, proximal femur, and forearm with dual-energy X-ray absorptiometry. Data were analyzed with analysis of variance, analysis of covariance, stepwise multiple regression, and partial correlations. Results:Themean(SD)serum25(OH)Dwas93.828.1nmol/L (range: 31.1–181.4 nmol/L). In a multiple regression analysis, race and season were the strongest predictors of vitamin D status. The black girls had lower mean 25(OH)D values than did the white girls (P 0.01), and 25(OH)D values were significantly different in the total sample between the seasons (P 0.001), ranging from 74.4 nmol/Lduringthewintermonthsto107nmol/Lduringthesummer. After adjustment for season, age, race, and body mass index, 25(OH)Dvalueswerenegativelycorrelatedwithforearmbonemineral content (r 0.18; P 0.02). Conclusions:Unlikepriorreportsofadultsandadolescentslivingin the southeastern United States, vitamin D status was adequate in the children of the present study. 25(OH)D concentrations were not positively associated with higher bone mineral. Am J Clin Nutr 2006;83:75–81.

The positive outcomes of drinking citrus juice, as well as the biological responses to specific nutrients found in juice, have been researched extensively. This chapter summarizes the role citrus juice plays in providing important nutrients and bioactive compounds to the diet. It also summarizes the relationship of these components to various health benefits.

The performance, yield, and reliability of GaAs ICs (integrated circuits) fabricated on OMCVD (organometallic chemical-vapor-deposition)-grown GaAs-on-Si substrates are described. These substrates were used to fabricate MSI-level digital ICs (integrated circuits) in a manufacturing environment. They were processed together with LEC (liquid-encapsulated Czochralski)-grown GaAs wafers to provide a direct comparison with bulk material. Initial evaluations of devices and circuits suggest that it is realistic to believe that GaAs-on-Si substrates can be a viable alternative to LEC-grown GaAs materials. In addition, a two-part reliability study has demonstrated that GaAs-on-Si parts have no liabilities in terms of parametric instability or catastrophic failure mechanisms. However, there are epitaxial growth conditions which must be optimized further to obtain performance which is not inferior to bulk GaAs materials. >

The transcriptional enhancer (E(mu)3') of the IgH locus of the channel catfish, Ictalurus punctatus, shows strong B cell-specific activity and differs from the mammalian E(mu) enhancer in both location and structure. It occurs between the mu and delta genes and contains numerous transcription factor binding sites, predominantly octamer and muE5 motifs of consensus and variant sequences. It lacks the classical muA-muE3(CBF)-muB core array of binding motifs seen within mammalian IgH E(mu) enhancers. To determine the functionally important motifs, a series of mutant enhancers was created using sequence-targeted polymerase chain reaction. Whereas the mutation of consensus and variant octamer motifs (individually or in multiples) decreased enhancer function, mutation of a single consensus muE5 motif destroyed the function of this enhancer in mammalian plasmacytomas. Mutation of this consensus muE5 site, combined with mutations of certain octamer sites, destroyed function in catfish B cells. Experiments using artificial enhancers containing multimers of motifs or short regions of the native enhancer suggested that the minimal E(mu)3' enhancer (a) contains a consensus muE5 site and two octamer sites, (b) is B cell-specific, and (c) is active across species. The dependence of an Ig enhancer on sites that bind basic helix-loop-helix and Oct transcription factors has not previously been observed and confirms large differences in structure and function between fish and mammalian IgH enhancers.

The clusterin gene encodes a multi-functional protein that has been identified in different tissues, including a number of different eye tissues, primarily in the mouse and to a much lesser extent in humans. Clusterin has been implicated in a number of cellular processes such as lipid transport, membrane integrity, apoptosis, and neurodegeneration, all of which could be important to the biology of the eye. In the current communication, we provide data that confirms the expression of clusterin in a number of different human eye tissues and establishes the expression profile of this gene in monkey derived eye tissues. The issue that we sought to examine is whether a broad profile of clusterin expression in the eye is consistent in primates (monkey and human).The majority of our study was done using monkey eye tissues. Where possible, we have used human tissues in order to confirm published findings. Northern and western analysis was performed using tissues derived from monkey eyes. In situ hybridization and immunochemistry were carried out on human eye sections.Clusterin mRNA is expressed in primate lens, cornea, limbus, sclera, orbital muscle, ciliary body, retina, RPE/choroid, and RPE cells in culture. Western analysis revealed that two major groups of clusterin exist in the eye, a high molecular weight group (100 kDa) and a second group consisting of at least five clusterin species that are all approximately 80 kDa. Analysis of conditioned media from RPE cells cultured on permeable supports suggests that different forms of clusterin display alternative patterns of secretion.Clusterin is expressed in a broad range of eye tissues in both human and monkey, suggesting that this is a characteristic feature in primates. We demonstrate for the first time that a diverse number of clusterin isoforms were observed in monkey eye tissues by western analysis. Meanwhile, the molecular size of clusterin mRNA detected in the array of tissues are identical in size, suggesting that the nature of the diversity in clusterin forms is due to post-translational modifications. In addition, new insights were made in defining clusterin expression in ciliary body, cornea, and the retinal pigment epithelium.

Recent studies have suggested that vascular endothelial growth factor (VEGF), in addition to its proangiogenic properties, also functions as a survival factor for endothelial cells. The authors hypothesized that inhibition of VEGF activity by blockade of VEGF receptor-2 (R-2) function prevents angiogenesis and decreases tumor growth in colon carcinoma liver metastases.Spleens of mice were injected with human colon carcinoma cells producing liver metastases. After 7 days of tumor growth, groups of mice received either antibody to VEGFR-2 (DC101) or phosphate-buffered saline (control). In a follow-up experiment, a similar treatment regimen was followed except that mice were sacrificed at 1-week intervals to assess the time course of endothelial cell and tumor cell apoptosis.After 21 days of therapy, the authors observed a significant decrease in vessel counts in liver metastases from human colon carcinoma in nude mice after therapy with VEGFR-2 antibody. Tumor cell apoptosis was increased significantly in the tumors of mice receiving DC101. Temporal studies with immunofluorescent double staining for the microvasculature and apoptotic cells revealed an increase in endothelial cell apoptosis that preceded an increase in tumor cell apoptosis. In vitro, treatment of human umbilical vein endothelial cells with antibody to VEGFR-2 produced a2.5-fold increase in endothelial cell apoptosis.Therapy targeting the VEGFR-2 inhibited tumor growth in a murine model of colon carcinoma liver metastasis. Surprisingly, this therapy did not only inhibit angiogenesis but also led to endothelial cell death. These findings suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for tumor endothelial cells in liver metastases from colon carcinoma.

The objectives of this study were to isolate several rat liver epithelial cell clones containing the human bcl-2 and myc/bcl-2 genes in order to study their potential cooperative effect on neoplastic transformation and gap junction-mediated intercellular communication (GJIC) and to test the hypothesis that the loss of GJIC leads to tumorigenesis. Using anchorage-independent growth as a surrogate marker for neoplastic transformation, we transfected both normal rat liver epithelial cells, WB-F344, and a WB-F344 cell line overexpressing v-myc with human bcl-2 cDNA. Those cell lines that only expressed v-myc or human bcl-2 were unable to form colonies in soft agar. However, those cell lines that overexpressed both v-myc and human bcl-2 showed varying ability to form colonies in soft agar, which did not correlate with their human bcl-2 expression level. In order to test if there was a correlation between cell line growth in soft agar and the ability to communicate through gap junctions, we performed scrape load dye transfer and fluorescence recovery after photobleaching assays. Our results show that v-myc and human bcl-2 can cooperate in the transformation of normal cells, but the degree to which the cells are transformed is dependent on the cells' ability to communicate through gap junctions.

The patient's perspective of his or her own health status as it relates to functioning and well-being is referred to as health-related quality of life. Various generic and ophthalmology-specific survey instruments have been used to gain an understanding of patient-oriented health status in patients with cataract or with glaucoma. Improvement in vision-targeted quality of life has been shown following cataract surgery; however, an improvement in self-perceived overall health status following cataract surgery has not been established. Increasing severity of glaucoma has been shown to be negatively related to vision-targeted quality of life; the relationship between increasing severity of glaucoma and overall self-perceived health status is inconclusive. Integration of the concepts of health-related quality of life into clinical practice will require the development of better measurement instruments that can demonstrate notable outcome advantages for patients.

Increased vascular endothelial growth factor (VEGF) expression is associated with colon cancer metastases. We hypothesized that inhibition of VEGF receptor activity could inhibit colon cancer liver metastases. BALB/c mice underwent splenic injection with CT-26 colon cancer cells to generate metastases. Mice received daily i.p. injections of vehicle, tyrosine kinase inhibitor for Flk-1/KDR (SU5416) or tyrosine kinase inhibitor for VEGF, basic fibroblast growth factor, and platelet-derived growth factor receptors (SU6668). SU5416 and SU6668 respectively inhibited metastases (48.1% and 55.3%), microvessel formation (42.0% and 36.2%), and cell proliferation (24.4% and 27.3%) and increased tumor cell (by 2.6- and 4.3-fold) and endothelial cell (by 18.6- and 81.4-fold) apoptosis (P0.001). VEGF receptor inhibitors increased endothelial cell apoptosis, suggesting that VEGF may serve as an endothelial survival factor.

We report analyses obtained from 135 implant cases retrieved from humans and submitted to the American Academy of Implant Dentistry Research Foundation--Medical College of Georgia Implant Retrieval Center. The undecalcified samples were embedded in polymethyl-methacrylate and examined with scanning electron microscopy and with routine light via polarized or Nomarski microscopy. Cases included both orthopedic and dental implants as well as entire mandibles obtained at autopsy. Significant numbers of submitted implants had substantial amounts of adhered bone, which permitted evaluation of human bone remodeling to osseointegrated implants. These implants failed because of implant fracture. As has been observed in animal studies, an interdigitating canaliculi network provided communication between interfacial osteocytes and osteocytes deeper within the remodeled osteonal and trabecular bone. Significant numbers of osseointegrated fractured hydroxyapatite-coated dental implants demonstrated the adequate serviceability of these implants prior to biomaterial fracture. In contrast, the hydroxyapatite coating was dissociated from retrieved orthopedic implants, leading to extensive cup loosening and case failure. Caution is advised for the use of hydroxyapatite-coated acetabular implants. This study therefore underscores the need for evaluation of failed human dental and orthopedic implants. Correlations can be drawn between human retrieval and experimental animal studies.

Apoptosis is a counterbalance to mechanisms of cell proliferation and is critically important in regulation of the immune system, development, and normal tissue homeostasis. Mammalian signal transduction pathways affecting apoptosis are more complex than their counterparts in the nematode Caenorhabditis elegans, a valuable model system that has provided powerful initial insights into key molecules regulating apoptosis. Despite this complexity, substantial progress has been made in recent years towards defining the nature and detail of signalling pathways bringing about apoptosis in mammalian cells. In particular, the identity and precise substrate specificities of a large family of caspase enzymes, implicated as critical components of the apoptotic machinery, have been defined. In addition, the mechanism by which the cell surface Fas receptor mediates induction of apoptosis, via activation of caspases, has recently been elucidated. A prominent role for mitochondria in cell death pathways has also recently emerged, a clear theme being that mitochondria can trigger degradative events by the release of apoptogenic proteins (e.g., cytochrome c) from the intermembrane space to the cytosol. This review focuses on recent progress in these areas and discusses integration of this knowledge in our overall understanding of the processes that control apoptosis.

The growth and metastasis of cancer directly correlates with tumor angiogenesis. A better understanding of the expression of regulatory factors controlling angiogenesis is important in exploiting this process therapeutically. Our present study demonstrates that small tumors (3-4 mm in diameter) express more basic fibroblast growth factor (bFGF) and interleukin 8 (IL-8) than large tumors (10 mm in diameter), whereas more vascular endothelial growth factor (VEGF) is expressed in large tumors. Immunostaining showed a heterogeneous distribution of angiogenic factors within the tumor; expression of bFGF and IL-8 was highest on the periphery of a large tumor, where cell division is maximum. VEGF expression was higher in the center of the tumor. In vitro studies demonstrated that sparse cultures of tumor cells expressed higher levels of bFGF and IL-8 than confluent cultures. In contrast, the expression of bFGF and IL-8 was not diminished in tumor cells growing on confluent monolayers of normal cells. VEGF expression was upregulated by cell density irrespective of contact with tumor cells or normal cells. These results demonstrate that the expression of different angiogenic factors in tumor cells can be regulated by their proximity to other tumor cells or host cells.

Poor foetal and neonatal nutrition may impair normal pancreatic β -cell development and predispose to diabetes in later life. We investigate here the nature of the pancreatic β -cell dysfunction in sucrose-fed adult offspring malnourished during the foetal-neonatal period and examine glucose metabolism and the generation of signals involved in the secretory mechanism. In islets from sucrose-fed previously malnourished rats, rates of glucose utilisation (production of 3 H 2 O) and oxidation (production of 14 CO 2 ), at 2, 6 and 10 mM glucose, were not lower than those of controls. ATP concentrations in islets from previously malnourished rats fed sucrose at 2 and 10 mM glucose were similar to those of controls. Glucose-stimulated insulin release was impaired (by 49–55%) in islets from these animals as was the response to keto-isocaproate (by 70%) and tolbutamide (by 70%). Under conditions in which ATP-sensitive K + channels were clamped open (40 mM K + and diazoxide), glucose-stimulated insulin release in islets from previously malnourished rats fed sucrose was reduced. These findings show that defects in insulin secretion in islets isolated from previously malnourished animals are located in both ATP-sensitive K + channel dependent and independent pathways. They do not involve alterations in the early steps of glucose handling in the β -cell, including glucose metabolism and ATP generation.

The ability to identify individual human hosts based on analyses of blood recovered from the digestive tract of hematophagous arthropods has been a long-term pursuit in both medical and forensic entomology. Blood meal individualization techniques can bring important advancements to studies of vector-borne disease epidemiology. Forensically, these analyses may aid in assailant identification in violent crime cases where blood-feeding insects or their excreta are recovered from victims or at crime scenes. Successful isolation, amplification, and sequencing of human mitochondrial DNA obtained from adult human crab lice fed on human volunteers are reported. Adult lice were removed from recruited volunteers frequenting inner city health clinics. Live lice were killed by freezing and subsequently air dried at ambient temperature. A saliva sample was obtained from each volunteer and served as a DNA reference sample. Volunteers were afforded free, approved pediculosis treatment. Individual lice were subsequently processed using procedures developed for the extraction of mitochondrial DNA from human hair, teeth, and bone. The resulting DNA was amplified by the polymerase chain reaction and sequenced. Our results point to valuable avenues for future entomological research.

The Ig heavy chain enhancer of the channel catfish (Ictalurus punctatus) has an unusual position and structure, being found in the 3' region of the mu gene and containing eight functional octamer motifs of consensus (ATGCAAAT) and variant sequences. The presence of multiple octamer motifs suggests that an Oct2 homologue may play an important role in driving expression of the Ig heavy chain locus in a teleost fish. To test this hypothesis, two catfish Oct2 cDNAs (alpha and beta) were cloned by screening a catfish B cell cDNA library. Catfish Oct2 alpha and beta isoforms are derived by alternative RNA splicing; as determined by Southern analysis, Oct2 is a single copy gene. In comparisons with mammalian Oct2, the catfish Oct2 isoforms show high sequence conservation in their N-terminal regions and POU domains, but extensive divergence in their C-terminal regions. Catfish Oct2 a and beta are tissue restricted, bind both consensus and variant octamer motifs, and activate transcription in both catfish and murine cells. In contrast, mouse Oct2 activated transcription in mouse but not catfish cells. Catfish Oct2 beta is a more potent transcriptional activator than Oct2 alpha. In transient expression assays, catfish Oct2 beta showed a marked preference for the octamer variant, ATGtAAAT, which occurs twice in the catfish enhancer. Mouse Oct2 also showed increased activity with the variant octamer when tested in mouse B cells. Gel-shift analysis competition assays indicated that catfish Oct2 binds the consensus octamer motif with an apparently higher affinity than it does the variant motif.

Back problems associated with work have become expensive, indeed the most expensive musculoskeletal problem for Western societies [7, 17, 21, 48]. The back is so expensive because it is the most common cause of disability awards for people in the United States of America for persons under 45 years of age [17]. Although the expense is most attributable to disability and worker’s compensation in the industrial context, back problems seem almost unavoidable by the age of 50 and are the most common reason for a doctor’s appointment after the common cold [18]. Many have recommended approaches to reduce the impact but have had little influence on outcon [35].

Since its introduction, PCR has become a widely-used, routine technique in forensic laboratories. A number of PCR protocols that were developed originally are now being replaced by more powerful approaches, particularly those based on multiplex amplification of short tandem repeat (STR) loci. One alternative from of multiplex PCR amplification, called Sequential Multiplex Amplification (SMA), was designed to amplify a single locus and then recover and reuse the remaining genomic DNA as a template for subsequent PCR. The SMA process could be repeated several times. SMA has proven to be useful in typing genomic DNA contained in stored PCR samples and analyzing samples of limited quality and/or quantity for multiple loci. The efficacy of the use of SMA for actual typing of casework samples permitted typing for a second locus 98.11% of the samples considered; 70.75% were typeable for a third locus, and 16.98% for a fourth locus.