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Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.

Two neonates were identified at age 48 h by expanded newborn screening, with abnormal methionine and tyrosine concentrations, which were confirmed on repeat samples. Evidence of previously unsuspected liver disease was found at recall, and there was radiological and biochemical evidence of severe liver disease with hepatic synthetic failure. After inborn errors of metabolism (IEMs) were excluded, both were considered to have neonatal haemochromatosis, on the basis of raised ferritin, iron saturation, and very high α-fetoprotein and confirmed by a mildly hyperferritinaemic sibling in the first case, and raised ferritin and iron saturation in the second. However, it was not feasible to obtain tissue confirmation as the requirement for early therapy precluded biopsy. The babies were treated with antioxidants and iron-chelating agents, and the coagulopathy and hypoalbuminaemia were corrected. Both made a complete recovery and remain well after follow-up. Newborn screening programmes could consider advising clinicians, when tyrosine and methionine values are elevated, that once IEMs are excluded liver disease from other causes must be sought. Neonatal haemochromatosis is an example of one such disease that is potentially treatable.

Extensive results from the commissioning phase of PUEO, the adaptive optics instrument adaptor for the Canada‐France‐Hawaii Telescope (CFHT), are presented and discussed. Analyses of more than 750 images recorded with a CCD and a near‐IR camera on 16 nights in wavelengths from B to H are used to derive the properties of the compensated wavefront and images in a variety of conditions. The performance characteristics of the system are analyzed and presented in several ways, in terms of delivered Strehl ratios, full width half‐maxima (FWHM), and quantities describing the improvements of both. A qualitative description is given of how the properties of the corrected images result from the structure function of the compensated phase. Under median seeing conditions, PUEO delivers essentially diffraction‐limited images at H and K and images with FWHM ∼ 0 \documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepac...

Primordial binaries in globular clusters are important both because their properties are an integral part of the description of the stellar population and because they can strongly influence the dynamical evolution of the cluster (see Hut, this volume).

Investigation of nutrient stimulation of two gut hormones GIP (glucose dependent insulotropic polypeptide) and GLP-1(7-36)amide (the active truncated form of glucagon-like peptide-1) is made difficult by the differential control of gastric emptying. Direct nutrient infusion into the duodenum was therefore carried out on three female pigs. The infusates consisted of saline (0.85 g or 1.7 g/100 ml); glucose (20 g or 40 g/100 ml); fat (30 g or 60 g/500 ml) and glucose/fat (20 g and 30 g or 40 g and 60 g per 1000 ml). Plasma glucose levels were elevated as expected by glucose or glucose/fat infusions, and they were not affected by the presence of fat in the infusate. Insulin secretion was stimulated in the presence of glucose or glucose/fat. Plasma triacylglycerol was elevated following fat and glucose/fat infusions. The greatest stimulus for GIP secretion was glucose/fat (P < 0.05); fat alone was a poor stimulus for GIP secretion, but glucose was a potent stimulus. GLP-1(7-36)amide was moderately stimulated by glucose and markedly stimulated by fat and glucose/fat infusions (P < 0.05). We conclude that, in pigs, dual nutrient infusion of glucose/fat is a strong stimulus for both GIP and GLP-1(7-36)amide secretion. The hormones therefore have the potential to play an important physiological role, both in the stimulation of insulin secretion and in adipose tissue metabolism in pigs.

We describe a detailed physical map of human chromosome 11, extending from the distal part of p13 through the entirety of p14 to proximal p15.1. The primary level of mapping is based on chromosome breakpoints that divide the region into 20 intervals. At higher resolution YACs cover approximately 12 Mb of the region, and in many places overlapping cosmids are ordered in contiguous arrays. The map incorporates 18 known genes, including precise localization of the GTF2H1 gene encoding the 62-kDa subunit of TFIIH. We have also localized four expressed sequences of unknown function. The physical map incorporates genetic markers that allow relationships between physical and genetic distance to be examined, and similarly includes markers from a radiation hybrid map of 11. The cytogenetic location of cosmids has been examined on high-resolution banded chromosomes by fluorescence in situ hybridization, and FLpter values have been determined. The map therefore fully integrates physical, genic, genetic, and cytogenetic information and should provide a robust framework for the rapid and accurate assignment of new markers at a high level of resolution in this region of 11p.

The coordination of the Military, Diplomatic and Economic/Development levers of power, the so-called “hard” and “soft” powers, to bring about the strategic aims of governments, supported by Non-Governmental Organisations and international organisations, is commonly known as the Comprehensive Approach (CA). The CA is now part of both NATO and UK military doctrine and concepts development. This article describes how medical branch HQ Allied Rapid Reaction Corp, as part of the HQs work to operationalise the CA, has sought and developed training opportunities to improve individual skill-sets to enable the branch to better contribute to the CA process.

To compare a gram protein exchange system (1g=50-mg Phenylalanine) with a unit exchange system (1unit=15-mg Phenylalanine) and its effect on the blood Phenylalanine (Phe) levels and acceptance in the dietary management for children and adolescents with Phenylketonuria.In Phase One, participants were randomised to continue counting Phe unit exchanges (n=8) or changed to counting gram protein exchanges (n=10), using a new diet chart developed in-house. Foods containing less than 20mg Phe per serve were now considered "free." Interim data analysis confirmed no significant deterioration in Phe levels of the study group and the control group was changed to protein counting.In Phase Two, 18 participants were educated to use an updated version of the in-house diet chart - in this version foods containing less than 50mg Phe per serve were considered "free."In both phases, attitudes to PKU and its management were evaluated at baseline and 6months. Phenylalanine and tyrosine levels were measured from filter paper blood spots by tandem mass spectrometry.Phase One: Phe levels over 6months were comparable to pre-study levels (mean Phe pre 366μmol/L+/- 169, mean Phe post change=388μmol/L+/- 160).Phase Two: Four participants had a significant improvement in blood Phe levels, nine showed no significant change and one participant's levels were significantly higher. There was incomplete data on four participants. All participants preferred the freer diet chart.Protein exchanges (foods containing less than 50mg Phe/serve uncounted) are an alternative method of measuring Phe intake in the dietary management of Phenylketonuria.

Strategies to reduce the relatively high incidence of death and disease in young animals must be based on an understanding of the particular metabolic requirements in the period from birth to weaning. In this period, substrate availability and the pathways of substrate utilization differ from those of the foetus and of the adult. Metabolic requirements must be met from the energy stores laid down before birth and from the nutrients present in colostrum and milk. The young animal has a large glucose demand and after exhaustion of hepatic glycogen reserves this must be met by gluconeogenesis. Initiation of gluconeogenesis requires concomitant oxidation of fatty acids, either derived from adipose tissue or from the diet. The young animal is particularly susceptible to hypothermia. Non-shivering thermogenesis in brown adipose tissue uses fatty acids to uncouple oxidation from phosphorylation and also as the major oxidative substrate. In addition, non-shivering thermogenesis is dependent on a minimum concentration of circulating glucose. Shivering thermogenesis is initially fuelled by oxidation of intra-muscular glycogen and then primarily by dietary fat. Growth of white adipose tissue by deposition of dietary fatty acids is an important feature of the metabolism of many species before weaning and this may have several survival advantages.

The DAO/CFHT image stabilizing camera HRHR-Cam was used to search for closely spaced images resulting from gravitational lensing by foreground galaxies in a sample of 101 bright quasars. No convincing objects were found. Several widely-separated (1 – 6 arc-sec) point source companions were detected but half of these are known to be stars, and it is argued that the remainder are also likely to be stars. A slight excess of galaxy companions to the quasars is found when compared to a control sample of stars, but the difference is not statistically significant (galaxy companions to 17 quasars were found, similar companions were noted around 12 stars).

The somatic cell hybrid C121, with chromosome 7 as its sole human component, arose when mouse macrophages were immortalized by fusion with SV40-transformed human fibroblasts. The transforming SV40 genomes are integrated at 7q31-7q35. We show that hybrids with a reduced chromosome 7 component, but which retain markers linked to the cystic fibrosis locus, can be generated by direct in vivo tumor selection or following chromosome-mediated gene transfer and SV40-mediated cellular transformation. Our methods for chromosome fragmentation and fine-structure mapping can now be applied to the substantial number of SV40-transformed human cell lines, with independent chromosomal integration sites, already available. Our results also suggest that expression of human epidermal growth factor receptor augments the tumorigenic potential of the SV40-transformed C121 hybrid.

The paper presents a brief outline of the rationale behind the use of non invasive functional imaging and of the features that any imaging technique should display in order to make a substantial contribution to the search of the brain mechanisms responsible for cognitive functions. One such technique, magnetic source imaging (MSI), that meets these specifications, is described in more detail. Advantages of MSI include the capacity to provide direct measures of regional neurophysiological activity, a millisecond range temporal resolution, and the capacity to provide images of brain activity on an individual basis. We then describe applications of MSI to the study of brain mechanisms involved in various language functions such as oral comprehension and reading. Among these applications, the accuracy of MSI protocols in determining hemispheric dominance for language functions and in identifying the precise location and extent language specific cortex (Wernicke s area) has been verified through comparison with standard invasive techniques (Wada procedure and electrocortical stimulation mapping) in over 60 consecutive cases. In another series of studies we combined data from MSI and direct cortical stimulation to determine the role of temporoparietal areas in phonological analysis of spoken language and in phonological decoding of print. Finally, we have used MSI to gain unique insights into the brain mechanisms that support reading in developmental reading disability.Results from over 21 children diagnosed with this disorder suggest that impaired reading is associated with aberrant functional connections between temporal and temporoparietal areas of the left hemisphere that are normally engaged in reading.

Plants make a variety of compounds in response to environmental stress, many of which function as antioxidants when consumed. The plants' own defences against oxidative stress can be used for your benefit, prolonging your life by acquiring their protection. By eating plenty of vegetables and fruit, you may help to significantly reduce the risk of many age-related degenerative diseases.

Children with congenital hydrocephalus, children with attention deficit-hyperactivity disorder, and normal controls were evaluated with measures of focused attention (Visual Orienting and Detection Task), sustained attention (continuous performance test), and attention shifting (Wisconsin Card Sorting Test). Components from these tasks have been linked to attention systems mediated by anterior or posterior brain networks. Children with congenital hydrocephalus showed an inability to focus and shift attention, which specifically implicated impairment of the disengage and move components of the posterior brain attention system. Children with attention deficit-hyperactivity disorder displayed the expected performance patterns on measures of focused attention once their difficulties with sustained attention were taken into account. However, they showed problems with shifting and sustaining attention, which are commonly associated with the anterior brain attention system.

Although natural weaning in the pig occurs at 6 to 8 weeks of age it is common commercial practice to wean at 3 to 4 weeks. This abrupt and early weaning is often associated with a more or less prolonged check in growth, frequent occurrence of gastrointestinal disease and a significant mortality. The transition from a milk diet to a solid diet in the post-weaning period necessitates complex digestive and metabolic adaptations in the piglet. Experiments in small animals have shown that some of the changes brought about by weaning are at least partially controlled by hormones from the adrenal cortex (Henning, 1981).We have investigated the changes that occur in the mucosa of the small intestine and in the pancreas of pigs weaned at 21 days of age. In addition we have investigated the effects of an orally administered synthetic glucocorticoid (dexamethasone; DEX) given before weaning, on the development of the intestine and pancreas.Two pigs from each of six litters were killed at 18 days of age, half of the remaining pigs were given DEX (0.4mg/kg ) suspended in agar (0.5%). This dose was divided into four equal aliquots and given by stomach tube on days 19 and 20. Controls received an equivalent volume of agar. Pigs were weaned at 21 days, two control and two DEX treated pigs were killed on the day of weaning and at 28, 35 and 42 days. After weaning pigs were allowed ad libitum access to a commercial starter diet.

The period of growth from parturition to weaning is a time of rapid fat deposition in many species. In the pig, body fat increases from about 10 g/kg at birth to 150 to 200 g/kg by 21 days of age (Wood and Groves 1965; Whittemore, Aumaitre and Williams, 1978). An adequate reserve of adipose tissue may be crucial to ensure health and survival, for example during the period of low food intake frequently observed after weaning.It is likely that the nutrient composition of milk and the hormonal signals elicited by milk consumption play an important rôle in stimulating fat deposition. We have investigated the effects of milk ingestion on release of the gastrointestinal hormones GIP (gastric inhibitory peptide) and GLP-1 (glucagon-like peptide one). In addition, we have studied the effects of these hormones on fatty acid synthesis in vitro.Explants (0.4 to 0.6 mg) of adipose tissue were obtained from three anatomical sites of an 18-day-old pig fasted for 12 h. The explants were pre-incubated for 90 min and then incubated in the presence of hormones and [14C] acetate (0.2μCi/ml). Triacylglycerols were extracted from the explants and following saponification, fatty acids were separated and radioactivity counted.

Children with learning and attention disorders commonly present with symptoms of both types of disorders. In many children, this co-occurrence represents comorbid disorders that are separate but overlapping. Because of comorbidity, the presence of one disorder signals the need to evaluate for the other disorders. Evaluation and treatment approaches must address both disorders when present.

A paired-associate learning (PAL) test was administered to 22 community volunteers without disruptive disorders and 197 children (7.5-13.5 years-old) presenting with the inattentive and combined subtypes of attention-deficit/hyperactivity disorder (ADHD) either in combination with or without oppositional defiant disorder (ODD). Participants were screened for learning disorders. In comparison to non-ADHD participants, children with ADHD achieved worse PAL and made errors rated as more acoustically and less semantically similar to the correct paired associates. These deficits were not related to hyperactivity-impulsivity or comorbid ODD. These results suggest that ADHD children are less competent at PAL and use less efficient learning strategies than their non-ADHD peers.

We previously reported on cognitive and respiratory factors in a series of infants with achondroplasia (ACH). We now present the results of neuropsychological evaluation and magnetic resonance imaging in 16 school-age children with ACH, 7 of whom had been included as infants in our previous report. We examined the neuroanatomic and cognitive status of this sample, as well as the predictive stability of the prior infant assessment. Seventeen normally developing children of average stature and 21 preterm children with arrested (compensated, unshunted) hydrocephalus constituted the comparison groups. Brain volumes of children with ACH were significantly larger than those of the comparison groups. In addition, children with ACH exhibited kinking of the medulla and neuroanatomic abnormalities consistent with arrested hydrocephalus, including enlarged ventricles and hypoplasia of the corpus callosum. Cognitive abilities at school age were average, although mild deficits were seen on visual-spatial tasks, similar to those obtained by the hydrocephalic comparison group. Only gross motor coordination deficits distinguished the ACH group from the hydrocephalic controls. Infant assessment overestimated later school-age IQ scores in those infants with ACH who scored above average. These findings point to generally preserved cognitive skills in selected children with ACH at early school age, although children with ACH should be evaluated individually as they are at risk for cognitive, academic, and motor deficits.

Children with arrested, shunted, and no hydrocephalus were compared on verbal and nonverbal memory tasks assessing multiple components of memory. A gradient of severity was hypothesized, with the shunted hydrocephalus group expected to exhibit the most significant memory impairments and the arrested group expected to perform more poorly than children with no hydrocephalus. Etiologies of prematurity, spina bifida, and aqueductal stenosis were represented by 157 participants. Results supported the hypothesis; the shunted hydrocephalus group performed poorer on all memory measures. Differences for the arrested group were less frequently statistically significant relative to children with no hydrocephalus. Irrespective of etiology, the shunted hydrocephalus group exhibited a pattern of performance suggestive of encoding and retrieval deficits on both verbal and nonverbal tasks, showing a pervasive disturbance of memory processes.

Our objective was to review the Australasian experience of X-linked adrenoleukodystrophy (ALD), to compare the spectrum of disease seen in Australasia with previously published data from elsewhere, and to assess the reliability of carrier testing. Study design was a retrospective review of records collected over a 15-year period, the setting was an international referral laboratory for the study of metabolic disease, and the subjects were all known cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000. Of 95 affected males, 51 had cerebral adrenoleukodystrophy, 24 had adrenomyeloneuropathy, 15 had Addison's disease only, and 5 remained asymptomatic when last examined. However, the distribution of phenotypes among newly diagnosed patients has changed substantially over the last 15 years, with cerebral forms of the disease forming a decreasing proportion of new diagnoses. The measurement of plasma very long chain fatty acids (VLCFAs) alone detects 93% of women who can be proven to be carriers. The addition of genetic linkage studies or assay of VLCFAs in cultured fibroblasts improved this detection rate to the point that there were no obligate carriers who could not be detected using a combination of two or more techniques.

To further investigate the usefulness of 3 purported measures of executive function (EF) in head injured children, we administered the Twenty Questions Test (TQT), Tower of London (TOL), and the Wisconsin Card Sorting Test (WCST) to 151 children who had sustained a closed head injury (CHI) of varying severity about 3 years earlier. In addition, we tested 89 normal controls. Fifty-seven of the patients were included in a longitudinal study that compared performance at 3 months and 36 months. All of the head injured children underwent magnetic resonance imaging for investigational purposes. Severity of CHI, as defined by the lowest Glasgow Coma Scale (GCS) score, affected performance on all 3 EF measures. Focal lesion volume incremented prediction of performance on TOL and WCST, but not TQT. Moderate intercorrelations of the test variables were obtained. Although all three EF measures depicted changes in performance over 3 years, a ceiling effect detracted from the sensitivity of the TOL to the impact of CHI on development. Implications of the findings for clinical applications are discussed.

Heparan sulfate proteoglycans have been implicated in the presentation of a number of secreted signaling molecules to their signal-transducing receptors. We have characterized a gene trap mutation in the gene encoding a heparan sulfate biosynthetic enzyme, heparan sulfate 2-sulfotransferase (HS2ST). Transgenic mice were generated from embryonic stem cells harboring this insertion.lacZ reporter gene activity in heterozygous embryos demonstrates that the gene is expressed differentially during embryogenesis, presumably directing dynamic changes in heparan sulfate structure. Moreover, mice homozygous for the Hs2st gene trap allele die in the neonatal period, exhibiting bilateral renal agenesis and defects of the eye and the skeleton. Analysis of kidney development in Hs2st mutants reveals that the gene is not required for two early events—ureteric bud outgrowth from the Wolffian duct and initial induction of Pax-2 expression in the metanephric mesenchyme. It is required, however, for mesenchymal condensation around the ureteric bud and initiation of branching morphogenesis. Because 2-O-sulfation has been shown to influence the functional interactions of ligands with heparan sulfate in vitro, we discuss the possibility that the Hs2st mutant phenotype is a consequence of compromised interactions between growth factors and their signal-transducing receptors. These data provide the first genetic evidence that the regulated synthesis of differentially glycosylated proteoglycans can affect morphogenesis during vertebrate development.

This study linked 2 experimental paradigms for the analytic study of reading that heretofore have been used separately. Measures on a lexical decision task designed to isolate phonological effects in the identification of printed words were examined in young adults. The results were related to previously obtained measures of brain activation patterns for these participants derived from functional magnetic resonance imaging (fMRI). The fMRI measures were taken as the participants performed tasks that were designed to isolate orthographic, phonological, and lexical-semantic processes in reading. Individual differences in the magnitude of phonological effects in word recognition, as indicated by spelling-to-sound regularity effects on lexical decision latencies and by sensitivity to stimulus length effects, were strongly related to differences in the degree of hemispheric lateralization in 2 cortical regions.

We report here the prenatal diagnosis of Smith-Lemli-Opitz (SLO) syndrome in the first trimester by direct measurement of 7-dehydrocholesterol (7-DHC) in a chorionic villus (CV) biopsy. The proband was diagnosed clinically at birth and the diagnosis was confirmed biochemically by demonstrating elevated 7-DHC in plasma. The family pursued prenatal diagnosis in their fourth, fifth, and sixth pregnancies. The fourth pregnancy spontaneously miscarried at 9 weeks' gestation. Analysis in both direct and cultured curetting tissue (identified as similar to CV tissue) showed an abnormal tissue neutral sterol pattern with an elevated 7-DHC concentration. The fifth pregnancy also miscarried spontaneously at 9 weeks but no tissue of unequivocal fetal origin could be identified to allow biochemical investigation. In the sixth pregnancy, ultrasound examination at the time of CV sampling showed a thickened nuchal fold. Direct analysis of the CV sample revealed elevated levels of 7-DHC consistent with the diagnosis of SLO. The pregnancy was terminated and both fetal tissue and cultured fetal cells showed marked increases in 7-DHC, confirming the prenatal diagnosis.

In this chapter we have reviewed the diagnosis and management of attention deficit disorder, focusing particularly on the role of stimulant therapy in ADHD. Hisorical review suggests that ADHD has roots that extend back almost a century. The definition of ADHD is based on inclusion and exclusion criteria that are established by history and reflect behavioral concerns. Attention-deficit/hyperactivity disorder is a chronic disorder affecting the child's home, school, and community life. The primary symptoms of the disorder manifest a developmental pattern: activity diminishes while attentional deficits persist. Major sources of concern are the secondary and often more resistant problems of learning difficulties, behavioral problems, lack of peer acceptance, and low self-esteem. An often frustrating and perplexing characteristic of the disorder is its marked variability-over time, across situations, and within the same child and similar situations. Educational management represents an important priority and often forms the cornerstone of all other therapies, nonpharmacologic or pharmacologic. Cognitive-behavioral therapies represent the most widely used alternative to pharmacotherapy. Although the effects of CBT alone are disappointing, recent studies suggest that such therapies may provide a useful adjunct to pharmacotherapy and may be helpful when children are tapered off medication. Psychotherapy, or a combination of psychotherapy and medication (termed multimodality therapy), may also be useful. Pharmacotherapy for ADHD originated almost 60 years ago, and at this time the ameliorative effects of medications in ADHD are well established. The general skepticism of experienced clinicians, coupled with a climate where parents are reluctant to medicare children, serves to limit their use except where indicated. Although the effects of stimulants on attention and activity seem well established, effects on cognition, conduct, and social behavior are more controversial. Within recent years, a great deal has been learned about the pharmacokinetics of stimulants in children with ADHD, providing a rational basis for administration. It is also clear that side effects are minimal, the most serious being the possibility of the emergence of tics. Whereas stimulants are clearly the most effective agents, other agents, including antidepressants, may also be effective. Recent advances may now provide an opportunity to better understand the neural and molecular basis for ADHD. Recent advances in imaging technology, particularly fMRI, offer an opportunity to examine the neural basis of ADHD, and advances in genetics may provide clues to its etiology.

A catalog of 383 radial velocities for red giants in the globular cluster M22 has been compiled from the literature and from new observations accumulated between 1972 and 1994. This 22-year baseline is the longest available for any sample of globular cluster stars. Using 333 repeat velocities for 109 cluster members, we have carried out a search for spectroscopic binaries with periods in the range 0.2 -- 40 years and with mass ratios between 0.1 and 1.0. Although the velocities for these evolved stars show clear evidence for atmospheric motions, no star is convincingly found to exhibit a velocity variation greater than 7 km/s. By comparing the observed velocity variations to those found in a series of Monte-Carlo simulations, we estimate the cluster binary fraction to be X = 0.01 (circular orbits) and X = 0.03 (thermal orbits). These results are to be compared to the corresponding binary fraction of X = 0.12 for nearby solar-type stars having similar mass ratios and periods. We speculate that both the relative abundances of short- and long-period binaries in globular clusters and the large differences in measured binary fractions for clusters with high binary ionization rates (M22, Omega Cen) compared to those for clusters with low ionization rates (M71, M4, NGC 3201) point to a frequency-period distribution in which soft binaries have been disrupted by stellar encounters. Finally, we note that none of the three CH stars in our survey shows evidence for velocity variations; this is in stark contrast to field CH stars, virtually all of which are binaries. We argue that binaries in M22 which have binding energies similar to field CH stars are unlikely to have been disrupted by stellar encounters and suggest that the cluster CH stars are otherwise normal red giants which lie in the carbon-enriched tail of the cluster metallicity, Comment: 40 pages; TeX and PS figures. Also available at http://www.dao.nrc.ca/DAO/SCIENCE/science.html

Between 1990 and 1992, the status was determined of all of the known Coregonus populations of England and Wales, i.e., Coregonus albula (L.) of Bassenthwaite Lake and Derwentwater, and Coregonus lavaretus (L.) of Brotherswater, Haweswater, Red Tarn, Llyn Tegid and Ullswater. C. albula of Bassenthwaite Lake showed slightly higher growth rates and individual condition than those of Derwentwater, but also displayed signs of inconsistent recruitment in recent years. Growth rates and condition also varied among populations of C. lavaretus, with those of the Llyn Tegid population being particularly low. Recent recruitment was consistent in all populations of this species except those of Haweswater and possibly Brotherswater. The surveys also revealed that the fish communities of several of these lakes had been changed in recent years due to introductions of roach, Rutilus rutilus (L.), and ruffe, Gymnocephalus cernuus (L.).

In view of the pathophysiology and biomechanics of severe closed head injury (CHI) in children, we postulated that the frontal lobes sustain diffuse injury, even in the absence of focal brain lesions detected by magnetic resonance imaging (MRI). This study quantitated the morphological effects of CHI on the frontal lobes in children who sustained head trauma of varying severity. The MRI findings of 14 children who had sustained severe CHIs (Glasgow Coma Scale score ofor = 8) were compared with the findings in a matched group of 14 children having sustained mild head injuries (Glasgow Coma Scale score of 13-15). The patients ranged in age from 5 to 15 years at the time of their MRIs, which were acquired at least 3 months postinjury. MRI findings revealed no focal areas of abnormal signal in the frontal lobes. Volumetric analysis disclosed that the total prefrontal cerebrospinal fluid increased and the gray matter volume decreased in the patients with severe CHI, relative to the mildly injured comparison group. Gray matter volume was also reduced in the orbitofrontal and dorsolateral regions of the brains of children with severe CHI, relative to the children who sustained mild head trauma. These volumetric findings indicate that prefrontal tissue loss occurs after severe CHI in children, even in the absence of focal brain lesions in this area. Nearly two-thirds of the children who sustained severe CHIs were moderately disabled after an average postinjury interval of 3 years or more, whereas 12 of the 14 patients with mild CHIs attained a good recovery (2 were moderately disabled) by the time of study.(ABSTRACT TRUNCATED AT 250 WORDS)

The direct actions of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1(7-36)amide and insulin on lipoprotein lipase activity in explants of rat epididymal adipose tissues were investigated. Lipoprotein lipase was extracted into the incubation medium by heparin release of lipoprotein lipase and measured by fatty acid release from a glyceroltriolein emulsion. Insulin and glucose-dependent insulinotropic polypeptide caused a significant stimulation of lipoprotein lipase activity over a dose range of 0.25-4 nmol/L and 4-8 nmol/L, respectively. Explants incubated in the presence of both insulin and glucose-dependent insulinotropic polypeptide (at 0.5 and 4 nmol/L, respectively) showed levels of lipoprotein lipase activity significantly greater than that seen with either hormone alone. Neither insulin- nor glucose-dependent insulinotropic polypeptide-stimulated lipoprotein lipase was modified by the presence of the antibiotic actinomycin-D in the incubation medium, indicating that these two hormones exert their actions on the pre-existing cellular pool of lipoprotein lipase. Glucagon-like polypeptide-1(7-36)amide, over a dose range of 1-8 nmol/L, did not stimulate lipoprotein lipase activity. This study indicates that glucose-dependent insulinotropic polypeptide, in addition to stimulating insulin secretion, has a direct biological action on adipose tissue and in vivo, together with insulin, may promote lipoprotein lipase activity postprandially.

Expressed sequence tags (ESTs) provide an efficient route to the identification of genes involved in normal development and in disease. PCR amplification of somatic cell hybrid DNAs was used to localise 22 brain-derived ESTs to subregions of human chromosome 11. Problems encountered with the standardised PCR conditions were overcome by optimising the annealing temperatures and the use of “touchdown” PCR. Amplification of the correct target sequence allowed the mapping of 19 ESTs, 8 to the short arm and 11 to the long arm of chromosome 11. No definitive localisation could be determined for the three remaining ESTs.

Neurobehavioral outcome after craniocerebral gunshot wounds was evaluated in a prospective, 3-year, longitudinal follow-up of a consecutive case series of 13 children and adolescents. The younger group was composed of seven children, ages 1.5 to 4 years, and the older group contained six children, ages 5 to 14. Outcome measures included the Glasgow Outcome Scale and neuropsychological assessment of intelligence, language, motor, memory, attention, academic achievement, and adaptive behavior. Glasgow Outcome Scale scores at baseline indicated moderate and severe disabilities in 69 and 23%, respectively. At the 3-year follow-up, 85% had moderate disabilities but only 8% were severely disabled. Significant and persistent neurobehavioral deficits varied with developmental level at the time of cerebral insult. Intellectual functioning was clearly more impaired in children younger than 5 years of age at the time of injury than in older children. Cognitive and motor factors were most closely related to deficits in the younger group. Disability in older children and adolescents was associated with impaired attention, adaptive behavior, and behavioral disturbance. Disabilities appear to be at least as severe in our sample after cerebral gunshot wounds as in our studies of severe pediatric closed-head injury. At the time of follow-up, younger children sustaining gunshot wounds had slightly lower intelligence quotient scores and similar receptive language, expressive language, and gross motor scores compared with children with severe closed-head injury. The older gunshot wound patients were significantly more impaired than patients with severe closed-head injuries on measures of adaptive behavior and attention.(ABSTRACT TRUNCATED AT 250 WORDS)

In the pig, undernutrition in utero causes low birth weight, a decrease in muscle fiber number, and a reduction in postnatal growth rate. The effect on fiber number is mediated via a reduced secondary fiber population. Within a litter of pigs, lighter-weight pigs have probably suffered some deficit in muscle fiber number. In an attempt to improve the number of fibers in the lighter-weight pig fetuses, four maternal feeding regimens were used, one serving as the control. Maternal feed intake was doubled for one of three time periods during pregnancy: 1) d 25 to 50 (HE) immediately before fiber hyperplasia; 2) d 50 to 80 (HL) during fiber hyperplasia; or 3) d 25 to 80 (HT) covering both developmental events. Controls were fed at levels routinely used for pregnant sows on the farm. Sows farrowed normally and pig birth weights were recorded. Estimates were made of total myofiber number, total primary fiber number, and mean secondary:primary fiber number ratio (S:P) for the semitendinosus of each pig at 5 wk postnatal or 80 kg (HT and two control litters only). The progeny of all supplemented sows had a significantly greater mean S:P ratio (P.05), and the HE pigs tended to have a greater number of muscle fibers than control pigs (403,840 +/- 8,197 vs 370,970 +/- 12,720). Postnatal growth rate to 80 kg was also investigated for the HT group of pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Mutation or deletion of the PAX6 gene underlies many cases of aniridia. Three lines of evidence now converge to implicate PAX6 more widely in anterior segment malformations including Peters' anomaly. First, a child with Peters' anomaly is deleted for one copy of PAX6. Second, affected members of a family with dominantly inherited anterior segment malformations, including Peters' anomaly are heterozygous for an R26G mutation in the PAX6 paired box. Third, a proportion of Sey/+ Smalleye mice, heterozygous for a nonsense mutation in murine Pax-6, have an ocular phenotype resembling Peters' anomaly. We therefore propose that a variety of anterior segment anomalies may be associated with PAX6 mutations.

Research on change is complicated by problems of measurement and analysis stemming from a conceptualization of change as a series of accumulating increments and decrements. In contrast, individual growth curves depict change as a continuous process underlying individual performance. These two perspectives are reviewed, and some problems with the use of difference scores in the study of change are clarified. Traditional methods are contrasted with growth curve analysis for the purposes of measuring change and studying its correlates. An illustrative example of the use of growth curves is provided from research on recovery of cognitive function following pediatric closed head injury.

The Children's Orientation and Amnesia Test (COAT) was developed to assess cognition serially during the early stage of recovery from traumatic brain injury in children and adolescents. The norms for the COAT, which is composed of 16 items evaluating general orientation, temporal orientation, and memory, were defined from data obtained from 146 children aged 3 to 15 years. In 37 patients with head injuries, the duration of posttraumatic amnesia, as indicated by the number of days COAT scores were in the impaired range, was significantly related to both verbal and nonverbal memory at the baseline and 6 and 12 months after injury. COAT scores were a better predictor of verbal and nonverbal memory performance than the Glasgow Coma Scale score at 6 and 12 months after the injury. This study shows that the COAT has adequate reliability and validity as a measure of the duration of posttraumatic amnesia in children and adolescents.

We hypothesized that results of previous investigations indicating an increased prevalence of reading disability in boys compared with girls reflected a bias in subject selection. In an epidemiologic sample of 215 girls and 199 boys, we identified two groups of reading-disabled children: research identified and school identified. Results indicated no significant differences in the prevalence of reading disability in research-identified boys compared with research-identified girls in either second (17[8.7%] of 196 boys; 15[6.9%] of 216 girls) or third grade (18[9.0%] of 199 boys; 13[6.0%] of 215 girls). In contrast, school identification resulted in the classification of 27 (13.6%) of 198 boys and seven (3.2%) of 216 girls in second grade and 20 (10.0%) of 199 boys and nine (4.2%) of 215 girls in third grade. Our data indicate that school-identified samples are almost unavoidably subject to a referral bias and that reports of an increased prevalence of reading disability in boys may reflect this bias in ascertainment. These findings caution against relying solely on schools for identification of reading-disabled children.

This study provides a longitudinal follow-up of the behavioral adjustment of 45 children with mild, moderate, and severe closed head injuries. Two measures of behavioral adjustment, the Child Behavior Checklist (CBCL) and the Vineland Adaptive Behavior Scales (VABS), were obtained from a parent at the time of injury and at 6 and 12 months postinjury. The severely injured children obtained significantly poorer VABS scores than children with mild and moderate injuries over the year-long follow-up. In addition, on the CBCL, severely injured children had more school problems and engaged in fewer social activities than mild and moderately injured children. These results show that severe head injury in children was associated with declines in adaptive functioning, whereas scores for children with mild and moderate injuries did not differ, nor did they deviate from average levels at any follow-up interval.

Nine probes were isolated from a human chromosome 1 enriched library and mapped to regions of chromosome 1 using somatic cell hybrid lines. One clone, LR67, which mapped to 1q12----q23 detected a BglI RFLP. This probe, as well as 4 other known chromosome 1 markers, alpha-spectrin, Factor XIIIB, DR10 and DR78, were used for linkage studies in 15 Charcot-Marie-Tooth disease (CMT1) families. Close linkage of CMT1 to any of the 5 markers was not indicated. Total lod scores excluded linkage of CMT1 to LR67 and to DR10 at 5 cM or less, to DR78 at 10 cM or less, alpha-spectrin at 15 cM or less and Factor XIIIB at 20 cM or less. Possible linkage, however, was shown between LR67 and CMT1 at a distance of 30 cM. Also linkage at a distance of 5 cM was detected between this probe and alpha-spectrin.

Patient collapse is a problem requiring rapid and effective management. The Mersey Region strategy for preparing dentists and practice personnel to deal with this situation is to train them by means of practical teaching courses held in the dental surgery. The nature of this course is described.