Disorders of Sex Development (DSD): Peer Relations and Psychosocial Well-Being.

Social and emotional development is shaped by familial and extra-familial experiences especially interactions with peers. Children and adolescents with physical, behavioral or developmental differences, such as youth with disorders of sex development (DSD), may not benefit to the same degree as other children and adolescents from experiences with peers. This paper reviews current thinking about the features and effects of experiences with peers and the potential challenges of peer interactions for children and adolescents with DSD. We review findings from studies of adjustment for individuals with DSD. We finish the paper with a brief outline of a research agenda to promote the understanding of adjustment of individuals with DSD.

Characterization of a condensed-phase membrane introduction mass spectrometry (CP-MIMS) interface using a methanol acceptor phase coupled with electrospray ionization for the continuous on-line quantitation of polar, low-volatility analytes at trace levels in complex aqueous samples.

We report the development and application of a capillary hollow fibre membrane interface using methanol as an acceptor phase to deliver target analytes to an electrospray ionization source and a triple quadrupole mass spectrometer. Superior fluid handling systems lead to greater signal stability and membrane integrity for the continuous on-line monitoring of polar and charged analytes in complex aqueous samples with detection limits in the parts-per-trillion to parts-per-billion range. The system can be operated in either a continuous flow or a stopped acceptor flow mode - the latter giving rise to greater sensitivity. We report detection limits, enrichment factors and signal response times for selected analytes with polydimethylsiloxane and Nafion® polymer membrane interfaces. In addition, we demonstrate the use of this interface to detect pharmaceuticals and other contaminants in natural water and artificial urine. The improved sensitivity and analytical response times of our CP-MIMS system make it possible to continuously monitor dynamic chemical systems with temporal resolutions on the order of minutes. Presented is a comparison of the performance of CP-MIMS versus direct infusion electrospray ionization, demonstrating the potential advantages over direct infusion for trace analyte measurements in complex, high ionic strength samples. Furthermore, by continuously flowing a reaction mixture in a closed loop over the interface, we demonstrate the use of the system as an in situ reaction-monitoring platform for the chlorination of a model organic compound in aqueous solution.

Heel bone densitometry: device specific thresholds for the assessment of osteoporosis.

A diagnosis of osteoporosis is facilitated by bone mineral density (BMD) measurement of the lumbar spine and hip using dual energy X-ray absorptiometry (DXA), interpreted in accordance with criteria published by the World Health Organization (WHO). The use of peripheral DXA is growing in primary care and guidance on its use has recently been published by the National Osteoporosis Society (NOS), recommending a triage approach using thresholds specific to each type of peripheral device. However, no data currently exist for the Norland Apollo heel densitometer (Cooper Surgical, Trumbull, USA). 215 women between 50 years and 75 years of age (mean age 64.6 years) referred for hip and spine BMD measurements also had a heel BMD measurement. Device specific upper and lower thresholds were calculated for the Norland Apollo heel densitometer to give a 90% sensitivity and 90% specificity for osteoporosis at the hip or spine. Patients with a heel T-score of above -1.2 are very likely to have normal bone density on axial densitometry, whilst patients with heel T-score of below -2.2 are very likely to have osteoporosis at the hip or spine. Patients whose measurements lie between the thresholds should be referred for axial DXA.

Single-species models for many-species food webs.

Most species live in species-rich food webs; yet, for a century, most mathematical models for population dynamics have included only one or two species. We ask whether such models are relevant to the real world. Two-species population models of an interacting consumer and resource collapse to one-species dynamics when recruitment to the resource population is unrelated to resource abundance, thereby weakening the coupling between consumer and resource. We predict that, in nature, generalist consumers that feed on many species should similarly show one-species dynamics. We test this prediction using cyclic populations, in which it is easier to infer underlying mechanisms, and which are widespread in nature. Here we show that one-species cycles can be distinguished from consumer resource cycles by their periods. We then analyse a large number of time series from cyclic populations in nature and show that almost all cycling, generalist consumers examined have periods that are consistent with one-species dynamics. Thus generalist consumers indeed behave as if they were one-species populations, and a one-species model is a valid representation for generalist population dynamics in many-species food webs.

Breast milk activity during early lactation following maternal 99Tcm macroaggregated albumin lung perfusion scan.

A breast feeding infant may receive a radiation dose from ingestion of breast milk following the administration of a radiopharmaceutical to the mother. The Administration of Radioactive Substances Advisory Committee recommendation to interrupt breast feeding may not necessarily apply in the period of early lactation when colostrum is being produced. Following a lung scan using 99Tcm macroaggregated albumin (MAA) on a patient approximately 15 h post partum, radioactivity within breast milk was measured. Milk was expressed approximately every 4 h during the day and samples were counted. The sample radioactivity concentration peaked at 15 h and decayed monoexponentially (half clearance time was approximately 4.8 h). The estimated effective dose to the infant from ingestion alone, had breast feeding not been interrupted, was approximately 0.02 mSv. These data suggest that interruption to breast feeding may not be necessary following administration of up to the diagnostic reference level of 99Tcm MAA during early lactation.

The discovery of sulfonylated dipeptides as potent VLA-4 antagonists.

Directed screening of a carboxylic acid-containing combinatorial library led to the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic characterization of this series are presented.

Habitat structure and population persistence in an experimental community.

Understanding spatial population dynamics is fundamental for many questions in ecology and conservation. Many theoretical mechanisms have been proposed whereby spatial structure can promote population persistence, in particular for exploiter-victim systems (host-parasite/pathogen, predator-prey) whose interactions are inherently oscillatory and therefore prone to extinction of local populations. Experiments have confirmed that spatial structure can extend persistence, but it has rarely been possible to identify the specific mechanisms involved. Here we use a model-based approach to identify the effects of spatial population processes in experimental systems of bean plants (Phaseolus lunatus), herbivorous mites (Tetranychus urticae) and predatory mites (Phytoseiulus persimilis). On isolated plants, and in a spatially undivided experimental system of 90 plants, prey and predator populations collapsed; however, introducing habitat structure allowed long-term persistence. Using mechanistic models, we determine that spatial population structure did not contribute to persistence, and spatially explicit models are not needed. Rather, habitat structure reduced the success of predators at locating prey outbreaks, allowing between-plant asynchrony of local population cycles due to random colonization events.

Multiple dynamics in a single predator-prey system: experimental effects of food quality.

Recent work with the freshwater zooplankton Daphnia has suggested that the quality of its algal prey can have a significant effect on its demographic rates and life-history patterns. Predator-prey theory linking food quantity and food quality predicts that a single system should be able to display two distinct patterns of population dynamics. One pattern is predicted to have high herbivore and low algal biomass dynamics (high HBD), whereas the other is predicted to have low herbivore and high algal biomass dynamics (low HBD). Despite these predictions and the stoichiometric evidence that many phytoplankton communities may have poor access to food of quality, there have been few tests of whether a dynamic predator-prey system can display both of these distinct patterns. Here we report, to the authors' knowledge, the first evidence for two dynamical patterns, as predicted by theory, in a single predator-prey system. We show that the high HBD is a result of food quantity effects and that the low HBD is a result of food quality effects, which are maintained by phosphorus limitation in the predator. These results provide an important link between the known effects of nutrient limitation in herbivores and the significance of prey quality in predator-prey population dynamics in natural zooplankton communities.

Autonomy and relatedness in family interactions with depressed adolescents.

This study investigated family interaction patterns associated with adolescent depression. Twenty adolescent-mother dyads with clinically depressed adolescents participated in the study. Twenty dyads with externalizing youths and 20 nonclinic dyads were included as controls. Dimensions of autonomy and relatedness were rated during a videotaped mother-adolescent problem-solving task. Adolescent perceptions of parent attachment were also evaluated. Results indicated that depressed adolescents and their mothers did not differ in their behavior compared with nonclinic adolescents. Dyads with externalizing adolescents showed the highest impairment in autonomy and relatedness. Depressed adolescents perceived the quality of their relationships with their parents to be impaired relative to nonclinic dyads, as did externalizing adolescents.

Psychosocial development in adolescents with Turner syndrome.

Turner syndrome is a genetic condition in which part or all of the second X chromosome is missing. Our goal in this study was to examine the psychosocial adjustment of a sample of adolescent girls with Turner syndrome. Subjects included 122 girls with a diagnosis of Turner syndrome (TS) and a control group of 108 girls with no genetic disorder or chronic illness. Subjects were 13 to 18 years of age. A battery of questionnaires assessing social, academic, school, and behavioral functioning was administered. TS girls were seen as having significantly more problems in terms of social relationships and school progress and were more likely to meet criteria for attention-deficit hyperactivity disorder than control girls. The TS girls were also rated by a parent as less socially competent (e.g., fewer friends, less time with friends) than the control group. Social difficulties appear to be an area of vulnerability for TS girls. Counseling individuals with Turner syndrome and their families about the need to carefully develop and nurture social skills and relationships may prove useful in advancing the social adaptation of these young women.

Nutritional constraints in terrestrial and freshwater food webs.

Biological and environmental contrasts between aquatic and terrestrial systems have hindered analyses of community and ecosystem structure across Earth's diverse habitats. Ecological stoichiometry provides an integrative approach for such analyses, as all organisms are composed of the same major elements (C, N, P) whose balance affects production, nutrient cycling, and food-web dynamics. Here we show both similarities and differences in the C:N:P ratios of primary producers (autotrophs) and invertebrate primary consumers (herbivores) across habitats. Terrestrial food webs are built on an extremely nutrient-poor autotroph base with C:P and C:N ratios higher than in lake particulate matter, although the N:P ratios are nearly identical. Terrestrial herbivores (insects) and their freshwater counterparts (zooplankton) are nutrient-rich and indistinguishable in C:N:P stoichiometry. In both lakes and terrestrial systems, herbivores should have low growth efficiencies (10-30%) when consuming autotrophs with typical carbon-to-nutrient ratios. These stoichiometric constraints on herbivore growth appear to be qualitatively similar and widespread in both environments.

Family reinforcement of illness behavior: a comparison of adolescents with chronic fatigue syndrome, juvenile arthritis, and healthy controls.

Parental encouragement of illness behavior is hypothesized to correlate with psychosocial dysfunction in adolescents with chronic illness. To explore this hypothesis, adolescents aged 11 to 17 years with chronic fatigue syndrome (CFS) (n = 10), juvenile rheumatoid arthritis (JRA) (n = 16), and healthy adolescents (n = 14) were recruited for the study. Measures included the Achenbach parent and youth self report forms, the Family Adaptability and Cohesion Evaluation Scale-II (FACES II), the Children's Depression Rating Scale, and number of days absent from school. The Illness Behavior Encouragement Scale (IBES) generated measures of parental reinforcement of illness behavior. As predicted, the teens with CFS scored statistically higher on measures of depression, total competence, and number of days of school missed in the previous 6 months (mean = 40). Children with JRA scored significantly lower than the CFS group on the measure of parental reinforcement of illness behavior. The healthy group produced intermediate scores. Results and implications for future clinical and research activity are discussed.

Neurodevelopmental and psychosocial aspects of Turner syndrome.

Turner syndrome (TS) is the complex phenotype of human females with complete or partial absence of the second sex chromosome, or monosomy X. A characteristic neurocognitive and psychosocial profile has also been described in TS females. Typically, specific deficits in visual-spatial/perceptual abilities, nonverbal memory function, motor function, executive function, and attentional abilities occur in TS children and adults of varying races and socioeconomic status. TS-associated psychosocial difficulties occur in the areas of maturity and social skills. We hypothesize that a subset of the neurocognitive deficits (visual-spatial/perceptual abilities) are genetically determined and result from abnormal expression of one or more X chromosome genes. In addition, a different subset of these neurocognitive deficits (memory, reaction time, and speeded motor function) result from estrogen deficiency and are at least somewhat reversible with estrogen treatment. The TS-associated psychosocial problems are most likely linked to these core neurocognitive deficits and do not reflect a separate and independent component of the syndrome. Turner syndrome research has progressed significantly over the last decade. The field has moved from descriptive reports based on single individuals or small clinical samples to the use of experimental designs with larger, more diverse and representative samples. This degree of variability among individuals with Turner syndrome in all domains (karyotype or genetic constitution, physical attributes, neurocognitive and social functioning) suggests the need to identify risk and protective factors contributing to the heterogeneity in the phenotype. Active education about TS and participation in patient advocacy groups such as the Turner Syndrome Society of the United States (http://www. turner-syndrome-us.org/) has provided new information for TS adults and families as well as a supportive peer group. MRDD Research Reviews 2000;6:135-141.

Pattern Formation and the Spatial Scale of Interaction between Predators and Their Prey.

We study interactions of predators and prey that are characterized by a scale difference in their use of space. Prey are assumed to occupy patches, forming a metapopulation with low migration among patches. Predators are homogeneously distributed over these patches, due to broad-scale foraging behavior or long-range juvenile dispersal. The predator population thus exerts a globally uniform predation pressure on the prey subpopulations. Under these conditions a nonlinear predator functional response depending on local prey density leads to multiple equilibria that can occur for the same parameter values. These equilibria differ in the fraction of prey patches that are (nearly) empty. Equilibria with a larger fraction of empty prey patches are more stable. The system tends to approach equilibria with a sufficiently high number of empty prey patches, so that local and global population dynamics are stable. If unstable dynamics are observed at all, the fluctuations in local prey density exhibit predictable characteristics. Our main conclusion is that a nonlinear functional response of the predator to local prey density can induce the formation of static patterns in prey density and, hence, lead to stable local and global dynamics. It is shown that these results are sufficiently general to carry over to situations in which prey migration between patches does occur or the spatial domain occupied by the prey population is continuous instead of subdivided into patches. Copyright 1998 Academic Press.

Changes in esophageal function after vertical banded gastroplasty as demonstrated by esophageal scintigraphy.

BACKGROUND: The effects of surgery for morbid obesity on the function of the upper gastrointestinal (GI) tract are of interest to bariatric surgeons. This study was undertaken to determine any changes in esophageal function, following vertical banded gastroplasty (VBG) in morbidly obese patients, as detected by esophageal scintigraphy. METHODS: Ten consecutive morbidly obese patients (six female and four male) underwent preoperative esophageal scintigraphy and upper GI endoscopy. These investigations were repeated 12 months after VBG to coincide with expected appreciable weight reduction. The results were tabulated together with body mass indices, crude weights and percentage excess weight lost. RESULTS: Before VBG one patient gave a history of mild heartburn, one had mild dyspepsia and the remaining eight patients had no GI symptoms. No patient had a hiatus hernia or endoscopic evidence of reflux esophagitis. Preoperatively all patients had abnormal scintiscans. The abnormalities were esophageal retention (all) and intraesophageal reflux (five out of 10 patients). Gastroesophageal reflux was not identified in any patient. Postoperatively scintiscans were normal or improved in six out of 10 patients and unchanged in four out of 10 patients. In three patients the scans were normal and three showed overall improvement in esophageal function, although in one of these latter patients gastroesophageal reflux was observed. CONCLUSIONS: In this series of morbidly obese patients, esophageal function as assessed by scintigraphy was abnormal. Following VBG it improved in six out of 10 patients and was unchanged in four out of 10. However, in one patient, who had shown an overall improvement in esophageal function, gastroesophageal reflux was demonstrated when it had not been seen preoperatively. This was asymptomatic. Thus, adverse changes in esophageal function after VBG were uncommon.

Oestrogens and psychological well-being.

The last decade has seen increased interest in the role of hormones, including oestrogens, not only in regulating growth, sexual development and reproduction but in maintaining a sense of psychological well-being. Episodes of change in oestrogen levels, whether increasing or decreasing, are high-risk periods for the emergence of psychological symptoms in some women. This may be due to a 'kindling effect' for women with previous psychological disturbance, an effect on circadian rhythm activity and therefore altered neurovegetative functions, or an effect on central rhythmic functioning between the hypothalamus and the cerebral cortex, all mediated by effects on neurotransmitter systems. Data supporting these hypotheses come from animal studies as well as converging research in several areas including the study of psychological side-effects of oral contraceptives, the study of mood and cognitive disturbances related to the menstrual cycle, the studies of states of hormonal change such as pregnancy and the menopause and, of course, studies of women with psychiatric disorders such as major depression, seasonal affective disorder and dementia. Improvement in such symptoms via hormonal therapies or other interventions will probably lead to better quality of life for women and may actually impede the deterioration associated with ageing and certain medical illnesses. Current data support a relationship between oestrogen and psychological well-being.

Expression and immunoaffinity purification of human inducible nitric-oxide synthase. Inhibition studies with 2-amino-5,6-dihydro-4H-1,3-thiazine.

Recombinant human inducible nitric-oxide synthase (rH-iNOS) was expressed in the baculovirus system and purified by a novel immunoaffinity column. rH-iNOS and its native counterpart from cytokine-stimulated primary hepatocytes exhibited similar molecular mass of 130 kDa on SDS-polyacrylamide gel electrophoresis, recognition by antipeptide antibodies, specific activities, and IC50 values for inhibitors. The active dimeric form exhibited a specific activity range of 114-260 nmol/min/mg at 37 degrees C and contained 1.15 +/- 0.04 mol of calmodulin/monomer. The enzyme exhibited a Soret lambdamax at 396 nm with a shoulder at 460 nm and contained 0. 28-0.64 mol of heme/monomer. Dithionite reduction under CO yielded an absorbance maximum at 446 nm, indicating a P450-type heme. Imidazole induced a type II difference spectrum, reversible by L-Arg. 2-Amino-5,6-dihydro-4H-1,3-thiazine (ADT) was competitive versus L-Arg (Ki = 22.6 +/- 1.9 nM), reversed the type II difference spectrum induced by imidazole (Kd = 17.7 nM), and altered the CO-ferrous absorbance of rH-iNOS. L-Arg did not perturb the CO-ferrous adduct directly, but it partially reversed the ADT-induced absorbance shift, indicating that both bind similarly to the protein but interact differently with the heme.

Speciation of arsenic oxides using laser desorption/ionization time-of-flight mass spectrometry.

Positive and negative ion mass spectra of arsenic trioxide (As2O3) and arsenic pentaoxide (As2O5) have been obtained by single-step laser desorption/ionization time-of-flight mass spectrometry. Pulsed UV radiation at 266 nm was used for the simultaneous desorption and ionization of the solid sample. High-mass cluster ions that are unique to the oxidation state of each oxide sample appear in the negative ion mass spectra. The As2O3 produces As3O5-, while the As2O5 yields As3O8-. The formation of unique negative cluster ions presents the capability for arsenic oxidation state speciation by laser desorption/ionization mass spectrometry. The ability of time-of-flight mass spectrometry to examine the relative amounts of each arsenic oxide present in a series of mixtures is discussed. Application of our speciation technique to a model incinerator sample is demonstrated.

Laser desorption/ionization time-of-flight mass spectrometry of nitrated polycyclic aromatic hydrocarbons.

Mass spectra of four nitrated polycyclic aromatic hydrocarbons (nitro-PAHs), 9-nitroanthracene, 1-nitropyrene, 2-nitro-9-fluorenone, and 2-nitrofluorene, have been investigated using single-step laser desorption/ionization time-of-flight mass spectrometry. Pulsed UV radiation at 266 or 213 nm was used for desorption and ionization of solid samples deposited on an aluminum probe. The positive molecular ion which was observed for each nitro-PAH was of greater relative intensity when 213 nm radiation was used. A strong [M - NO]+ peak was observed in all spectra, and an intense NO+ signal accompanied the [M - NO]+ signal when 213 nm was used but was only weakly present when 266 nm was used. Comparison of the various spectra suggests that nitro-PAHs undergo an excited state nitro-nitrite rearrangement, followed by loss of NO. Multiphoton ionization of the NO fragment appears to be the principal route of formation of NO+ during laser desorption/ionization when 213 nm radiation is used. The presence of the carbonyl group in 2-nitro-9-fluorenone leads to unique and prominent fragments involving losses of CO from the carbonyl bridge.

Active-site structure analysis of recombinant human inducible nitric oxide synthase using imidazole.

Nitric oxide synthase catalyzes the pyridine nucleotide-dependent oxidation of L-arginine to nitric oxide and L-citrulline. It is a specialized cytochrome P450 monooxygenase that is sensitive to inhibition by imidazole. Steady-state kinetic studies on recombinant human inducible nitric oxide synthase (rH-iNOS) demonstrate that imidazole and 1-phenylimidazole are competitive and reversible inhibitors versus L-arginine. Structure-activity relationship and pH dependence studies on the inhibition suggest that the neutral form of imidazole may be the preferred species and that the only modifications allowed without the loss of inhibition are at the N-1 position of imidazole. Optical spectrophotometric studies of rH-iNOS with imidazole and 1-phenylimidazole yielded type II difference spectra exhibiting Kd values of 63 +/- 2 and 28 +/- 3 microM, respectively. These values were in good agreement with the steady-state Ki of 95 +/- 10 and 38 +/- 4 microM, respectively, and confirms the site of binding is at the sixth axial ligand of the heme. Imidazole (2.2 mM) also perturbed the Kd of L-arginine from 3.03 +/- 0.45 to 209 +/- 10 microM. The observed increase in the Kd for L-arginine is consistent with imidazole being a competitive inhibitor versus L-arginine. The IC50 values of imidazole and 1-phenylimidazole were lower in the absence of exogenous BH4, and both inhibitors also competitively inhibited the BH4-dependent activation of the enzyme. These data taken together suggest that the L-arginine, dioxygen, and the BH4 binding sites are in close proximity in rH-iNOS. Furthermore, these studies demonstrate the usefulness of imidazole compounds as active site probes for recombinant human iNOS.