A comparison of Australian and Canadian calibration coefficients for air kerma and absorbed dose to water for 60Co gamma radiation.

Australian and Canadian calibration coefficients for air kerma and absorbed dose to water for 60Co gamma radiation have been compared using transfer standard ionization chambers of types NE 2561 and NE 2611A. Whilst the primary standards of air kerma are similar, both being thick-walled graphite cavity chambers but employing different methods to evaluate the Awall correction, the primary standards of absorbed dose to water are quite different. The Australian standard is based on measurements made with a graphite calorimeter, whereas the Canadian standard uses a sealed water calorimeter. The comparison result, expressed as a ratio of calibration coefficients R=N(ARPANSA)/N(NRC), is 1.0006 with a combined standard uncertainty of 0.35% for the air kerma standards and 1.0052 with a combined standard uncertainty of 0.47% for the absorbed dose to water standards. This demonstrates the agreement of the Australian and Canadian radiation dosimetry standards. The results are also consistent with independent comparisons of each laboratory with the BIPM reference standards. A 'trilateral' analysis confirms the present determination of the relationship between the standards, within the 0.09% random component of the combined standard uncertainty for the three comparisons.

An open trial of an intensive summer day treatment program for severely overweight adolescents.

This open trial examined the feasibility and usefulness of treating adolescents with a body mass index (BMI) > or =95th percentile in a 6-week day treatment program within a psychiatric outpatient setting. Sixteen adolescents, ages 12-15, attended a 6-week multidisciplinary summer day treatment program. Outcome measures include pre- and post-program assessments of BMI, body fat, laboratory measures, nutritional status, physical activity, mood and eating disorder symptoms, motivation, self-esteem and quality of life. BMI, waist/hip circumferences, blood pressure, heart rate, and body fat did not change significantly from baseline to week 6. Fasting glucose decreased significantly from baseline to week 6, but there were no significant changes in other laboratory measures. The teen-rated feelings subscale of the Peds Quality of Life Scale improved. Self-esteem, as measured by the Rosenberg Self- Esteem Scale, indicated a strong trend towards improvement, and motivation measures also showed a trend for improvement. These findings suggest that a brief, intensive intervention for overweight adolescents may yield meaningful changes in quality of life, self-esteem, and motivation, even in the absence of significant weight loss.

Total energy expenditure as measured by doubly-labeled water in outpatients with bulimia nervosa.

OBJECTIVE: This study measured total energy expenditure (TEE) in symptomatic outpatient women with bulimia nervosa and normal controls. The study aimed to test the conceptual model of bulimia nervosa as an illness characterized by a physiological state of starvation, despite normal weight. METHOD: Total fat and fat-free mass were measured using hydrodensitometry and total energy expenditure was assessed via the doubly-labeled water method, in nine normal weight outpatient females with DSM-III-R bulimia nervosa and ten healthy female controls. RESULTS: Patients and controls were similar in age, body mass index, weight, lean body mass, and levels of exercise and general activity. Patients had an average baseline binge frequency of 14.7 episodes per week and purge frequency of 16.8 times per week, and had been ill for an average of 11.9 years. Group mean TEE did not differ between patients and controls (patients 2380 +/- 482 kcal/day, controls 2368 +/- 515 kcal day). Observed TEE in the bulimic subjects did not differ significantly from TEE predicted on the basis of data from the controls. DISCUSSION: This finding of normal TEE in symptomatic outpatients with bulimia nervosa is consistent with a previous study that found no difference in TEE in a sample of symptomatic inpatients with bulimia nervosa. These data suggest that the energy conserving metabolic adaptations characteristic of semi-starvation do not occur in patients with bulimia nervosa.

Longitudinal relationships between childhood, adolescent, and adult eating disorders.

OBJECTIVE: This study investigates the longitudinal course of eating problems from childhood though adulthood. The following questions are answered: (1) How stable are eating disorder symptoms and diagnoses over a 17-year interval from childhood to adulthood? (2) Do early childhood eating problems predict the occurrence of eating disorders in adulthood? METHOD: An epidemiologically selected sample of approximately 800 children and their mothers received DSM-based structured psychiatric assessments in 1975, 1983, 1985, and 1992. The stability of full DSM diagnostic criteria for anorexia nervosa and bulimia nervosa, symptom scales derived from DSM criteria, and individual symptoms such as binge eating or dieting between early adolescence, late adolescence, and young adulthood was examined. RESULTS: Early adolescent bulimia nervosa is associated with a 9-fold increase in risk for late adolescent bulimia nervosa and a 20-fold increase in risk for adult bulimia nervosa. Late adolescent bulimia nervosa is associated with a 35-fold increase in risk for adult bulimia nervosa. Symptom scale scores for anorexia nervosa and bulimia nervosa correlate in the 0.3 to 0.5 range from early to late adolescence and young adulthood. For both anorexia nervosa and bulimia nervosa, gender, as well as eating symptoms at early and late adolescence, all predict young-adult eating disorder symptoms. Risk factors for the later development of eating disorders comprise eating conflicts, struggles with food, and unpleasant meals in early childhood. CONCLUSION: The presence of eating problems in early childhood or an eating disorder in adolescence confers a strong risk for an eating disorder in young adulthood.

DNA sequencing up to 1300 bases in two hours by capillary electrophoresis with mixed replaceable linear polyacrylamide solutions.

This paper presents results on ultralong read DNA sequencing with relatively short separation times using capillary electrophoresis with replaceable polymer matrixes. In previous work, the effectiveness of mixed replaceable solutions of linear polyacrylamide (LPA) was demonstrated, and 1000 bases were routinely obtained in less than 1 h. Substantially longer read lengths have now been achieved by a combination of improved formulation of LPA mixtures, optimization of temperature and electric field, adjustment of the sequencing reaction, and refinement of the base-caller. The average molar masses of LPA used as DNA separation matrixes were measured by gel permeation chromatography and multiangle laser light scattering. Newly formulated matrixes comprising 0.5% (w/w) 270 kDa and 2% (w/w) 10 or 17 MDa LPA raised the optimum column temperature from 60 to 70 degrees C, increasing the selectivity for large DNA fragments, while maintaining high selectivity for small fragments as well. This improved resolution was further enhanced by reducing the electric field strength from 200 to 125 V/cm. In addition, because sequencing accuracy beyond 1000 bases was diminished by the low signal from G-terminated fragments when the standard reaction protocol for a commercial dye primer kit was used, the amount of these fragments was doubled. Augmenting the base-calling expert system with rules specific for low peak resolution also had a significant effect, contributing slightly less than half of the total increase in read length. With full optimization, this read length reached up to 1300 bases (average 1250) with 98.5% accuracy in 2 h for a single-stranded M13 template.

Automatic comparisons of artificial digits never compared: learning linear ordering relations.

In 2 experiments, participants were trained to perform magnitude decisions, that is, decide which of 2 arbitrary symbols in a pair represented a larger magnitude. The symbols corresponded to locations on an implicit linear scale. Training resulted in a Stroop-like size congruity effect when the participants had to decide which symbol in a pair was physically larger. This effect, showing automaticity of the processing of magnitude relations, was also obtained for pairs never encountered during practice. The implications of these findings for processing of magnitude relations and for theories of automaticity are discussed.

Eating disorders in children and adolescents: pharmacological therapies.

Anorexia nervosa and bulimia nervosa do exist in childhood, frequently have their onset in adolescence, and can result in serious medical and psychiatric sequelae that impede physical, emotional, and behavioral development. Although we use the same Diagnostic and Statistical Manual of Mental Disorders-Version 4 [DSM-IV] definitions to diagnose eating disorders in children, adolescents, and adults, these disorders may be expressed somewhat differently in younger populations, requiring assessment and treatment procedures that are tailored to their developmental needs. Significant advances have been made in recent years in our understanding of treatments for eating disorders in adults, and specifically pharmacological treatments for these disorders. Multiple double-blind, placebo-controlled studies have documented the short-term efficacy of antidepressant medications in bulimia nervosa. While the usefulness of pharmacological treatments for the acute treatment of anorexia nervosa is less clear, recent evidence suggests a role for medication in the relapse-prevention stage of the illness. The majority of the medication trials for the eating disorders have been conducted with adults, and the literature on the pharmacological treatment of children and adolescents with these disorders is very limited. This review article summarizes the current literature on the role of medication in the treatment of anorexia nervosa and bulimia nervosa, with particular emphasis on studies conducted in child and adolescent populations.

Routine DNA sequencing of 1000 bases in less than one hour by capillary electrophoresis with replaceable linear polyacrylamide solutions.

Long, accurate reads are an important factor for high-throughput de novo DNA sequencing. In previous work from this laboratory, a separation matrix of high-weight-average molecular mass (HMM) linear polyacrylamide (LPA) at a concentration of 2% (w/w) was used to separate 1000 bases of DNA sequence in 80 min with an accuracy close to 97% (Carrilho, E.; et al. Anal. Chem. 1996, 68, 3305-3313). In the present work, significantly improved speed and sequencing accuracy have been achieved by further optimization of factors affecting electrophoretic separation and data processing. A replaceable matrix containing a mixture of 2.0% (w/w) HMM (9 MDa) and 0.5% (w/w) low-weight-average molecular mass (50 kDa) LPA was employed to enhance the separation of DNA sequencing fragments in CE. Experimental conditions, such as electric field strength and column temperature, as well as internal diameter of the capillary column, have been optimized for this mixed separation matrix. Under these conditions, in combination with energy-transfer (BigDye) dye-labeled primers for high signal-to-noise ratio and a newly developed expert system for base calling, the electrophoretic separation of 1000 DNA sequencing fragments of both standard (M13mp18) and cloned single-stranded templates from human chromosome 17 could be routinely achieved in less than 55 min, with a base-calling accuracy between 98 and 99%. Identical read length, accuracy, and migration time were achieved in more than 300 consecutive runs in a single column.

A sample purification method for rugged and high-performance DNA sequencing by capillary electrophoresis using replaceable polymer solutions. A. Development of the cleanup protocol.

A method for the cleanup of Sanger DNA sequencing reaction products for capillary electrophoresis analysis with replaceable polymer solutions has been developed. A poly(ether sulfone) ultrafiltration membrane pretreated with linear polyacrylamide was first used to remove template DNA from the sequencing samples. Then, gel filtration in a spin column format (two columns per sample) was employed to decrease the concentration of salts below 10 microM in the sample solution. The method was very reproducible and increased the injected amount of the sequencing fragments 10-50-fold compared to traditional cleanup protocols. Using M13mp18 as template, the resulting cleaned-up single DNA sequencing fragments could routinely be separated to more than 1000 bases with a base-calling accuracy of at least 99% for 800 bases. The method is simple and universal and can be easily automated. In the following paper, a systematic study to determine quantitatively the effects of the sample solution components such as high-mobility ions (e.g., chloride and dideoxynucleotides) and template DNA on the injected amount and separation efficiency of the sequencing fragments is presented.

A sample purification method for rugged and high-performance DNA sequencing by capillary electrophoresis using replaceable polymer solutions. B. Quantitative determination of the role of sample matrix components on sequencing analysis.

In the previous paper, a sample cleanup procedure for DNA sequencing reaction products was developed, in which template DNA was removed by ultrafiltration and the total concentration of salts (chloride and di- and deoxynucleotides) was decreased below 10 microM using gel filtration. In this paper, a quantitative study of the effects of these sample solution components on the injected amount and separation efficiency of the sequencing fragments in capillary electrophoresis is presented. The presence of chloride and deoxynucleotides in a total concentration above 10 microM in the sample solution significantly decreased the amount of DNA sequencing fragments injected into the capillary column. However, the separation efficiency was not affected upon increasing the amount of salt. On the other hand, in the presence of only 0.1 microgram of template in the sample (one-third of the lowest quantity recommended in cycle sequencing) and at very low chloride concentration (approximately 5 microM), the separation efficiency decreased by 70%, and the injected amount of DNA sequencing fragments was 40% lower compared to the sample cleaned by the new purification method. The deleterious effect of template DNA on the separation of sequencing fragments was suppressed in the presence of salt in a concentration above 100 microM in the sample solution. Separately, it was found that both the electric field strength and duration of injection affected the resolution of DNA sequencing fragments when the cleaned up sample solution was used. Separation efficiencies of 15 x 10(6) theoretical plates/m were achieved when the sample was loaded at low electric field, e.g., 25 V/cm for 80 s or less. The results demonstrate that the sample solution components (chloride, deoxynucleotides, template DNA) and injection conditions must be controlled to achieve high performance and rugged DNA sequencing analysis.

Characterization of high molecular mass linear polyacrylamide powder prepared by emulsion polymerization as a replaceable polymer matrix for DNA sequencing by capillary electrophoresis.

In a previous paper, a 2% w/w replaceable high molecular mass linear polyacrylamide solution (high molecular mass LPA) was used to achieve long read-lengths for DNA sequencing by capillary electrophoresis (E. Carrilho et al., Anal. Chem. 1996, 68, 3305-3313). In that work, the polymer was prepared by polymerization in water at 6% w/w, followed by dilution to 2% w/w. In this study, an improved method for preparation of high molecular mass LPA was developed, based on inverse emulsion polymerization. With this polymerization procedure, the LPA results in a molecular mass of approximately 9 MDa, with characteristics of a fine powder of high purity and practically unlimited shelf life. Using size exclusion chromatography (SEC) and viscosity measurements to characterize the polymer, good batch-to-batch reproducibility was found. It was observed that the viscous polymer solutions made from these high molecular mass polymers require careful preparation and handling because the method of dissolution could affect the molecular mass distribution and the resultant separation of DNA components. Solutions containing 2% w/w of LPA made by emulsion polymerization were simple to prepare, resulting in excellent performance as a replaceable matrix for DNA sequencing by capillary electrophoresis. The viscosity of the polymer decreased exponentially when pressure was applied, allowing easy replacement from a capillary using a syringe. With a properly prepared matrix, a read-length of more than 1000 bases in 80 min with an accuracy better than 97%, and better than 99% for the first 800 bases, could be achieved.

Experimental determination of the effective point of measurement of a parallel-plate ionisation chamber.

The effective point of measurement (EPM) of a Kemp-Barber parallel plate ionisation chamber exposed to cobalt-60 has been determined experimentally. The variation of the EPM as a function of plate separation and the build-up cap thickness has also been studied. In general, for a constant size of build-up cap, the EPM moves downstream from the inner front wall towards the back wall of the chamber as the plate separation decreases. For parallel plate chambers, conventional theoretical analyses suggest that the EPM is the inner front wall and that it shifts towards the geometric centre of the chamber as the plate separation increases. The experimentally determined variation of the EPM, which appears to contradict these conclusions, suggests that the distribution of ionisation within a parallel plate chamber is not adequately accounted for in present theoretical descriptions. Such considerations may also affect other experimental determinations of the EPM for cylindrical chambers, as many are based on a comparison using parallel plate ionisation chambers with an assumed EPM on the inner front wall.

DNA sequencing: modular primers for automated walking.

Here we describe our progress in the development of the technology of DNA sequencing by primer walking based on the modular primer approach, which eliminates the primer synthesis bottleneck. Modular primers are assembled from 5-mers, 6-mers, or 7-mers selected from a presynthesized library of as few as 1000 oligonucleotides. This technology is expected to reduce the time per walk by a factor of 20 to 50, and the cost of DNA sequencing by a factor of 5 to 15. Both time and expense will be saved not only on the primer synthesis per se but, more importantly, as a result of the closed-end automation of the complete cycle of walking sequencing, where no human intervention will be required between the walks. Such closed-end automation has until now been precluded due to the need to synthesize a new primer for each walk. As a part of the closed cycle automation development, this report deals with modular primers used for sequencing with fluorescent dye terminators. The success rate and the quality of automated sequencing with modular primers are found similar to those with the conventional 17-20-base-long primers. One of the advantages of the described technique is simple purification without any proteins that need to be removed.

Case study of the effects of prolonged and severe anorexia nervosa on bone mineral density.

Among the most severe sequelae of anorexia nervosa (AN) are its skeletal complications. Young women who have AN during adolescence may not attain their expected peak skeletal mass, and may enter adulthood with reduced bone mineral density (BMD) and an increased risk of fracture. This case history describes a young woman with severe AN that included prolonged exposure to both low body weight and amenorrhea. BMD measurement during the acute stage of her illness revealed severe osteopenia. Six years after recovery from AN, follow-up studies demonstrated only modest gains in BMD, with measurements for the hip and lumbar spine that are greater than 2 SDs below the age-matched mean.

DNA sequencing: modular primers assembled from a library of hexamers or pentamers.

Here we report a striking effect displayed by "modular primers," which consist of hexamer or pentamer oligonucleotide modules base-stacked to each other upon annealing to a DNA template. Such a combination of modules is found to prime DNA sequencing reactions uniquely, unlike either of the modules alone. We attribute this effect in part to the increase in the affinity of an oligonucleotide for the template in the presence of an adjacent module. All possible pentamer (or hexamer) sequences total 1024 (or 4096) samples, a manageable size for a presynthesized library. This approach can replace the synthesis of primers, which is the current bottleneck in time and cost of the primer walking sequencing, and can allow full automation of the closed cycle of walking.

A nationwide survey of 222Rn and gamma radiation levels in Australian homes.

A nationwide survey of Australian homes was conducted to determine the average annual dose equivalents to the Australian population from exposure to Rn and gamma radiation. The exposure to Rn was measured using solid-state track detectors (SSTD), while the gamma radiation dose was concurrently determined using thermoluminescent dosimetry. Dosimeters were placed in approximately 3,400 randomly distributed homes (representing about 1 in 1,400 occupied dwellings) for 12 mo. The average Rn concentration in Australian homes measured over a year is 11 Bq m-3. Using appropriate conversion factors, the annual average effective dose equivalents to the Australian population were determined to be 0.5 mSv and 0.9 mSv for Rn and gamma radiation exposure, respectively.

Modeling human calcium tracer kinetics using a minimum of assumptions.

A conceptually simple model of human calcium kinetics, based on the Bauer-Carlsson-Linquist (B.C.L.) expression, is presented. The B.C.L. model assumes tracer retention in the body, occurs either in an exchangeable pool or in the skeleton, and the rate of calcium transfer from pool to bone (mineralization) is constant. As a modification, it is demonstrated that the existence of an expanding calcium pool and its rate of expansion may be directly determined from the raw data, without a priori assumptions. If data on whole body retention are unavailable, the concept of dermal tracer loss as the difference between tracer excretion and whole body retention may be used to estimate whole body retention. It has been possible to compare the modified B.C.L. expression with various multicompartmental kinetic models by analyzing raw data supplied by other workers and making comparisons with their published results. As methodologies are very different, the two sets of estimates of bone mineralization rate and exchangeable pool size have been ranked within individual groups. In five of six comparisons, the results indicate a rank correlation coefficient with a p-value better than 0.05 occurred. In all cases of data analysis from "normal" subjects, the calcium pool was found to be expanding. The existence of an expanding pool renders the model similar to a previous one, but the present one is conceptually and mathematically simpler in achieving equivalent results.