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Preparation of bone samples in the Gliwice Radiocarbon Laboratory for AMS radiocarbon dating.

In the Gliwice Radiocarbon Laboratory, a system for preparation of samples for AMS dating has been built. At first it was used to produce graphite targets from plant macrofossils and sediments. In this study we extended its capabilities with the preparation of bones. We dealt with 3 methods; the first was the classical Longin method of collagen extraction, the second one included additional treatment of powdered bone in alkali solution, while in the third one carboxyl carbon was separated from amino acids obtained after hydrolysis of protein. The suitability of the methods was tested on 2 bone samples. Most of our samples gave ages > 40 kyr BP, suggesting good performance of the adapted methods, except for one sample prepared with simple Longin method. For routine preparation of bones we chose the Longin method with additional alkali treatment.

Amino Acids↗

Effectiveness of multiple internal standards: deuterated analogues of methylenedioxymethamphetamine, methylenedioxyamphetamine, methamphetamine, and amphetamine.

With the increasing abuse of methylenedioxymethamphetamine (MDMA) thereby requiring analysis, we have undertaken a systematic evaluation on parameters associated with the analysis of MDMA and related compounds, including methylenedioxyamphetamine (MDA), methamphetamine (MA), and amphetamine (AM). Parameters studied included three solid-phase adsorbents, five derivatization reagents, and four deuterated internal standards (IS). This report examines whether differences in quantitation data derived from the use of four ISs (one for each analyte) and two ISs (one for AM and MA, one for MDA and MDMA) are statistically significant. Two types of samples were included in this study. The first type (Type I) included four replicate sets of standard solutions prepared in urine matrix. All analytes (AM, MA, MDA, and MDMA) were included in all samples, and these analytes' concentrations in each set were at five levels (100, 250, 500, 1000, and 2000 ng/mL). Four deuterated analogues (MA-d(8), AM-d(8), MDMA-d(5), and MDA-d(5)) at 500 ng/mL were also included in all solutions. The second type of samples (Type II) included 25 case urine specimens. Most of these specimens contained MA/AM and/or MDMA/MDA. The specific objective of this study is to determine whether the 4-IS approach can indeed generate better quantitative data than a less-costly 2-IS. For Type I samples, where the true concentrations of the analytes are known, two-sample t-test is adapted to examine whether the two sets of prediction errors (i.e., known concentration minus calculated concentration) resulting from the 4-IS and the 2-IS approaches are statistically different. For Type II samples, where the analytes' true concentrations are unknown, one-sample t-test was adapted to determine whether the difference of the quantitation results derived from the 4-IS and the 2-IS approaches is statistically significant. Statistical analysis of quantitation data derived from Types I and II samples indicates that differences in MDA and MDMA concentrations resulting from the use of one (MDA-d(5) or MDMA-d(5)) or two (MDA-d(5) and MDMA-d(5)) are statistically nonsignificant. On the other hand, similar analysis on data derived from Type I samples indicate the use of the analytes' respective deuterated analogues as the ISs appear to generate better quantitative data for AM and MA.

3,4-Methylenedioxyamphetamine↗

Analysis of the WAIS-III Index score scatter using the significant deviation from the mean of the four Index scores.

Despite their validity and their potential clinical interest, the WAIS-III Index scores seem less used by clinicians than the traditional IQs. One of reason of this lack of interest in the Indices is the relative complexity of their interpretation. We advocate the use of the average index score as a baseline to analyze the Index score variability and to identify strengths and weaknesses in the profile of the Index scores. Davis's formula provides reference values to be used to highlight the Index scores significantly moving away from the baseline. The usefulness of this method is illustrated with the analysis the Index score scatter in the standardization sample of the French adaptation of the WAIS-III. A rather important dispersion of the Index scores around the average index score was observed, a large percentage of standardization sample showing one or two Index scores significantly different from the baseline.

Adolescent↗

InJection adaptable fine ionization source ('JaFIS') for continuous flow nano-electrospray.

Nanoelectrospray ('nanoES') tandem mass spectrometry of complex peptide mixtures has become a certified, mostly reliable technique for the identification of proteins. The typical low flow rates of nanoES, the extended analysis times for small samples, high ion transmission and its overall ease-of-use provide important practical advantages for polypeptide covalent microanalysis. We have constructed a modified nanoES ion source that is highly durable and user-friendly, and potentially allows for full auto-sampling operation. The inJection adaptable Fine Ionization Source ('JaFIS') can be operated at flow rates of 10-100 nL per minute and with sensitivities in the 25 femtomoles peptide per microliter range. The ion spray needles usually last for days, allowing for standards and multiple samples to be analyzed consecutively under similar conditions. In this configuration, quality controlled needles can also be saved and reused, providing for more consistent and reproducible day-to-day operating conditions, JaFIS-ES also permits sample recovery should any failure occur during analysis.

Databases, Factual↗

[Body-related locus of control in healthy and chronically ill adolescents].

The present contribution analyses body-related locus of control beliefs in healthy and chronically ill adolescents. Moreover, we asked which bearing locus of control beliefs have on psychosocial adaptation. We examined a sample of asthmatic and diabetic adolescents and a sample of healthy adolescents aged 12 to 16 using the KLC-questionnaire. The questionnaire measures the locus of control concerning health, appearance and physical ability. Regarding the structure of body-related locus of control beliefs, the results show no differences between healthy and chronically ill adolescents; but the ill adolescents show less external locus of control. In the sample of chronically ill adolescents the locus of control is independent of severity and duration of their illness. Significant correlations between external locus of control and psychosocial adaptation could only be found in healthy adolescents. The results are discussed based on illness-specific experiences and general characteristics of adolescent body image.

Adaptation, Psychological↗

Data management in a two-dimensional gel electrophoresis laboratory: "gelscript 1" software.

We have developed a software package "gelscript 1", to perform data operations in a laboratory that runs and analyzes a large number of two-dimensional (2-D) gels. This system is managed automatically by the "4th Dimension" relational database on a Macintosh platform. A guiding principle in the development of "gelscript 1" was that any piece of information is entered into the system only once, and is retrieved, copied, inserted or checked whenever required. In addition to saving labor, this principle ensures consistency and integrity of the database. The system always "knows" how many gels were run from any one sample, how long the films were exposed or were supposed to be exposed. It keeps track of data throughout all operations, warns of improper sample assignments, and prints labels for films, samples, protocols, etc. The software can be adapted to other applications, in which many samples are processed and where cross-referencing is needed.

Databases, Factual↗

Tomographic imaging with nonuniform angular sampling.

A new class of polar sampling patterns for projection imaging is described. In contrast to conventional techniques, a nonuniform variation of the angular increments between consecutive projections is introduced. The proposed method allows adaptation of the polar sampling pattern to different shapes of the object. Numerical simulations and MR experiments verify that angular sampling density can be varied according to the radial extension of the object, resulting in a reduction of the total number of required projections (and X-ray exposure) compared with conventional circular field-of-view imaging.

Technology, Radiologic↗

Dim light adaptation attenuates acute melatonin suppression in humans.

Abstract Studies in rodents with retinal degeneration indicated that neither the rod nor the cone photoreceptors obligatorily participate in circadian responses to light, including melatonin suppression and photoperiodic response. Yet there is a residual phase-shifting response in melanopsin knockout mice, which suggests an alternate or redundant means for light input to the SCN of the hypothalamus. The findings of Aggelopoulos and Meissl suggest a complex, dynamic interrelationship between the classic visual photoreceptors and SCN cell sensitivity to light stimuli, relative to various adaptive lighting conditions. These studies raised the possibility that the phototransductive physiology of the retinohypothalamic tract in humans might be modulated by the visual rod and cone photoreceptors. The aim of the following two-part study was to test the hypothesis that dim light adaptation will dampen the subsequent suppression of melatonin by monochromatic light in healthy human subjects. Each experiment included 5 female and 3 male human subjects between the ages of 18 and 30 years, with normal color vision. Dim white light and darkness adaptation exposures occurred between midnight and 0200 h, and a full-field 460-nm light exposure subsequently occurred between 0200 and 0330-h for each adaptation condition, at 2 different intensities. Plasma samples were drawn following the 2-h adaptation, as well as after the 460-nm monochromatic light exposure, and melatonin was measured by radioimmunoassay. Comparison of melatonin suppression responses to monochromatic light in both studies revealed a loss of significant suppression after dim white light adaptation compared with dark adaptation (p < 0.04 and p < 0.01). These findings indicate that the activity of the novel circadian photoreceptive system in humans is subject to subthreshold modulation of its sensitivity to subsequent monochromatic light exposure, varying with the conditions of light adaptation prior to exposure.

Adaptation, Ocular↗

The adaptation of existing personal inhalable aerosol samplers for bioaerosol sampling.

Health-related monitoring of bioaerosol exposures in the workplace should ideally be carried out using size-selective personal samplers that separate the aerosol into biologically relevant size fractions and allow both quantification and identification of the microorganisms present in each fraction. As a first stage in the development of personal bioaerosol samplers a number of collection substrates were assessed for their ability to maintain the viability of the collected microorganisms, so that subsequent culturing and species identification may be carried out. The substrates were tested with bioaerosols of varying robustness, consisting of Saccharomyces cerevisiae cells, Escherichia coli cells, and Penicillium expansum spores, aerosolized under controlled environmental conditions. The survival of microorganisms on each test substrate, assessed on the basis of the culturable fractions of cells recovered, was compared with that of microorganisms collected in a reference glass cyclone sampler. These bioefficiency tests identified the substrate combinations with the potential to fulfill personal sampler design criteria. The substrates were then subjected to further development to evaluate and optimize their particle size selection characteristics. The outcome of this work is two prototype personal bioaerosol samplers in which size-selective substrates are adapted for use in existing designs of personal inhalable sampler. This offers an effective and low-cost solution to personal monitoring of bioaerosol exposures in the workplace.

Aerosols↗

The development and validation of a behavior rating scale for blood sampling with children.

This article describes the development of a behavior rating scale, which was designed to measure children's behaviors during a blood sampling procedure. Trained observers were able to reliably use the behavior rating scale while observing children's behaviors during blood sampling in a pediatric hospital. Evidence of the instrument's validity was found in a treatment study. In that experiment, youngsters were prepared for the blood sampling procedures by viewing films. Those watching coping or mastery models before blood sampling evidenced significantly higher adaptive responses on the behavior rating scale than those who watched a control film. The behavior rating scale was also significantly related to a global rating and a self-report measure, but not to a physiologic index of anxiety. In summary, the constructed behavior rating scale appears to be a reliable and valid instrument for assessing children's behavior during blood sampling procedures.

Adaptation, Psychological↗

Measurement of halofantrine and its major metabolite desbutylhalofantrine in plasma and blood by high-performance liquid chromatography: a new methodology.

A new high-performance liquid chromatographic assay for the measurement of halofantrine and desbutylhalofantrine in plasma and whole blood is described. The method involves a smaller sample volume, simplified sample pre-treatment and a shorter run-time, and is adaptable to the measurement of samples dried onto filter paper strips. Using this method, which is both selective and sensitive, plasma concentration versus time profiles for both substances have been investigated following a single oral dose (500 mg) of halofantrine hydrochloride to a healthy adult volunteer. In addition, a clinical study designed to evaluate the disposition and elimination of the two compounds in children with non-severe falciparum malaria is in progress.

Antimalarials↗

Depression and health in family caregivers: adaptation over time.

This study examined the predictors of caregiver depression and "adaptation" over time in a sample of 202 family caregivers of cognitively impaired adults. By examining caregiver adaptation (i.e., a caregiver's ability to adjust psychologically to the demands of providing long-term in-home care), we were able to account for initial levels of depression, regression to the mean, and floor and ceiling effects. Results indicated that the strongest predictors of caregiver depression 1 year after baseline were initial levels of depression, worsening of caregiver subjective physical health status and burden, and short-term use of in-home respite assistance. These findings suggest that caregivers who experience deterioration in levels of physical health and burden and who use in-home respite on a short-term or sporadic basis may be especially vulnerable to the chronic stress of providing long-term in-home care.

California↗

Adaptation of aquatic microbial communities to hg stress.

The mechanism of adaptation to Hg in four aquatic habitats was studied by correlating microbially mediated Hg volatilization with the adaptive state of the exposed communities. Community diversity, heterotrophic activity, and Hg resistance measurements indicated that adaptation of all four communities was stimulated by preexposure to Hg. In saline water communities, adaptation was associated with rapid volatilization after an initial lag period. This mechanism, however, did not promote adaptation in a freshwater sample, in which Hg was volatilized slowly, regardless of the resistance level of the microbial community. Distribution of the mer operon among representative colonies of the communities was not related to adaptation to Hg. Thus, although volatilization enabled some microbial communities to sustain their functions in Hg-stressed environments, it was not mediated by the genes that serve as a model system in molecular studies of bacterial resistance to mercurials.

Journal Article↗

[Clinical trials in dermatology. Statistical support].

To determine the efficacy or safety of new topical treatments, more or less standardized studies must be performed. This article presents several examples of statistical analyses of the data currently seen in the dermatology area, and some guidelines for study sample size determination. More importantly, it indicates, for as soon as phase I studies, the need for preliminary informations such as development strategy, historical data, literature references or pilot studies, to determine or adapt appropriate designs and sample sizes. This need can be filled by close collaboration among clinicians, statisticians and sponsor.

Clinical Trials as Topic↗

Bayesian population model of methotrexate to guide dosage adjustments for folate rescue in patients with breast cancer.

BACKGROUND: Methotrexate (MTX) infusions may induce severe side-effects, and alkaline hydration along with folinic acid rescue is a common way to reduce such toxic risks. The purpose of this study was to develop an adaptive rescue strategy based upon the early detection of patients with impaired MTX elimination. METHODS AND RESULTS: In this study, we propose a simple population-based Bayesian approach for predicting MTX plasma concentration from a limited number of samples, so as to adapt both duration and dosage of the rescue agent to be used next. Ten kinetic profiles obtained after 10 courses of MTX (1.5 g/m2) in seven patients with inflammatory breast cancer were used to establish the population pharmacokinetic parameters (Cl, 8.16 L/h; t1/2, 12.7 h). This population was next involved in the Bayesian estimation of MTX individual pharmacokinetic parameters from only two blood samples (T24 and T36 h), thus allowing one to forecast the elimination of this drug by predicting MTX levels at 48 h. According to the MTX concentrations predicted during the elimination phase, folinic acid rescue was then prolonged in patients likely to be overexposed. CONCLUSION: The Bayesian estimation presented in this study was an easy and convenient method to efficiently detect patients with impaired MTX elimination in routine clinical practice. This information enabled the introduction of strategies for minimizing the risk of severe drug toxicity.

Adult↗

Group-selective determination of total N-nitroso compounds in nitrate-containing human urine samples.

A group-selective method for the determination of total N-nitroso compounds (NOC) has been adapted for analysing human urine samples. Nitrate was first removed from urine by an anion-exchange procedure that prevented the significant loss of various added reference NOC and unidentified urinary NOC. The total NOC were then determined by injecting the urine sample (nitrate content less than 1 mmol l-1) or anion-exchange eluate into refluxing ethyl acetate containing either acetic acid for determining heat and acetic acid labile thermal energy analyser responsive compounds (TAC) or into hydrogen bromide for the determination of TAC and NOC. The nitrogen monoxide levels released were measured using thermal energy analysis with chemiluminescence detection, and the differnce between the two determinations represented the concentrations of NOC. The optimum conditions for preventing artefactual nitrosation in urine samples by the addition of sodium hydroxide or sulphamic acid without decomposition of NOC were determined. The influence of time and storage conditions on NOC stability was investigated. Fifteen urine samples collected from volunteers dosed with proline were analysed for total NOC and N-nitrosamino acids revealing a preponderance of unknown NOC. The determination of total NOC in human urine using this group-selective method offers a new approach to the estimation of human exposure to NOC and to isolate hitherto unknown NOC and their metabolites.

Chromatography, Gas↗

Enzyme immunoassay of 17 beta-estradiol, estrone conjugates, and testosterone in urinary and fecal samples from male and female mice.

ELISA measures of 17 beta-estradiol, estrone conjugates, and testosterone were adapted for fecal and urinary samples from laboratory mice. We will report on validations of these assays and data from interacting males and females. Unconjugated gonadal steroids were consistently measurable in urine and feces of both males and females. Females that were parturient following insemination excreted relatively low levels of urinary testosterone compared to non-parturient females. The results are consistent with evidence that elevated androgens and estrogens are incompatible with intrauterine implantation of fertilized ova, and suggest that steroids in male urine could contribute to pheromonal action. These methods permit repeated noninvasive measurement of steroid activity in this species.

Animals↗