Performance comparison of two Olympus InnovX handheld x-ray analyzers for feasibility of measuring arsenic in skin in vivo - Alpha and Delta models.

The Figure-Of-Merit (FOM) performance, a combination of detection limit and dose, is compared between two generations of handheld X-Ray Fluorescence (XRF) spectrometers for the feasibility of in vivo XRF measurement of arsenic (As) in skin. The Olympus InnovX Delta model analyzer (40 kVp using either 37 or 17µA) was found to show improvements in Minimum Detection Limit (MDL) using arsenic As-doped skin calibration phantoms with bulk tissue backing, when compared to the first generation InnovX Alpha model (40kVp, 20µA) in 120s measurements. Differences between two different definitions of MDL are discussed. On the Delta system, an MDL of (0.462±0.002) µg/g As was found in phantoms, with a nylon backing behind to mimic bulk tissue behind skin. The equivalent and effective doses were found to be (10±2) mSv and ~7×10-3µSv respectively for the Alpha and (15±4) mSv and ~8×10-3µSv respectively for the Delta system in 120s exposures. Combining MDL and effective dose, a lower (better) FOM was found for the Delta, (1.7±0.4) ppm mSv1/2, compared to (4.4±0.5) ppm mSv1/2 for the Alpha model system. The Delta analyzer demonstrates improved overall system performance for a rapid 2-min measurement in As skin phantoms, such that it can be considered for use in populations exposed to arsenic.

Age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto.

OBJECTIVE: To study the age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto. APPROACH: A 109Cd K x-ray fluorescence (KXRF) measurement system was used from 2009 to 2011 in a study that measured the bone lead (Pb) concentration of 263 environmentally exposed individuals residing in Toronto, Ontario, Canada. Tibia (cortical bone) and calcaneus (trabecular bone) lead contents were measured in 134 males and 129 females between 1 and 82 years of age. Whole blood Pb concentration was measured by TIMS (thermal ionization mass spectrometer). Tibia (Ti) and calcaneus (Cal) Pb were examined versus the age of participants, taking into account uncertainties in bone Pb measurement values. MAIN RESULTS: No significant sex differences were observed in any of the age categories. Participants older than 50 years of age demonstrated the highest concentrations of Pb in their blood, tibia, and calcaneus bones. SIGNIFICANCE: In most of the previous publications, uncertainty was not considered in the regression model of bone Pb and age. However, in this paper, we adjusted the bone Pb values for the uncertainty level. This had a significant influence in regression models of bone Pb and thus we recommend that uncertainty be considered in future studies.

Impact of Insect Management on Population Dynamics and Insecticide Resistance of Tarnished Plant Bug (Hemiptera: Miridae).

While transgenic plants targeting lepidopteran and coleopteran insects have been available for almost 20 yr, there are no transgenic crops that target hemipteran insects such as tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), though at least one company lists potential products in advanced stages of development. A resistance management model for the U.S. Mid-South was developed to aid in resistance risk assessments for transgenic crops targeting L. lineolaris, and validated against the prior case of pyrethroid resistance in this insect. The model predicted that resistance to a pyrethroid would evolve in 17.6-21.0 yr (depending on the initial resistance allele frequency), which was close to the 15-20 years observed in the field. Due to uncertainty in female fecundity, we varied fecundity from 3 eggs/female/day to 12 eggs/female/day. Sprays were applied based on action thresholds, and increasing fecundity therefore increased the number of sprays applied per year and decreased durability. We also varied the action threshold in cotton (Gossypium hirsutum L.) fields (the population levels at which sprays were applied) from 17,600/ha to as low as 1,100/ha. Lowering the threshold increased the number of sprays applied, but also increased durability of the pesticide. Removing the noncotton host refuge present at the same time as cotton changed the relationship so that increasing the action threshold increased durability. The impact of insect resistance management on action threshold cost estimates will vary depending on the landscape, and cannot be assumed to always move the economic injury level in the same direction.

Feasibility of measuring arsenic and selenium in human skin using in vivo x-ray fluorescence (XRF)--a comparison of methods.

In recent years, in vivo measurement systems of arsenic in skin by K-shell x-ray fluorescence (XRF) have been developed, including one which was applied in a pilot study of human subjects. Improved tube-based approaches suggest the method can be further exploited for in vivo studies. Recently, it has been suggested that selenium deficiency is correlated with arsenic toxicity. A non-invasive measurement of both elements could therefore be of potential interest. The main aim of this current study was to evaluate and compare the performance of an upgraded portable XRF system and an advanced version of the benchtop XRF system for both selenium and arsenic. This evaluation was performed in terms of arsenic and selenium Kα detection limits for a 4W gold anode Olympus InnovX Delta portable analyzer (40 kVp) in polyester resin skin-mimicking phantoms. Unlike the polychromatic source earlier reported in the literature, the benchtop tube-based technique involves monochromatic excitation (25 W silver anode, manufactured by x-ray optics, XOS) and a higher throughput detector type. Use of a single exciting energy allows for a lower in vivo dose delivered and superior signal-noise ratio. For the portable XRF method, arsenic and selenium minimum detection limits (MDLs) of 0.59 ± 0.03 ppm and 0.75 ± 0.02 ppm respectively were found for 1 min measurement times. The MDLs for arsenic and selenium using the benchtop system were found to be 0.35 ± 0.01 ppm and 0.670 ± 0.004 ppm respectively for 30 min measurement times. In terms of a figure of merit (FOM), allowing for dose as well as MDL, the benchtop system was found to be superior for arsenic and the two systems were equivalent, within error, for selenium. We shall discuss the performance and possible improvements of each system, their ease of use and potential for field application.

Comparisons of Lygus lineolaris (Hemiptera: Miridae) Populations from Two Distinct Geographical Regions of Mississippi.

The tarnished plant bug, Lygus lineolaris (Palisot de Beauvois) (Hemiptera: Miridae), is a major pest of cotton (Gossypium hirsutum L.) in the state of Mississippi. Economic data indicate that L. lineolaris is a more serious pest of cotton in the Delta region of Mississippi than in the Hills region; however, little data exist comparing the two populations. Two experiments were undertaken to compare L. lineolaris from these two geographically distinct regions. In the first experiment, colonies of L. lineolaris from each region were reared in the laboratory under controlled conditions and measurements of development time, survivorship, fecundity, and hatch rate were compared. The geographic region of origin had no effect on any of the variables measured; however, the diet used for rearing had a significant effect on all variables except hatch rate. In the second experiment, part of the cox1 gene of the L. lineolaris mitochondrial genome was compared between the two populations to examine possible genetic differences between L. lineolaris from the two regions of Mississippi. Data revealed two cox1 clades in the Delta region and only one cox1 clade in the Hills region. Taken together, the data do not explain the reason for the differences in the severity of damage to cotton in the two regions.

Uncertainty calculations for the measurement of in vivo bone lead by x-ray fluorescence.

In order to quantify the bone lead concentration from an in vivo x-ray fluorescence measurement, typically two estimates of the lead concentration are determined by comparing the normalized x-ray peak amplitudes from the Kalpha(1) and Kbeta(1) features to those of the calibration phantoms. In each case, the normalization consists of taking the ratio of the x-ray peak amplitude to the amplitude of the coherently scattered photon peak in the spectrum. These two Pb concentration estimates are then used to determine the weighted mean lead concentration of that sample. In calculating the uncertainties of these measurements, it is important to include any covariance terms where appropriate. When determining the uncertainty of the lead concentrations from each x-ray peak, the standard approach does not include covariance between the x-ray peaks and the coherently scattered feature. These spectral features originate from two distinct physical processes, and therefore no covariance between these features can exist. Through experimental and simulated data, we confirm that there is no observed covariance between the detected Pb x-ray peaks and the coherently scattered photon signal, as expected. This is in direct contrast to recent work published by Brito (2006 Phys. Med. Biol. 51 6125-39). There is, however, covariance introduced in the calculation of the weighted mean lead concentration due to the common coherent normalization. This must be accounted for in calculating the uncertainty of the weighted mean lead concentration, as is currently the case. We propose here an alternative approach to calculating the weighted mean lead concentration in such a way as to eliminate the covariance introduced by the common coherent normalization. It should be emphasized that this alternative approach will only apply in situations in which the calibration line intercept is not included in the calculation of the Pb concentration from the spectral data: when the source of the intercept is well characterized and known to come from trace contamination by Pb in the plaster of Paris calibration standards. In our approach, the coherent normalization is only applied to one parameter and we no longer take a weighted mean of correlated quantities. Our proposed alternative calculation has essentially no effect on the calculated error of the mean lead concentration, indicating that the existing method of accounting for this covariance is sufficient.

Calibration and characterization of a digital X-ray fluorescence bone lead system.

Five different combinations of digital shaping parameters were tested for a newly assembled. 109Cd source, K X-ray fluorescence bone lead system. System calibration results are presented, along with analyses of measurement uncertainty and reproducibility obtained from repeat measurements of a bone phantom and a human tibia. Digital shaping parameters of 2.4 micros for a rise time/fall time and 1.2 micros for a flat top width were identified as superior. The digital system provided significant improvements in overall measurement precision, with gains of at least 25-35% over conventional system results.

A comparative study of the adsorption of amino acids on to calcium minerals found in renal calculi.

To assess the binding of individual amino acids to the principal calcium minerals found in human kidney stones, the adsorption of 20 amino acids on to calcium oxalate monohydrate, CaHPO4*2H2O, Ca3(PO4)2 and Ca5(PO4)3OH crystals was determined over the physiological urinary pH range (pH 5-8) in aqueous solutions. All amino acids adsorbed most strongly at pH 5, and this decreased in all cases as the pH was increased. The amino acids which adsorbed most strongly were aspartic acid, glutamic acid and gamma-carboxyglutamic acid, with the last displaying the strongest affinity. All amino acids bound more avidly to calcium oxalate monohydrate than to any of the phosphate minerals. Adsorption on to CaHPO4*2H2O was generally higher than for Ca3(PO4)2 and Ca5(PO4)3OH, for which all amino acids, with the exception of gamma-carboxyglutamic acid, had only a weak affinity. The binding affinity of these acids is thought to be due to their zwitterions being able to adopt conformations in which two carboxyl groups, and possibly the amino group, can interact with the mineral surface without further rotation. The strong binding affinity of di-and tri-carboxylic acids for calcium stone minerals indicates that proteins rich in these amino acids are more likely to play a functional role in stone pathogenesis than those possessing only a few such residues. These findings, as well as the preferential adsorption of the amino acids for calcium oxalate monohydrate rather than calcium phosphate minerals, have ramifications for research aimed at discovering the true role of proteins in stone formation and for potential application in the design of synthetic peptides for use in stone therapy.

Intracrystalline proteins and the hidden ultrastructure of calcium oxalate urinary crystals: implications for kidney stone formation.

The external appearance of urinary calcium oxalate (CaOx) crystals suggests that they are solid, homogeneous structures, despite their known association with proteins. Our aim was to determine whether proteins comprising the organic matrix of CaOx crystals are superficial or intracrystalline in order to clarify the role of urinary proteins in the formation of kidney stones. CaOx crystals were precipitated from centrifuged and filtered, or ultrafiltered, healthy human urine. They were then treated with dilute NaOH to remove bound proteins, partially demineralized with EDTA, or fractured and subjected to limited proteolysis before examination by low-resolution scanning electron microscopy or field emission scanning electron microscopy. Crystals precipitated from centrifuged and filtered urine had a complex interior network of protein distributed throughout the mineral phase, which appeared to comprise closely packed subcrystalline particles stacked in an orderly array among an amorphous organic matrix. This ultrastructure was not evident in crystals deposited in the absence of macromolecules, which were completely solid. This is the first direct evidence that crystals generated from cell-free systems contain significant amounts of protein distributed throughout a complex internal cribriform ultrastructure. Combined with mineral erosion in the acidic lysosomal environment, proteins inside CaOx crystals would render them susceptible to attack by urinary and intracellular renal proteases and facilitate their further dissolution or disruption into small particles and ions for removal by exocytosis. The findings also have broader ramifications for industry and the materials sciences, as well as the development and resorption of crystals in biomineralization systems throughout nature.

Sexual dimorphism and aromatase in the rat retina.

The present study: (a) determined the effects of both pre- and early postnatal androgen hormonal manipulation on retinal thickness, (b) examined the presence of the aromatase enzyme by immunocytochemistry in retinal tissue and (c) quantified aromatase activity in the rat retina. The results suggest that retinal thickness is influenced by perinatal hormone manipulation via aromatizable androgens that have implications for the sex differences seen in visual information processing and performance.

Pre- or postnatal testosterone and flutamide effects on sexually dimorphic nuclei of the rat hypothalamus.

Utilizing the sexually dimorphic nature of hypothalamic nuclei, a determination of the effects of pre- or postnatal flutamide and testosterone treatments were examined in male and female rats. Statistical analysis compared treatments, sex, and time of injection in terms of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anteroventral periventricular nucleus (AVPV) volumes and lengths. The present findings establish that pre- or postnatal hormonal environments are crucial in influencing sexual morphology on the developing brain.

The hole truth: intracrystalline proteins and calcium oxalate kidney stones.

The ultimate aim of our research is to understand the role of macromolecules in the formation of human kidney stones, particularly their interactions with calcium oxalate (CaOx) crystals. The invariable association of stones with proteins raises the possibility that proteins play a role in their formation, similar to the role of proteins in healthy biomineralization. Do these proteins induce mineralization? Are they merely a response to the disease process? Or are they protective molecules that were overwhelmed by mineral supersaturation? A protein of particular interest is fragment 1 (F1) of prothrombin. We have shown that mRNA for prothrombin is present in the kidney. Because the F1 fragment of prothrombin present in urine is slightly different from that found in the blood, we refer to this protein as "urinary prothrombin fragment 1" (UPTF1). Available evidence suggests that the kidney manufactures the protein for protection against stone disease and that the protein has a directive role in stone formation. We now have evidence that proteins are interred within CaOx crystals precipitated from human urine, where it is distributed in continuous channels. These proteins could facilitate crystal deconstruction and removal after attachment to the renal epithelium and endocytosis. We suspect that the formation of CaOx crystals in the urine is a normal process designed to permit harmless disposal of an excess of calcium, oxalate, or both. The incorporation of proteins provides a second line of defense against stone formation by enabling the destruction and removal of retained crystals. Understanding the basic molecular strategies by which plants produce protein-containing CaOx crystals may provide insight into human CaOx stone formation.

Relationship between sexual behavior and sexually dimorphic structures in the anterior hypothalamus in control and prenatally stressed male rats.

The present study was designed to examine the effects of prenatal stress on the morphological development of sexually dimorphic structures in the anterior hypothalamus in male rats and to determine if there is a relationship between morphologic development of the brain and copulatory behavior in individual animals. Dams in the stress group were subjected to treatments of heat-light restraint during the third trimester of gestation (day 14 to parturition) three times daily for 45-min periods. At 90 days of age, prenatally stressed and control male offspring were tested during the dark cycle for spontaneous male sexual behavior. Volumes of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anteroventral periventricular nucleus (AVPV) were measured. Comparisons were made between copulatory behavior and hypothalamic nuclear volumes. SDN-POA volumes were significantly reduced (feminized; males have a larger SDN-POA than females) in prenatally stressed males that did not copulate, whereas, SDN-POA volumes in prenatally stressed males that copulated were not altered. The few control males that did not copulate (sexually non-active) also had significantly reduced SDN-POA volumes compared to the control males that did copulate (sexually active). The volume of the AVPV was significantly increased (feminized; males have a smaller AVPV than females) in prenatally stressed males that were sexually non-active compared to AVPV volumes in sexually active males. The results obtained in this study provide a strong positive relationship between sexual behavior and the morphology of the two sexually dimorphic structures measured.

The O'Flaherty model of lead kinetics: an evaluation using data from a lead smelter population.

The O'Flaherty model of lead kinetics is a physiologically based computer model of lead disposition in humans. The model is based on an age-dependent approach to human growth, with particular attention devoted to bone metabolism. As such, model output is well suited for comparison with noninvasive bone lead measurements made via X-ray fluorescence. A subset of workers from a lead smelter population were selected for an initial evaluation of the O'Flaherty model. Detailed blood lead records were used to define input. Simulated bone lead and blood lead output were compared with observation, enabling a refinement of model parameters. A revised version of the O'Flaherty model was then evaluated for the smelter population as a whole. Previously observed trends for the accumulation of lead in cortical bone and the release of lead from bone stores were well explained by the revised model. Model predictions for the accumulation of lead in trabecular bone were not in accord with observed levels in the calcaneus. Model results from the smelter population are consistent with the hypothesis that a polymorphism in the delta-aminolevulinate dehydratase enzyme modifies the kinetics of lead in humans. Further refinements are suggested, which may enhance the ability of the model to explain the underlying relationships between lead exposure and the distribution of lead in the body.

Effects of pattern, spatial frequency, number, and rate of stimulus presentation on the accuracy of detection.

Brief trains of pulsed stimuli were used to assess whether magnocellular or parvocellular visual pathways could be differentiated perceptually. Trains of either one to four sine-wave, square-wave, or checkerboard gratings were presented at three temporal and two spatial frequencies to six observers. The task of the observer was to report the perceived number of stimuli (gratings) in a train. The difference between actual number and perceived number of gratings was recorded as an error score. It was found that neither the pattern nor the spatial frequency of the gratings significantly affected perceptual accuracy. On the other hand, the number of gratings in a train and the interstimulus interval between gratings produced significant differences. Perceptual accuracy was greater when lower numbers of gratings in a train were presented with longer interstimulus intervals. The observers typically reported fewer stimuli than were presented. The source of the discrepancy is discussed in terms of a light adaptive process initiated in the retina.

Effect of the delta-aminolevulinate dehydratase polymorphism on the accumulation of lead in bone and blood in lead smelter workers.

Lead inhibition of the zinc metalloenzyme delta-aminolevulinate dehydratase (ALAD) is one of the most sensitive indicators of blood lead levels. ALAD is polymorphic, with about 20% of Caucasians expressing the rarer ALAD2 allele. Previous studies indicated that this polymorphism may be a genetic factor in lead transport, metabolism, and/or distribution. Whole blood lead, serum lead, and ALAD genotype were determined for 381 lead smelter workers, including 70 workers expressing the ALAD2 allele, whose blood lead elevations were observed for more than 20 years of employment. The same employees demonstrated higher serum lead levels. Using a cumulative blood lead index (CBLI) for each worker, based on individual blood lead histories, and in vivo X-ray fluorescence measurements of bone lead to estimate total lead body burden, the slopes of linear relations of bone lead to CBLI were greater for workers homoallelic for ALAD1, indicating more efficient uptake of lead from blood into bone. This effect was most significant in calcaneus bone and for workers hired since 1977 [ALAD1-1: 0.0528 +/- 0.0028 and ALAD1-2 or 2-2: 0.0355 +/- 0.0031 (P < 0.001)]. Decreased transfer of blood lead into bone in individuals expressing the ALAD2 allele contrasted with increased blood lead. Thus the ALAD genotype affected lead metabolism and potentially modified lead delivery to target organs including the brain; however, the ALAD genotype did not significantly affect the net accumulation of lead in bone.

Effects of sexual behavioral manipulation on brain plasticity in adult rats.

The purpose of the present study was to determine the effects of sexual behaviorial manipulation on brain plasticity in adult male rats. Adult male Sprague-Dawley rats that copulated during male sexual behavior testing were divided into four groups: control male; gonadectomized (Gdx) male; sexually active male; and sexually nonactive male. Female animals were used as an additional control group. At the end of a 12-week experimental period, the animals were again tested for male sexual behavior and tested for sexual motivation. Sexual behavior manipulations over the 12-week period resulted in significant differences in mount latency, mount frequency, intromission latency, intromission frequency, ejaculation latency, and the postejaculation interval. In the motivation test, significant differences in the number of approaches, contacts, and crossings of an electrified grid separating the test animal from a receptive female were also observed. Sexually dimorphic nucleus of the preoptic area (SDN-POA) volumes in sexually nonactive males were significantly smaller than in control males or sexually active males. Anteroventral periventricular nucleus (AVPV) volumes in the male groups were not significantly altered by sexual behavioral manipulations, however, the nonactive AVPV vol. was the only vol. not significantly different from the control female vol. These data demonstrate that in the adult rat, sexual behavioral manipulations resulted in significant alterations in behavior and in the vol. of the SDN-POA and that the effect of sexual behavior on the AVPV needs to be further investigated.