Urinary naphthalene and phenanthrene as biomarkers of occupational exposure to polycyclic aromatic hydrocarbons.

OBJECTIVES: The study investigated the utility of unmetabolised naphthalene (Nap) and phenanthrene (Phe) in urine as surrogates for exposures to mixtures of polycyclic aromatic hydrocarbons (PAHs). METHODS: The report included workers exposed to diesel exhausts (low PAH exposure level, n = 39) as well as those exposed to emissions from asphalt (medium PAH exposure level, n = 26) and coke ovens (high PAH exposure level, n = 28). Levels of Nap and Phe were measured in urine from each subject using head space-solid phase microextraction and gas chromatography-mass spectrometry. Published levels of airborne Nap, Phe and other PAHs in the coke-producing and aluminium industries were also investigated. RESULTS: In post-shift urine, the highest estimated geometric mean concentrations of Nap and Phe were observed in coke-oven workers (Nap: 2490 ng/l; Phe: 975 ng/l), followed by asphalt workers (Nap: 71.5 ng/l; Phe: 54.3 ng/l), and by diesel-exposed workers (Nap: 17.7 ng/l; Phe: 3.60 ng/l). After subtracting logged background levels of Nap and Phe from the logged post-shift levels of these PAHs in urine, the resulting values (referred to as ln(adjNap) and ln(adjPhe), respectively) were significantly correlated in each group of workers (0.71 < or = Pearson r < or = 0.89), suggesting a common exposure source in each case. Surprisingly, multiple linear regression analysis of ln(adjNap) on ln(adjPhe) showed no significant effect of the source of exposure (coke ovens, asphalt and diesel exhaust) and further suggested that the ratio of urinary Nap/Phe (in natural scale) decreased with increasing exposure levels. These results were corroborated with published data for airborne Nap and Phe in the coke-producing and aluminium industries. The published air measurements also indicated that Nap and Phe levels were proportional to the levels of all combined PAHs in those industries. CONCLUSION: Levels of Nap and Phe in urine reflect airborne exposures to these compounds and are promising surrogates for occupational exposures to PAH mixtures.

Genome-wide association with bone mass and geometry in the Framingham Heart Study

BACKGROUND:Osteoporosis is characterized by low bone mass and compromised bone structure, heritable traits that contribute to fracture risk. There have been no genome-wide association and linkage studies for these traits using high-density genotyping platforms.METHODS:We used the Affymetrix 100K SNP GeneChip marker set in the Framingham Heart Study (FHS) to examine genetic associations with ten primary quantitative traits: bone mineral density (BMD), calcaneal ultrasound, and geometric indices of the hip. To test associations with multivariable-adjusted residual trait values, we used additive generalized estimating equation (GEE) and family-based association tests (FBAT) models within each sex as well as sexes combined. We evaluated 70,987 autosomal SNPs with genotypic call rates [greater than or equal to]80%, HWE p [greater than or equal to] 0.001, and MAF [greater than or equal to]10% in up to 1141 phenotyped individuals (495 men and 646 women, mean age 62.5 yrs). Variance component linkage analysis was performed using 11,200 markers.RESULTS:Heritability estimates for all bone phenotypes were 30-66%. LOD scores [greater than or equal to]3.0 were found on chromosomes 15 (1.5 LOD confidence interval: 51,336,679-58,934,236 bp) and 22 (35,890,398-48,603,847 bp) for femoral shaft section modulus. The ten primary phenotypes had 12 associations with 100K SNPs in GEE models at p < 0.000001 and 2 associations in FBAT models at p < 0.000001. The 25 most significant p-values for GEE and FBAT were all less than 3.5 x 10-6 and 2.5 x 10-5, respectively. Of the 40 top SNPs with the greatest numbers of significantly associated BMD traits (including femoral neck, trochanter, and lumbar spine), one half to two-thirds were in or near genes that have not previously been studied for osteoporosis. Notably, pleiotropic associations between BMD and bone geometric traits were uncommon. Evidence for association (FBAT or GEE p < 0.05) was observed for several SNPs in candidate genes for osteoporosis, such as rs1801133 in MTHFR; rs1884052 and rs3778099 in ESR1; rs4988300 in LRP5; rs2189480 in VDR; rs2075555 in COLIA1; rs10519297 and rs2008691 in CYP19, as well as SNPs in PPARG (rs10510418 and rs2938392) and ANKH (rs2454873 and rs379016). All GEE, FBAT and linkage results are provided as an open-access results resource at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.

Geometric Generalizations of the Power of Two Choices

A well-known paradigm for load balancing in distributed systems is the``power of two choices,''whereby an item is stored at the less loaded of two (or more) random alternative servers. We investigate the power of two choices in natural settings for distributed computing where items and servers reside in a geometric space and each item is associated with the server that is its nearest neighbor. This is in fact the backdrop for distributed hash tables such as Chord, where the geometric space is determined by clockwise distance on a one-dimensional ring. Theoretically, we consider the following load balancing problem. Suppose that servers are initially hashed uniformly at random to points in the space. Sequentially, each item then considers d candidate insertion points also chosen uniformly at random from the space,and selects the insertion point whose associated server has the least load. For the one-dimensional ring, and for Euclidean distance on the two-dimensional torus, we demonstrate that when n data items are hashed to n servers,the maximum load at any server is log log n / log d + O(1) with high probability. While our results match the well-known bounds in the standard setting in which each server is selected equiprobably, our applications do not have this feature, since the sizes of the nearest-neighbor regions around servers are non-uniform. Therefore, the novelty in our methods lies in developing appropriate tail bounds on the distribution of nearest-neighbor region sizes and in adapting previous arguments to this more general setting. In addition, we provide simulation results demonstrating the load balance that results as the system size scales into the millions.

A Geometric Approach to Slot Alignment in Wireless Sensor Networks

Traditionally, slotted communication protocols have employed guard times to delineate and align slots. These guard times may expand the slot duration significantly, especially when clocks are allowed to drift for longer time to reduce clock synchronization overhead. Recently, a new class of lightweight protocols for statistical estimation in wireless sensor networks have been proposed. This new class requires very short transmission durations (jam signals), thus the traditional approach of using guard times would impose significant overhead. We propose a new, more efficient algorithm to align slots. Based on geometrical properties of space, we prove that our approach bounds the slot duration by only a constant factor of what is needed. Furthermore, we show by simulation that this bound is loose and an even smaller slot duration is required, making our approach even more efficient.

Intersubject Regularity in the Intrinsic Shape of Human V1

Previous studies have reported considerable intersubject variability in the three-dimensional geometry of the human primary visual cortex (V1). Here we demonstrate that much of this variability is due to extrinsic geometric features of the cortical folds, and that the intrinsic shape of V1 is similar across individuals. V1 was imaged in ten ex vivo human hemispheres using high-resolution (200 μm) structural magnetic resonance imaging at high field strength (7 T). Manual tracings of the stria of Gennari were used to construct a surface representation, which was computationally flattened into the plane with minimal metric distortion. The instrinsic shape of V1 was determined from the boundary of the planar representation of the stria. An ellipse provided a simple parametric shape model that was a good approximation to the boundary of flattened V1. The aspect ration of the best-fitting ellipse was found to be consistent across subject, with a mean of 1.85 and standard deviation of 0.12. Optimal rigid alignment of size-normalized V1 produced greater overlap than that achieved by previous studies using different registration methods. A shape analysis of published macaque data indicated that the intrinsic shape of macaque V1 is also stereotyped, and similar to the human V1 shape. Previoud measurements of the functional boundary of V1 in human and macaque are in close agreement with these results.

A Biomechanical Model of Human Oculomotor Plant Kinematics Based Upon Geometric Algebra

A biomechanical model of the human oculomotor plant kinematics in 3-D as a function of muscle length changes is presented. It can represent a range of alternative interpretations of the data as a function of one parameter. The model is free from such deficits as singularities and the nesting of axes found in alternative formulations such as the spherical wrist (Paul, l98l). The equations of motion are defined on a quaternion based representation of eye rotations and are compact atnd computationally efficient.