Geochemistry, minerals, color, rare earth elements and d18O at DSDP Hole 92-504B

Investigations of borehole waters sampled in Hole 504B during Leg 92 revealed changes in major-ion composition similar to changes observed previously (during Leg 83). The uniformity of chloride concentrations with increasing depth suggests efficient downhole mixing processes along density gradients caused by large temperature gradients. Chemical and mineralogical studies of suspended drilling mud (bentonite) suggest that this material has undergone substantial alteration and that CaSO4 (anhydrite/gypsum) has precipitated in the deeper parts of the hole. Rare earth element studies suggest contributions of both the bentonites and the basalts to the REE distributions. Studies of the isotopic composition (87Sr/86Sr) of dissolved strontium indicate a strong contribution of basaltic nonradiogenic strontium, although differences between the Leg 83 and Leg 92 data indicate an influence of bentonite during Leg 92. The oxygen isotope composition of the water does not change appreciably downhole. This uniformity can be understood in terms of high water-rock ratios and suggests that the chemical changes observed are due either to alteration processes involving bentonites and basaltic material from the walls of the hole or to exchange with formation fluids from the surrounding basement, which may have altered in composition at relatively high water-rock ratios.

Operator's manual : decontaminating kit, skin, M291.

"October 1989."

A genome scan for eye color in 502 twin families: Most variation is due to a QTL on chromosome 15q

We have rated eye color on a 3-point scale (1=blue/grey, 2=hazel/green, 3=brown) in 502 twin families and carried out a 5-10 cM genome scan (400-757 markers). We analyzed eye color as a threshold trait and performed multipoint sib pair linkage analysis using variance components analysis in Mx. A lod of 19.2 was found at the marker D15S1002, less than 1 cM from OCA2, which has been previously implicated in eye color variation. We estimate that 74% of variance in eye color liability is due to this QTL and a further 18% due to polygenic effects. However, a large shoulder on this peak suggests that other loci affecting eye color may be telomeric of OCA2 and inflating the QTL estimate. No other peaks reached genome-wide significance, although lods >2 were seen on 5p and 14q and lods >1 were additionally seen on chromosomes 2, 3, 6, 7, 8, 9, 17 and 18. Most of these secondary peaks were reduced or eliminated when we repeated the scan as a two locus analysis with the 15q linkage included, although this does not necessarily exclude them as false positives. We also estimated the interaction between the 15q QTL and the other marker locus but there was only minor evidence for additive x additive epistasis. Elaborating the analysis to the full two-locus model including non-additive main effects and interactions did not strengthen the evidence for epistasis. We conclude that most variation in eye color in Europeans is due to polymorphism in OCA2 but that there may be modifiers at several other loci.

Mapping hippocampal and ventricular change in Alzheimer disease

We developed an anatomical mapping technique to detect hippocampal and ventricular changes in Alzheimer disease (AD). The resulting maps are sensitive to longitudinal changes in brain structure as the disease progresses. An anatomical surface modeling approach was combined with surface-based statistics to visualize the region and rate of atrophy in serial MRI scans and isolate where these changes link with cognitive decline. Fifty-two high-resolution MRI scans were acquired from 12 AD patients (age: 68.4 +/- 1.9 years) and 14 matched controls (age: 71.4 +/- 0.9 years), each scanned twice (2.1 +/- 0.4 years apart). 3D parametric mesh models of the hippocampus and temporal horns were created in sequential scans and averaged across subjects to identify systematic patterns of atrophy. As an index of radial atrophy, 3D distance fields were generated relating each anatomical surface point to a medial curve threading down the medial axis of each structure. Hippocampal atrophic rates and ventricular expansion were assessed statistically using surface-based permutation testing and were faster in AD than in controls. Using color-coded maps and video sequences, these changes were visualized as they progressed anatomically over time. Additional maps localized regions where atrophic changes linked with cognitive decline. Temporal horn expansion maps were more sensitive to AD progression than maps of hippocampal atrophy, but both maps correlated with clinical deterioration. These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials. (C) 2004 Elsevier Inc. All rights reserved.

Skin exposure during conventional phototherapy in preterm infants: A randomized controlled trial

Objective: To assess the effect of reduced skin exposure in preterm infants receiving overhead phototherapy treatment on total serum bilirubin (TSB). Methods: Randomized controlled trial. Preterm infants (>1500 g birthweight and less than or equal to 36 weeks gestation) were randomized to being nursed either partially clothed with only disposable nappies and in posturally supported positions (n = 30) or naked without postural support (n = 29). Primary outcome was mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment (irradiance of 6 muWcm(-2)/nm at a wavelength of 425-475 nm). The incidence of rebound jaundice, number of infants continuing to receive phototherapy treatment at 24 h periods, parental stress, mother-infant interaction and mean TSB percentage change at 24 h of completed conventional overhead phototherapy treatment were examined. Results: Mean TSB percentage change at 24 h of completed treatment for the partially clothed group was 15.4% (+/-18) and for the naked group 19% (+/-15) (mean difference 3.6% 95% CI -5.1, 12.3). No other outcomes were significantly affected by reduced skin exposure to overhead phototherapy treatment. Conclusion: Our results show no statistically significant difference in TSB level change using either nursing practice.

Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk

The human melanocortin-1 receptor gene (MC1R) encodes a G-protein coupled receptor that is primarily expressed on melanocytes, where it plays a key role in pigmentation regulation. Variant alleles are associated with red hair colour and fair skin, known as the RHC phenotype, as well as skin cancer risk. The R151C, R160W and D294H alleles, designated 'R', are strongly associated with the RHC phenotype and have been proposed to result in loss of function receptors due to impaired G-protein coupling. We recently provided evidence that the R151C and R160W variants can efficiently couple to G-proteins in response to alpha-melanocyte stimulating hormone. The possibility that altered cellular localization of the R151C and R160W variant receptors could underlie their association with RHC was therefore considered. Using immunofluorescence and ligand binding studies, we found that melanocytic cells exogenously or endogenously expressing MC1R show strong surface localization of the wild-type and D294H alleles but markedly reduced cell surface expression of the R151C and R160W receptors. In additional exogenous expression studies, the R variant D84E and the rare I155T variant, also demonstrated a significant reduction in plasma membrane receptor numbers. The V60L, V92M and R163Q weakly associated RHC alleles, designated 'r', were expressed with normal or intermediate cell surface receptor levels. These results indicate that reduced receptor coupling activity may not be the only contributing factor to the genetic association between the MC1R variants and the RHC phenotype, with MC1R polymorphisms now linked to a change in receptor localization.