Neurological impairment in nephropathic cystinosis: motor coordination deficits

Nephropathic cystinosis is a rare genetic metabolic disorder that results in accumulation of the amino acid cystine in lysosomes due to lack of a cystine-specific transporter protein. Cystine accumulates in cells throughout the body and causes progressive damage to multiple organs, including the brain. Neuromotor deficits have been qualitatively described in individuals with cystinosis. This study quantitatively examined fine-motor coordination in individuals with cystinosis. Brain magnetic resonance imaging (MRI) scans were also performed to determine whether structural changes were associated with motor deficits. Participants were 52 children and adolescents with infantile nephropathic cystinosis and 49 controls, ages 2–17 years, divided into preacademic and school-age groups. Results indicated that both the preacademic and school-age cystinosis groups performed significantly more poorly than their matched control groups on the Motor Coordination Test. Further, the level of performance was not significantly different between the preacademic and school-age groups. There were no significant differences in motor coordination scores based on MRI findings. This is the first study to document a persistent, nonprogressive, fine-motor coordination deficit in children and adolescents with cystinosis. The fact that these difficulties are present in the preschool years lends further support to the theory that cystinosis adversely affects neurological functioning early in development. The absence of a relationship between brain structural changes and motor function suggests that an alternative cause for motor dysfunction must be at work in this disorder

Exposure-age constraints on the extent, timing and rate of retreat of the last Irish Sea ice stream

We report 23 cosmogenic isotope exposure ages (10Be and 36Cl) relating to the maximum extent and deglaciation chronology of the Irish Sea Ice Stream (ISIS), which drained the SW sector of the last British-Irish Ice Sheet. These show that the ISIS failed to reach the Preseli Hills of North Pembrokeshire yet extended southwards to impinge on northern Isles of Scilly (50°N) during the last glacial maximum. Four samples from western Anglesey demonstrate deglaciation of the southern Irish Sea Basin by c. 20-18 ka, and two from the Llŷn Peninsula in northwest Wales, if valid, suggest deglaciation by c. 23-22 ka followed by gradual oscillatory northwards retreat of the ice margin for over 3000 years. An alternative interpretation of our data suggests that ice reached Scilly as late as 22-21 ka then retreated 450 km northwards within the following three millennia, possibly in response to sea level rise and/or intrinsic reorganisation within the last British-Irish Ice Sheet. Samples from upland source areas of the ISIS in NW England and SW Scotland produced exposure ages ≤14.3 ka, suggesting possible persistence of ice in such areas into the Lateglacial Interstade of 14.7-12.9 ka

X-ray He-like ions diagnostics: New Computations for Photoionized Plasmas: I. preliminary considerations

Using the new version of the photoionization code Titan designed for plane-parallel photoionized thick hot media, which is unprecedented from the point of view of line transfer, we have undertaken a study of the influence of different parameters on the He-like and H-like emission of a medium photoionized by an X-ray source. We explain why in modelling the emitting medium it is important to solve in a self-consistent way the thermal and ionization equilibria and to take into account the interconnection between the different ions. We give the equivalent widths of the sum of the He-like triplets and the triplet intensity ratios $G$ and $R$, for the most important He-like ions, for a range of density, column density, and ionization parameter, in the case of constant density media. We show that the line intensities from a given ion can be accounted for, either by small values of both the column density and of the ionization parameter, or by large values of both quantities, and it is necessary to take into account several ions to disentangle these possibilities. We show also that a "pure recombination spectrum" almost never exists in a photoionized medium: either it is thin, and resonance lines are formed by radiative excitation, or it is thick, and free-bound absorption destroys the resonance photons as they undergo resonant diffusion.Comment: 19 pages, 14 figures, accepted in A &

Mid- and Far-infrared Luminosity Functions and Galaxy Evolution from Multiwavelength Spitzer Observations up to z~2.5

[Abridged]We exploit a large homogeneous dataset to derive a self-consistent picture of IR emission based on the time-dependent 24, 15, 12 and 8micron monochromatic and bolometric IR luminosity functions (LF) over the 0<z<2.5 redshift range. Our analysis is based on the combination of data from deep Spitzer surveys in the VVDS-SWIRE and GOODS areas. To our limiting flux of S(24)=400microJy our derived sample in VVDS-SWIRE includes 1494 sources, and 666 and 904 sources brighter than S(24)=80microJy are catalogued in GOODS-S and GOODS-N, respectively, for a total area of ~0.9 square degs. We obtain reliable optical identifications and redshifts, providing us a rich and robust dataset for our luminosity function determination. Based on the multi-wavelength information available, we constrain the LFs at 8, 12, 15 and 24micron. We also extrapolate total IR luminosities from our best-fit to the observed SEDs of each source, and use this to derive the bolometric LF and comoving volume emissivity up to z~2.5. In the 0<z<1 interval, the bolometric IR luminosity density evolves as (1+z)^3.8+/-0.4. Although more uncertain at higher-z, our results show a flattening of the IR luminosity density at z>1. The mean redshift of the peak in the source number density shifts with luminosity: the brighest IR galaxies appear to be forming stars earlier in cosmic time (z>1.5), while the less luminous ones keep doing it at more recent epochs (z~1 for L(IR)<10^11L_sun). Our results suggest a rapid increase of the galaxy IR comoving volume emissivity back to z~1 and a constant average emissivity at z>1. We also seem to find a difference in the evolution rate of the source number densities as a function of luminosity, a downsizing evolutionary pattern similar to that reported from other samples of cosmic sources.Comment: Accepted for pubblicantion in Astronomy and Astrophysic

Identifying Luminous AGN in Deep Surveys: Revised IRAC Selection Criteria

Spitzer IRAC selection is a powerful tool for identifying luminous AGN. For deep IRAC data, however, the AGN selection wedges currently in use are heavily contaminated by star-forming galaxies, especially at high redshift. Using the large samples of luminous AGN and high-redshift star-forming galaxies in COSMOS, we redefine the AGN selection criteria for use in deep IRAC surveys. The new IRAC criteria are designed to be both highly complete and reliable, and incorporate the best aspects of the current AGN selection wedges and of infrared power-law selection while excluding high redshift star-forming galaxies selected via the BzK, DRG, LBG, and SMG criteria. At QSO-luminosities of log L(2-10 keV) (ergs/s) > 44, the new IRAC criteria recover 75% of the hard X-ray and IRAC-detected XMM-COSMOS sample, yet only 38% of the IRAC AGN candidates have X-ray counterparts, a fraction that rises to 52% in regions with Chandra exposures of 50-160 ks. X-ray stacking of the individually X-ray non-detected AGN candidates leads to a hard X-ray signal indicative of heavily obscured to mildly Compton-thick obscuration (log N_H (cm^-2) = 23.5 +/- 0.4). While IRAC selection recovers a substantial fraction of luminous unobscured and obscured AGN, it is incomplete to low-luminosity and host-dominated AGN.Comment: 22 pages, 15 figures, accepted for publication in ApJ, full resolution version available at http://www.stsci.edu/~donley/iragn_paper

Using the past to constrain the future: how the palaeorecord can improve estimates of global warming

Climate sensitivity is defined as the change in global mean equilibrium temperature after a doubling of atmospheric CO2 concentration and provides a simple measure of global warming. An early estimate of climate sensitivity, 1.5-4.5{\deg}C, has changed little subsequently, including the latest assessment by the Intergovernmental Panel on Climate Change. The persistence of such large uncertainties in this simple measure casts doubt on our understanding of the mechanisms of climate change and our ability to predict the response of the climate system to future perturbations. This has motivated continued attempts to constrain the range with climate data, alone or in conjunction with models. The majority of studies use data from the instrumental period (post-1850) but recent work has made use of information about the large climate changes experienced in the geological past. In this review, we first outline approaches that estimate climate sensitivity using instrumental climate observations and then summarise attempts to use the record of climate change on geological timescales. We examine the limitations of these studies and suggest ways in which the power of the palaeoclimate record could be better used to reduce uncertainties in our predictions of climate sensitivity.Comment: The final, definitive version of this paper has been published in Progress in Physical Geography, 31(5), 2007 by SAGE Publications Ltd, All rights reserved. \c{opyright} 2007 Edwards, Crucifix and Harriso

Bioarchaeology aids the cultural understanding of six characters in search of their agency (Tarquinia, ninth–seventh century BC, central Italy)

Etruria contained one of the great early urban civilisations in the Italian peninsula during the first millennium BC, much studied from a cultural, humanities-based, perspective, but relatively little with scientific data, and rarely in combination. We have addressed the unusual location of twenty inhumations found in the sacred heart of the Etruscan city of Tarquinia, focusing on six of these as illustrative, contrasting with the typical contemporary cremations found in cemeteries on the edge of the city. The cultural evidence suggests that the six skeletons were also distinctive in their ritualization and memorialisation. Focusing on the six, as a representative sample, the scientific evidence of osteoarchaeology, isotopic compositions, and ancient DNA has established that these appear to show mobility, diversity and violence through an integrated bioarchaeological approach. The combination of multiple lines of evidence makes major strides towards a deeper understanding of the role of these extraordinary individuals in the life of the early city of Etruria

High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny