Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results ...from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We used fMRI in 85 healthy participants to investigate whether different parts of the left supramarginal gyrus (SMG) are involved in processing phonological inputs and outputs. The experiment ...involved 2 tasks (speech production (SP) and one-back (OB) matching) on 8 different types of stimuli that systematically varied the demands on sensory processing (visual vs. auditory), sublexical phonological input (words and pseudowords vs. nonverbal stimuli), and semantic content (words and objects vs. pseudowords and meaningless baseline stimuli). In ventral SMG, we found an anterior subregion associated with articulatory sequencing (for SP > OB matching) and a posterior subregion associated with auditory short-term memory (for all auditory > visual stimuli and written words and pseudowords > objects). In dorsal SMG, a posterior subregion was most highly activated by words, indicating a role in the integration of sublexical and lexical cues. In anterior dorsal SMG, activation was higher for both pseudoword reading and object naming compared with word reading, which is more consistent with executive demands than phonological processing. The dissociation of these four "functionally-distinct" regions, all within left SMG, has implications for differentiating between different types of phonological processing, understanding the functional anatomy of language and predicting the effect of brain damage.
The second phase of the Fifth International Ice Nucleation Workshop (FIN-02)
involved the gathering of a large number of researchers at the Karlsruhe
Institute of Technology's Aerosol Interactions ...and Dynamics of the Atmosphere
(AIDA) facility to promote characterization and understanding of ice
nucleation measurements made by a variety of methods used worldwide.
Compared to the previous workshop in 2007, participation was doubled,
reflecting a vibrant research area. Experimental methods involved sampling of
aerosol particles by direct processing ice nucleation measuring systems from
the same volume of air in separate experiments using different ice nucleating
particle (INP) types, and collections of aerosol particle samples onto
filters or into liquid for sharing amongst measurement techniques that
post-process these samples. In this manner, any errors introduced by
differences in generation methods when samples are shared across laboratories
were mitigated. Furthermore, as much as possible, aerosol particle size
distribution was controlled so that the size limitations of different methods
were minimized. The results presented here use data from the workshop to
assess the comparability of immersion freezing measurement methods activating
INPs in bulk suspensions, methods that activate INPs in condensation and/or
immersion freezing modes as single particles on a substrate, continuous flow
diffusion chambers (CFDCs) directly sampling and processing particles well
above water saturation to maximize immersion and subsequent freezing of
aerosol particles, and expansion cloud chamber simulations in which liquid
cloud droplets were first activated on aerosol particles prior to freezing.
The AIDA expansion chamber measurements are expected to be the closest
representation to INP activation in atmospheric cloud parcels in these
comparisons, due to exposing particles freely to adiabatic cooling. The different particle types used as INPs included the minerals illite NX and
potassium feldspar (K-feldspar), two natural soil dusts representative of arable sandy loam
(Argentina) and highly erodible sandy dryland (Tunisia) soils, respectively,
and a bacterial INP (Snomax®). Considered
together, the agreement among post-processed immersion freezing measurements
of the numbers and fractions of particles active at different temperatures
following bulk collection of particles into liquid was excellent, with
possible temperature uncertainties inferred to be a key factor in determining
INP uncertainties. Collection onto filters for rinsing versus directly into
liquid in impingers made little difference. For methods that activated
collected single particles on a substrate at a controlled humidity at or
above water saturation, agreement with immersion freezing methods was good in
most cases, but was biased low in a few others for reasons that have not been
resolved, but could relate to water vapor competition effects. Amongst
CFDC-style instruments, various factors requiring (variable) higher
supersaturations to achieve equivalent immersion freezing activation dominate
the uncertainty between these measurements, and for comparison with bulk
immersion freezing methods. When operated above water saturation to include
assessment of immersion freezing, CFDC measurements often measured at or
above the upper bound of immersion freezing device measurements, but often
underestimated INP concentration in comparison to an immersion freezing
method that first activates all particles into liquid droplets prior to
cooling (the PIMCA-PINC device, or Portable Immersion Mode Cooling chAmber–Portable Ice Nucleation Chamber), and typically slightly underestimated INP
number concentrations in comparison to cloud parcel expansions in the AIDA
chamber; this can be largely mitigated when it is possible to raise the
relative humidity to sufficiently high values in the CFDCs, although this is
not always possible operationally. Correspondence of measurements of INPs among direct sampling and
post-processing systems varied depending on the INP type. Agreement was best
for Snomax® particles in the temperature regime
colder than −10 ∘C, where their ice nucleation activity is nearly
maximized and changes very little with temperature. At temperatures warmer than
−10 ∘C, Snomax® INP measurements (all
via freezing of suspensions) demonstrated discrepancies consistent with
previous reports of the instability of its protein aggregates that appear to
make it less suitable as a calibration INP at these temperatures. For
Argentinian soil dust particles, there was excellent agreement across all
measurement methods; measures ranged within 1 order of magnitude for INP
number concentrations, active fractions and calculated active site densities
over a 25 to 30 ∘C range and 5 to 8 orders of corresponding
magnitude change in number concentrations. This was also the case for all
temperatures warmer than −25 ∘C in Tunisian dust experiments. In
contrast, discrepancies in measurements of INP concentrations or active site
densities that exceeded 2 orders of magnitude across a broad range of temperature
measurements found at temperatures warmer than −25 ∘C in a previous study were
replicated for illite NX. Discrepancies also exceeded 2 orders of magnitude at
temperatures of −20 to −25 ∘C for potassium feldspar (K-feldspar), but these coincided
with the range of temperatures at which INP concentrations increase rapidly at
approximately an order of magnitude per 2 ∘C cooling for
K-feldspar. These few discrepancies did not outweigh the overall positive outcomes of the
workshop activity, nor the future utility of this data set or future similar
efforts for resolving remaining measurement issues. Measurements of the same
materials were repeatable over the time of the workshop and demonstrated
strong consistency with prior studies, as reflected by agreement of data
broadly with parameterizations of different specific or general (e.g., soil
dust) aerosol types. The divergent measurements of the INP activity of illite
NX by direct versus post-processing methods were not repeated for other
particle types, and the Snomax® data
demonstrated that, at least for a biological INP type, there is no expected
measurement bias between bulk collection and direct immediately processed
freezing methods to as warm as −10 ∘C. Since particle size ranges
were limited for this workshop, it can be expected that for atmospheric
populations of INPs, measurement discrepancies will appear due to the
different capabilities of methods for sampling the full aerosol size
distribution, or due to limitations on achieving sufficient water
supersaturations to fully capture immersion freezing in direct processing
instruments. Overall, this workshop presents an improved picture of present
capabilities for measuring INPs than in past workshops, and provides
direction toward addressing remaining measurement issues.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To determine factors associated with baseline neurocognitive performance in HIV-infected participants enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) neurology substudy.
...Participants from Australia, North America, Brazil, and Thailand were administered a 5-test neurocognitive battery. Z scores and the neurocognitive performance outcome measure, the quantitative neurocognitive performance z score (QNPZ-5), were calculated using US norms. Neurocognitive impairment was defined as z scores <-2 in two or more cognitive domains. Associations of test scores, the QNPZ-5, and impairment with baseline factors including demographics and risk factors for HIV-associated dementia (HAD) and cardiovascular disease (CVD) were determined in multiple regression.
The 292 participants had a median CD4 cell count of 536 cells/mm(3), 88% had an HIV viral load < or =400 copies/mL, and 92% were taking antiretrovirals. Demographics, HIV, and clinical factors differed between locations. The mean QNPZ-5 score was -0.72; 14% of participants had neurocognitive impairment. For most tests, scores and z scores differed significantly between locations, with and without adjustment for age, sex, education, and race. Prior CVD was associated with neurocognitive impairment. Prior CVD, hypercholesterolemia, and hypertension were associated with poorer neurocognitive performance but conventional HAD risk factors and the CNS penetration effectiveness rank of antiretroviral regimens were not.
In this HIV-positive population with high CD4 cell counts, neurocognitive impairment was associated with prior CVD. Lower neurocognitive performance was associated with prior CVD, hypertension, and hypercholesterolemia, but not conventional HAD risk factors. The contribution of CVD and cardiovascular risk factors to the neurocognition of HIV-positive populations warrants further investigation.
Language Control in the Bilingual Brain Crinion, J; Turner, R; Grogan, A ...
Science (American Association for the Advancement of Science),
06/2006, Volume:
312, Issue:
5779
Journal Article
Peer reviewed
How does the bilingual brain distinguish and control which language is in use? Previous functional imaging experiments have not been able to answer this question because proficient bilinguals ...activate the same brain regions irrespective of the language being tested. Here, we reveal that neuronal responses within the left caudate are sensitive to changes in the language or the meaning of words. By demonstrating this effect in populations of German-English and Japanese-English bilinguals, we suggest that the left caudate plays a universal role in monitoring and controlling the language in use.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass ...stimulated by nutrient inputs ('consumer-controlled'). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ('resource-controlled'). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.
The scope of adaptive phenotypic change within a lineage is shaped by how functional traits evolve. Castes are defining functional traits of adaptive phenotypic change in complex insect societies, ...and caste evolution is expected to be phylogenetically conserved and developmentally constrained at broad phylogenetic scales. Yet how castes evolve at the species level has remained largely unaddressed. Turtle ant soldiers (genus Cephalotes), an iconic example of caste specialization, defend nest entrances by using their elaborately armored heads as living barricades. Across species, soldier morphotype determines entrance specialization and defensive strategy, while head size sets the specific size of defended entrances. Our species-level comparative analyses of morphotype and head size evolution reveal that these key ecomorphological traits are extensively reversible, repeatable, and decoupled within soldiers and between soldier and queen castes. Repeated evolutionary gains and losses of the four morphotypes were reconstructed consistently across multiple analyses. In addition, morphotype did not predict mean head size across the three most common morphotypes, and head size distributions overlapped broadly across all morphotypes. Concordantly, multiple model-fitting approaches suggested that soldier head size evolution is best explained by a process of divergent pulses of change. Finally, while soldier and queen head size were broadly coupled across species, the level of head size disparity between castes was decoupled from both queen head size and soldier morphotype. These findings demonstrate that caste evolution can be highly dynamic at the species level, reshaping our understanding of adaptive morphological change in complex social lineages.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
– The fluence of dust particles <10 μm in diameter was recorded by impacts on aluminum foil of the NASA Stardust spacecraft during a close flyby of comet 81P/Wild 2 in 2004. Initial interpretation of ...craters for impactor particle dimensions and mass was based upon laboratory experimental simulations using projectiles less than >10 μm in diameter and the resulting linear relationship of projectile to crater diameter was extrapolated to smaller sizes. We now describe a new experimental calibration program firing very small monodisperse silica projectiles (470 nm–10 μm) at approximately 6 km s−1. The results show an unexpected departure from linear relationship between 1 and 10 μm. We collated crater measurement data and, where applicable, impactor residue data for 596 craters gathered during the postmission preliminary examination phase. Using the new calibration, we recalculate the size of the particle responsible for each crater and hence reinterpret the cometary dust size distribution. We find a greater flux of small particles than previously reported. From crater morphology and residue composition of a subset of craters, the internal structure and dimensions of the fine dust particles are inferred and a “maximum‐size” distribution for the subgrains composing aggregate particles is obtained. The size distribution of the small particles derived directly from the measured craters peaks at approximately 175 nm, but if this is corrected to allow for aggregate grains, the peak in subgrain sizes is at <100 nm.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and ...receptors to determine their prognostic and predictive effects.
We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population.
Patients with low expression of VEGF-D (0, 1þ) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CBþCBM), 0.21; 95% CI, 0.08–0.55; overall survival (OS) HR, 0.35; 95% CI, 0.13–0.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2þ PFS HR, 0.67; 95% CI, 0.45–1.00; OS HR, 0.82; 95% CI, 0.52–1.30; VEGF-D 3þ PFS HR, 0.77; 95% CI, 0.50–1.17; OS HR, 1.28; 95% CI, 0.79–2.09) (P interaction o0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression.
The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The study 20050181 demonstrated significant improvements in progression-free survival (PFS), objective response, and a nonsignificant trend toward increased overall survival (OS) with ...panitumumab–FOLFIRI versus FOLFIRI alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Updated long-term data from a prespecified descriptive analysis are reported.
Patients receiving one prior mCRC treatment were randomly assigned (1:1) to panitumumab (6.0 mg/kg)–FOLFIRI versus FOLFIRI every 2 weeks. Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS status.
One thousand one hundred and eighty-six patients were randomly assigned. In patients with WT KRAS tumors, panitumumab–FOLFIRI significantly improved PFS versus FOLFIRI median 6.7 versus 4.9 months; hazard ratio (HR) 0.82 95% confidence interval (CI) 0.69, 0.97; P = 0.023. A trend toward longer OS was observed (median 14.5 versus 12.5 months; HR 0.92 95% CI 0.78, 1.10; P = 0.37). Response rates improved from 10% to 36% (P < 0.0001). From post hoc analyses in patients receiving prior oxaliplatin–bevacizumab, panitumumab–FOLFIRI improved PFS (median 6.4 versus 3.7 months; HR 0.58 95% CI 0.37, 0.90; P = 0.014). PFS and OS appeared longer for worst-grade skin toxicity of 2–4, versus 0–1 or FOLFIRI. Safety results were as previously reported and consistent with the known toxicities with anti-epidermal growth factor receptor therapy.
These data confirm the primary efficacy and safety findings of this trial and support panitumumab–FOLFIRI as a second-line treatment of WT KRAS mCRC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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