Language trees with sampled ancestors support a hybrid model for the origin of Indo-European languages.

The origins of the Indo-European language family are hotly disputed. Bayesian phylogenetic analyses of core vocabulary have produced conflicting results, with some supporting a farming expansion out of Anatolia ~9000 years before present (yr B.P.), while others support a spread with horse-based pastoralism out of the Pontic-Caspian Steppe ~6000 yr B.P. Here we present an extensive database of Indo-European core vocabulary that eliminates past inconsistencies in cognate coding. Ancestry-enabled phylogenetic analysis of this dataset indicates that few ancient languages are direct ancestors of modern clades and produces a root age of ~8120 yr B.P. for the family. Although this date is not consistent with the Steppe hypothesis, it does not rule out an initial homeland south of the Caucasus, with a subsequent branch northward onto the steppe and then across Europe. We reconcile this hybrid hypothesis with recently published ancient DNA evidence from the steppe and the northern Fertile Crescent.

Trace element proxies and stable isotopes used to identify water quality threats to elkhorn coral (Acropora palmata) at two national parks in St. Croix, USVI.

Biological impairments have been documented on reefs at two national parks in St. Croix, USVI. Although several water quality parameters have been out of compliance with USVI criteria, whether these parameters or other pollutants are responsible for coral health impacts is unknown. Trace elements quantified in sediment showed four sites at SARI, which is closer than BUIS to settlements and land-derived anthropogenic outflows, had Cu mass fractions above sediment quality guidelines for invertebrate toxicity. Trace elements were also analyzed in the skeleton of threatened elkhorn coral, Acropora palmata, to evaluate potential exposure. Heavy metals (Pb, Zn) were significantly greater in coral skeleton at SARI than BUIS. Cu, Pb, and Zn may be impacting coral health in these parks. Potential anthropogenic sources of these metals were revealed by the coral tissue stable isotope levels (δ13C and δ15N). These findings provide a framework for determining heavy metal impacts on these invaluable reefs.

The Current Genomic Landscape of Western South America: Andes, Amazonia, and Pacific Coast.

Studies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most widely spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here, we explore the genetic structure of 176 individuals from these three domains, genotyped with the Affymetrix Human Origins array. We infer multiple sources of ancestry within the Native American ancestry component; one with clear predominance on the Coast and in the Andes, and at least two distinct substrates in neighboring Amazonia, including a previously undetected ancestry characteristic of northern Ecuador and Colombia. Amazonian populations are also involved in recent gene-flow with each other and across ecogeographic domains, which does not accord with the traditional view of small, isolated groups. Long-distance genetic connections between speakers of the same language family suggest that indigenous languages here were spread not by cultural contact alone. Finally, Native American populations admixed with post-Columbian European and African sources at different times, with few cases of prolonged isolation. With our results we emphasize the importance of including understudied regions of the continent in high-resolution genetic studies, and we illustrate the potential of SNP chip arrays for informative regional-scale analysis.

A DREAM Challenge to Build Prediction Models for Short-Term Discontinuation of Docetaxel in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Docetaxel has a demonstrated survival benefit for patients with metastatic castration-resistant prostate cancer (mCRPC); however, 10% to 20% of patients discontinue docetaxel prematurely because of toxicity-induced adverse events, and the management of risk factors for toxicity remains a challenge. PATIENTS AND METHODS: The comparator arms of four phase III clinical trials in first-line mCRPC were collected, annotated, and compiled, with a total of 2,070 patients. Early discontinuation was defined as treatment stoppage within 3 months as a result of adverse treatment effects; 10% of patients discontinued treatment. We designed an open-data, crowd-sourced DREAM Challenge for developing models with which to predict early discontinuation of docetaxel treatment. Clinical features for all four trials and outcomes for three of the four trials were made publicly available, with the outcomes of the fourth trial held back for unbiased model evaluation. Challenge participants from around the world trained models and submitted their predictions. Area under the precision-recall curve was the primary metric used for performance assessment. RESULTS: In total, 34 separate teams submitted predictions. Seven models with statistically similar area under precision-recall curves (Bayes factor ≤ 3) outperformed all other models. A postchallenge analysis of risk prediction using these seven models revealed three patient subgroups: high risk, low risk, or discordant risk. Early discontinuation events were two times higher in the high-risk subgroup compared with the low-risk subgroup. Simulation studies demonstrated that use of patient discontinuation prediction models could reduce patient enrollment in clinical trials without the loss of statistical power. CONCLUSION: This work represents a successful collaboration between 34 international teams that leveraged open clinical trial data. Our results demonstrate that routinely collected clinical features can be used to identify patients with mCRPC who are likely to discontinue treatment because of adverse events and establishes a robust benchmark with implications for clinical trial design.

Mobility and Navigation among the Yucatec Maya: Sex Differences Reflect Parental Investment, Not Mating Competition.

Sex differences in range size and navigation are widely reported, with males traveling farther than females, being less spatially anxious, and in many studies navigating more effectively. One explanation holds that these differences are the result of sexual selection, with larger ranges conferring mating benefits on males, while another explanation focuses on greater parenting costs that large ranges impose on reproductive-aged females. We evaluated these arguments with data from a community of highly monogamous Maya farmers. Maya men and women do not differ in distance traveled over the region during the mate-seeking years, suggesting that mating competition does not affect range size in this monogamous population. However, men's regional and daily travel increases after marriage, apparently in pursuit of resources that benefit families, whereas women reduce their daily travel after marriage. This suggests that parental effort is more important than mating effort in this population. Despite the relatively modest overall sex difference in mobility, Maya men were less spatially anxious than women, thought themselves to be better navigators, and pointed more accurately to distant locations. A structural equation model showed that the sex by marital status interaction had a direct effect on mobility, with a weaker indirect effect of sex on mobility mediated by navigational ability.

Effect of contrast and gaps between Vernier stimulus elements on sweep visual evoked potential measurements of human cortical Vernier responses

The present paper focuses on a classic hyperacuity, Vernier acuity-the ability to discriminate breaks in the collinearity of lines or edges on the order of only arcseconds of visual angle. We measured steady-state sweep visual evoked potentials (sVEPs) in response to 6 Hz periodic breaks in collinearity (Vernier offsets) in horizontal squarewave gratings. Vernier thresholds, estimated by extrapolating the amplitude of the first harmonic (1F) to 0 µV, were measured for gratings with 4%, 8%, 16%, 32%, 64%, and 80% contrast, with gaps of 0, 2, or 5 arcmin introduced between neighboring bar elements that formed the Vernier offsets. Thresholds for the 2F response component provided an estimate of motion thresholds. The data confirmed and extended evidence that the odd- and even-harmonic components reflect cortical activity of different neurons (i.e., neurons that respond asymmetrically to the periodic breaks in alignment and neurons that respond symmetrically to the local relative motion cue of the stimulus). Suprathreshold data (peak amplitude, response slope, and response phase at the peak amplitude) provided additional independent evidence of this notion. Vernier thresholds decreased linearly as contrast increased, with a slope of approximately -0.5 on log-log axes, similar to prior psychophysical results. The form of contrast dependence showed more similarity to measures of magnocellular ganglion cell spatial precision than measures from parvocellular ganglion cells. Our data thus support the hypothesis that magnocellular ganglion cell output from the retina has the requisite properties to support cortical calculation of Vernier offsets at a hyperacuity level...

Effect of contrast and gaps between Vernier stimulus elements on sweep visual evoked potential measurements of human cortical Vernier responses

The present paper focuses on a classic hyperacuity, Vernier acuity-the ability to discriminate breaks in the collinearity of lines or edges on the order of only arcseconds of visual angle. We measured steady-state sweep visual evoked potentials (sVEPs) in response to 6 Hz periodic breaks in collinearity (Vernier offsets) in horizontal squarewave gratings. Vernier thresholds, estimated by extrapolating the amplitude of the first harmonic (1F) to 0 µV, were measured for gratings with 4%, 8%, 16%, 32%, 64%, and 80% contrast, with gaps of 0, 2, or 5 arcmin introduced between neighboring bar elements that formed the Vernier offsets. Thresholds for the 2F response component provided an estimate of motion thresholds. The data confirmed and extended evidence that the odd- and even-harmonic components reflect cortical activity of different neurons (i.e., neurons that respond asymmetrically to the periodic breaks in alignment and neurons that respond symmetrically to the local relative motion cue of the stimulus). Suprathreshold data (peak amplitude, response slope, and response phase at the peak amplitude) provided additional independent evidence of this notion. Vernier thresholds decreased linearly as contrast increased, with a slope of approximately -0.5 on log-log axes, similar to prior psychophysical results. The form of contrast dependence showed more similarity to measures of magnocellular ganglion cell spatial precision than measures from parvocellular ganglion cells. Our data thus support the hypothesis that magnocellular ganglion cell output from the retina has the requisite properties to support cortical calculation of Vernier offsets at a hyperacuity level.(AU)

Infant growth and the thymus: data from two South American native societies.

The thymus plays an important role in the development of the immune system, yet little is known about the patterns and sources of variation in postnatal thymic development. The aim of this study is to contribute cross-cultural data on thymus size in infants from two South American native populations, the Tsimane of Bolivia and the Pumé of Venezuela. Thymic ultrasonography was performed and standard anthropometric measures collected from 86 Tsimane and Pumé infants. Patterns of infant growth and thymus size were compared between the two populations and the relationship between nutritional status and thymus size was assessed. Despite nearly identical anthropometric trajectories, Tsimane infants had larger thymuses than Pumé infants at all ages. Population, infant age, and infant mid-upper arm circumference were significant predictors of thymus area in the Tsimane and Pumé infants. This finding reveals a cross-cultural difference in thymus size that is not driven by nutritional status. We suggest that future studies focus on isolating prenatal and postnatal environmental factors underlying cross-cultural variation in thymic development.

Postmarital residence and bilateral kin associations among hunter-gatherers: Pumé foragers living in the best of both worlds.

Dispersal of individuals from their natal communities at sexual maturity is an important determinant of kin association. In this paper we compare postmarital residence patterns among Pumé foragers of Venezuela to investigate the prevalence of sex-biased vs. bilateral residence. This study complements cross-cultural overviews by examining postmarital kin association in relation to individual, longitudinal data on residence within a forager society. Based on cultural norms, the Pumé have been characterized as matrilocal. Analysis of Pumé marriages over a 25-year period finds a predominant pattern of natalocal residence. We emphasize that natalocality, bilocality, and multilocality accomplish similar ends in maximizing bilateral kin affiliations in contrast to sex-biased residential patterns. Bilateral kin association may be especially important in foraging economies where subsistence activities change throughout the year and large kin networks permit greater potential flexibility in residential mobility.

Juvenile subsistence effort, activity levels, and growth patterns. Middle childhood among Pumé foragers.

Attention has been given to cross-cultural differences in adolescent growth, but far less is known about developmental variability during juvenility (ages 3-10). Previous research among the Pumé, a group of South American foragers, found that girls achieve a greater proportion of their adult stature during juvenility compared with normative growth expectations. To explain rapid juvenile growth, in this paper we consider girls' activity levels and energy expended in subsistence effort. Results show that Pumé girls spend far less time in subsistence tasks in proportion to their body size compared with adults, and they have lower physical activity levels compared with many juveniles cross-culturally. Low activity levels help to explain where the extra energy comes from to support rapid growth in a challenging environment. We suggest that activity levels are important to account for the variation of resource and labor transfers in mediating energy availability.

Effects of age and optical blur on real depth stereoacuity.

Stereoscopic depth perception utilizes the disparity cues between the images that fall on the retinae of the two eyes. The purpose of this study was to determine what role aging and optical blur play in stereoscopic disparity sensitivity for real depth stimuli. Forty-six volunteers were tested ranging in age from 15 to 60 years. Crossed and uncrossed disparity thresholds were measured using white light under conditions of best optical correction. The uncrossed disparity thresholds were also measured with optical blur (from +1.0D to +5.0D added to the best correction). Stereothresholds were measured using the Frisby Stereo Test, which utilizes a four-alternative forced-choice staircase procedure. The threshold disparities measured for young adults were frequently lower than 10 arcsec, a value considerably lower than the clinical estimates commonly obtained using Random Dot Stereograms (20 arcsec) or Titmus Fly Test (40 arcsec) tests. Contrary to previous reports, disparity thresholds increased between the ages of 31 and 45 years. This finding should be taken into account in clinical evaluation of visual function of older patients. Optical blur degrades visual acuity and stereoacuity similarly under white-light conditions, indicating that both functions are affected proportionally by optical defocus.

Synchrony between growth and reproductive patterns in human females: Early investment in growth among Pumé foragers.

Life history is an important framework for understanding many aspects of ontogeny and reproduction relative to fitness outcomes. Because growth is a key influence on the timing of reproductive maturity and age at first birth is a critical demographic variable predicting lifetime fertility, it raises questions about the synchrony of growth and reproductive strategies. Among the Pumé, a group of South American foragers, young women give birth to their first child on average at age 15.5. Previous research showed that this early age at first birth maximizes surviving fertility under conditions of high infant mortality. In this study we evaluate Pumé growth data to test the expectation that if early reproduction is advantageous, then girls should have a developmental trajectory that best prepares them for young childbearing. Analyses show that comparatively Pumé girls invest in skeletal growth early, enter puberty having achieved a greater proportion of adult body size and grow at low velocities during adolescence. For early reproducers growing up in a food-limited environment, a precocious investment in growth is advantageous because juveniles have no chance of pregnancy and it occurs before the onset of the competing metabolic demands of final reproductive maturation and childbearing. Documenting growth patterns under preindustrial energetic and demographic conditions expands the range of developmental variation not otherwise captured by normative growth standards and contributes to research on human phenotypic plasticity in diverse environments.

The Jitter Spatial Frequency Sweep VEP: a new paradigm to study spatiotemporal development of pattern - and motion - processing mechanisms in human infants

We introduce a new VEP paradigm - the Jitter Spatial Frequency (JSF) Sweep VEP - that permits efficient mapping of the spatiotemporal tuning of the developmental motion asymmetry (DMA). Vertical sinewave gratings undergoing 90º horizontal oscillatory displacements (6 or 10 Hz) were presented while their SF was swept over 2 to 5 octaves during each VEP trial. JSF sweep VEPs were recorded from 28 infants (8-43 weeks), and symmetric (second-harmonic, F2) and asymmetric (F1) components of the VEP were measured. JSF sweeps can provide four useful estimates: (1,2) the high-SF cutoff of F1 and F2 responses estimates the spatial resolution of direction-selective (DS) and non-DS mechanisms, respectively; (3) the low-SF cutoff for F1 estimate the SF-boundary between mature (F1 absent) and immature (F1 present) DS mechanisms; and (4) the F1 high-SF cutoff estimates the lower velocity limit of cortical DS cells. For 6 Hz, the low-SF F1 cutoffs increased two times faster than traditional (contrast-reversal) VEP grating acuity (0.5 vs ~0.25 octaves/month), and twice that of the high-SF F1 and F2 cutoffs. This implies that no single mechanism can account for the DMA at both low and high SFs. At 10 Hz, the DMA exhibited no significant development, consistent with slower maturation of DS mechanisms at higher ST frequencies. The F2 high-SF cutoffs were higher than F1 at both 6 and 10 Hz, suggesting higher spatial resolution for non-DS (pattern) vs DS (motion) mechanisms. Finally, the lower velocity limit of the DS mechanisms decreased from ~2 deg/sec at 8 weeks, to 0.75 deg/sec at 33 weeks, similar to analogous limits for direction-of-motion identification in adults (~0.5 - 1 deg/sec), and close to prior VEP estimates in infants (0.6 deg/sec).

The Jitter Spatial Frequency Sweep VEP: a new paradigm to study spatiotemporal development of pattern- and motion-processing mechanisms in human infants

We introduce a new VEP paradigm - the Jitter Spatial Frequency (JSF) Sweep VEP - that permits efficient mapping of the spatiotemporal tuning of the developmental motion asymmetry (DMA). Vertical sinewave gratings undergoing 90º horizontal oscillatory displacements (6 or 10 Hz) were presented while their SF was swept over 2 to 5 octaves during each VEP trial. JSF sweep VEPs were recorded from 28 infants (8-43 weeks), and symmetric (second-harmonic, F2) and asymmetric (F1) components of the VEP were measured. JSF sweeps can provide four useful estimates: (1,2) the high-SF cutoff of F1 and F2 responses estimates the spatial resolution of direction-selective (DS) and non-DS mechanisms, respectively; (3) the low-SF cutoff for F1 estimate the SF-boundary between mature (F1 absent) and immature (F1 present) DS mechanisms; and (4) the F1 high-SF cutoff estimates the lower velocity limit of cortical DS cells. For 6 Hz, the low-SF F1 cutoffs increased two times faster than traditional (contrast-reversal) VEP grating acuity (0.5 vs ~0.25 octaves/month), and twice that of the high-SF F1 and F2 cutoffs. This implies that no single mechanism can account for the DMA at both low and high SFs. At 10 Hz, the DMA exhibited no significant development, consistent with slower maturation of DS mechanisms at higher ST frequencies. The F2 high-SF cutoffs were higher than F1 at both 6 and 10 Hz, suggesting higher spatial resolution for non-DS (pattern) vs DS (motion) mechanisms. Finally, the lower velocity limit of the DS mechanisms decreased from ~2 deg/sec at 8 weeks, to 0.75 deg/sec at 33 weeks, similar to analogous limits for direction-of-motion identification in adults (~0.5 - 1 deg/sec), and close to prior VEP estimates in infants (0.6 deg/sec).(AU)

WITHDRAWN: Communication between immune cells mediated by membrane connections.

This article has been withdrawn at the request of the authors and Guest Editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Chromatic discrimination losses in multiple sclerosis patients with and without optic neuritis using the Cambridge Colour Test.

We assessed chromatic discrimination in multiple sclerosis (MS) patients both with (ON) and without (no ON) a history of optic neuritis using the Cambridge color test (CCT). Our goal was to determine the magnitude and chromatic axes of any color vision losses in both patient groups, and to evaluate age-related changes in chromatic discrimination in both patient groups compared to normals. Using the CCT, we measured chromatic discrimination along the protan, deutan and tritan axes in 35 patients with MS (17 ON eyes) and 74 age matched controls. Color thresholds for both patient groups were significantly higher than controls' along the protan and tritan axes (p < 0.001). In addition, the ON and no-ON groups differed significantly along all three-color axes (p < 0.001). MS patients presented a progressive color discrimination impairment with age (along the deutan and tritan axes) that was almost two times faster than controls, even in the absence of ON. These findings suggest that demyelinating diseases reduce sensitivity to color vision in both red-green and blue-yellow axes, implying impairment in both parvocellular and koniocellular visual pathways. The CCT is a useful tool to help characterize vision losses in MS, and the relationship between these losses and degree of optic nerve involvement.

Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss.

OBJECTIVE: To determine the relationship between the virus burden in infancy and hearing loss in congenital CMV infection. STUDY DESIGN: A cohort of 76 infants with congenital cytomegalovirus (CMV) infection identified by means of newborn virologic screening was monitored for outcome. The amount of infectious CMV was analyzed in urine specimens obtained during early infancy. Peripheral blood (PB) samples obtained during early infancy were available from 75 children and CMV DNA was quantitated with a real-time quantitative polymerase chain reaction. RESULTS: Infants with clinical abnormalities at birth (symptomatic congenital CMV infection) had higher amounts of CMV in urine (P = .005) and CMV DNA in PB (P = .001) than infants with no symptoms. Eight children with and 4 children without symptoms had hearing loss. Among children without symptoms, those with hearing loss had a significantly greater amount of CMV in urine (P = .03) and PB virus burden (P = .02) during infancy than those with normal hearing. Infants with < 5 x 10(3) pfu/mL of urine CMV and infants with < 1 x 10(4) copies/mL of viral DNA in PB were at a lower risk for hearing loss. CONCLUSION: In children with asymptomatic congenital CMV infection, hearing loss was associated with increased amounts of urine CMV and PB CMV DNA during early infancy.

The relation between skeletal maturation and adiposity in African American and Caucasian children.

OBJECTIVE: African American children have earlier pubertal and skeletal maturation and a higher body mass index (BMI) than Caucasian children. We tested the hypothesis that advanced bone age in African American children is accounted for by their greater adiposity. STUDY DESIGN: We studied 252 African American (n = 97) and Caucasian (n = 155) children aged 5 to 12 years. Skeletal age was determined by a radiologist blinded to clinical details. The difference between bone age (BA) and chronological age (CA) (noted as BA - CA) and the ratio of bone age to chronological age (BA/CA) were determined. Analysis of covariance was used to adjust skeletal maturation for the effects of adiposity, as measured by BMI, BMI standard deviation score (BMI SDS), and fat mass by dual energy x-ray absorptiometry (DXA). RESULTS: African American children were significantly heavier than Caucasians (BMI SDS 2.7 +/- 3.4 vs 1.7 +/- 2.4, P <.05). Both BA - CA (0.75 +/- 1.46 vs 0.28 +/- 1.38, P <.05) and BA/CA (1.09 +/- 0.17 vs 1.03 +/- 0.16, P <.05) were significantly greater in African Americans than Caucasians. BA - CA and BA/CA were significantly correlated with lean body mass, BMI, BMI SDS, and DXA fat mass (all r > 0.46, P <.001). Neither BA - CA nor BA/CA of African Americans and Caucasians were significantly different after correction for lean body mass and measures of adiposity, including BMI, BMI SDS, or DXA fat mass. CONCLUSION: Skeletal age is more advanced in African American than Caucasian children and is significantly related to body mass. In large measure, the advancement in skeletal maturation of prepubertal and early pubertal African American children can be accounted for by their greater adiposity.

Relation of acanthosis nigricans to hyperinsulinemia and insulin sensitivity in overweight African American and white children.

OBJECTIVES: Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinism has not been systematically evaluated in overweight children. We examined the relationship of AN to hyperinsulinemia and body adiposity. STUDY DESIGN: One hundred thirty-nine children underwent physical examination for AN, body composition studies, an oral glucose tolerance test, and a hyperglycemic clamp. RESULTS: Thirty-five children (25%) had AN. AN was more prevalent in African Americans (50.1%) than in white subjects (8.2%, P < .001). Independent of race, children with AN had greater body weight and body fat mass (P < .001); greater basal and glucose-stimulated insulin levels during oral glucose tolerance test (P < .001); greater first-phase, second-phase, and steady-state insulin levels (P < .001); and lower insulin sensitivity (P < .001) during the hyperglycemic clamp. After adjusting for body fat mass and age, none of these differences remained significant. When categorized by fasting insulin, 35% with fasting insulin levels > 20 microU/mL and 50% with fasting insulin levels > 15 microU/mL did not have AN. Eighty-eight percent of children with fasting insulin levels > or = 15 microU/mL had a body mass index SD score > or = 3.0. CONCLUSIONS: AN is not a reliable marker for hyperinsulinemia in overweight children. Children with a race-, sex-, and age-specific body mass index SD scores > or = 3.0 should be screened for hyperinsulinemia, whether or not they have AN.

17Beta-hydroxysteroid dehydrogenase 3 deficiency in women.

In genetic males, mutation of the 17beta-hydroxysteroid dehydrogenase 3 (17HSD3)gene that is normally expressed in the testes impairs testosterone formation and causes development of male pseudohermaphroditism. We have ascertained seven women who are sisters of men with 17HSD3 deficiency and who are either homozygotes or compound heterozygotes for the same mutations as their affected brothers. Our findings confirm the concept that women with such mutations are asymptomatic.