Original Article

The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs) are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development.The present paper uses Early Childhood Development Index (ECDI) data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS) and Demographic and Health Surveys (DHS) programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI) and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million) in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y), followed by South Asia (27.7 million; 37.7%) and the East Asia and Pacific region (15.1 million; 25.9%). Positive associations were found between low development scores and stunting, poverty, male sex, rural residence, and lack of cognitive stimulation. Additional research using more detailed developmental assessments across a larger number of LMICs is needed to address the limitations of the present study.The number of children globally failing to reach their developmental potential remains large. Additional research is needed to identify the specific causes of poor developmental outcomes in diverse settings, as well as potential context-specific interventions that might promote children's early cognitive and socioemotional well-being

Aspects of holography for theories with hyperscaling violation

We analyze various aspects of the recently proposed holographic theories with general dynamical critical exponent z and hyperscaling violation exponent $\theta$. We first find the basic constraints on $z, \theta$ from the gravity side, and compute the stress-energy tensor expectation values and scalar two-point functions. Massive correlators exhibit a nontrivial exponential behavior at long distances, controlled by $\theta$. At short distance, the two-point functions become power-law, with a universal form for $\theta > 0$. Next, the calculation of the holographic entanglement entropy reveals the existence of novel phases which violate the area law. The entropy in these phases has a behavior that interpolates between that of a Fermi surface and that exhibited by systems with extensive entanglement entropy. Finally, we describe microscopic embeddings of some $\theta \neq 0$ metrics into full string theory models -- these metrics characterize large regions of the parameter space of Dp-brane metrics for $p\neq 3$. For instance, the theory of N D2-branes in IIA supergravity has z=1 and $\theta = -1/3$ over a wide range of scales, at large $g_s N$.Comment: 35 pages; v2: new references added; v3: proper reference [14] added; v4: minor clarification

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe

Early-Time Energy Loss in a Strongly-Coupled SYM Plasma

We carry out an analytic study of the early-time motion of a quark in a strongly-coupled maximally-supersymmetric Yang-Mills plasma, using the AdS/CFT correspondence. Our approach extracts the first thermal effects as a small perturbation of the known quark dynamics in vacuum, using a double expansion that is valid for early times and for (moderately) ultrarelativistic quark velocities. The quark is found to lose energy at a rate that differs significantly from the previously derived stationary/late-time result: it scales like T^4 instead of T^2, and is associated with a friction coefficient that is not independent of the quark momentum. Under conditions representative of the quark-gluon plasma as obtained at RHIC, the early energy loss rate is a few times smaller than its late-time counterpart. Our analysis additionally leads to thermally-corrected expressions for the intrinsic energy and momentum of the quark, in which the previously discovered limiting velocity of the quark is found to appear naturally.Comment: 39 pages, no figures. v2: Minor corrections and clarifications. References added. Version to be published in JHE

The response of Plantago major ssp pleiosperma to elevated CO2 is modulated by the formation of secondary shoots

The effect of elevated CO2 on the relative growth rate (RGR) of Plantago major ssp. pleiosperma was studied during the vegetative stage, in relation to plant development, by growing plants at 350 mu l l(-1) or at 700 mu l l(-1) CO2 in non-limiting nutrient solution with nitrate. To minimize interference by the accumulation of non-structural carbohydrates in the interpretation of results, RGR was expressed on a f. wt basis (RGR(FW)), as were all plant weight ratios. Stimulation of the RGR(FW) Of the whole plant by elevated CO2 was transient, and did not last longer than 8 d. At the same time a transient increase in root weight ratio (RWR) was observed. In order to investigate whether the transient effect of elevated CO2 on RGR(FW) was size-dependent, the data were plotted versus total f. wt (log(e) transformed). The transient period of stimulation of RGR(FW) and of RWR by elevated CO2 was still found, but in both CO2 treatments RGR(FW) decreased after a certain plant size had been reached. This size coincided with the stage at which secondary shoots started to develop, and was reached earlier in plants grown at elevated CO2. The RGR of these secondary shoots (RGR(see)) was Still increased when the period of whole plant stimulation of RGR(FW) had ended, indicating that the development of these new sinks took priority over a continuation of the stimulation of RWR. It is hypothesized that in this Plantago subspecies the response of the RGR(FW) of the whole plants to elevated CO2 is modulated by the formation of secondary shoots. Apparently, partitioning of the extra soluble carbohydrates at elevated CO2 to this tissue takes precedence over partitioning to the roots. resulting in a cessation of stimulation of plant RGR(FW) by elevated CO2.info:eu-repo/semantics/publishedVersio

Numerical study of nonlinear heat transfer from a wavy surface to a high permeability medium with pseudo-spectral and smoothed particle methods

Motivated by petro-chemical geological systems, we consider the natural convection boundary layer flow from a vertical isothermal wavy surface adjacent to a saturated non-Darcian high permeability porous medium. High permeability is considered to represent geologically sparsely packed porous media. Both Darcian drag and Forchheimer inertial drag terms are included in the velocity boundary layer equation. A high permeability medium is considered. We employ a sinusoidal relation for the wavy surface. Using a set of transformations, the momentum and heat conservation equations are converted from an (x, y) coordinate system to an (x,η) dimensionless system. The two-point boundary value problem is then solved numerically with a pseudo-spectral method based on combining the Bellman–Kalaba quasi linearization method with the Chebyschev spectral collocation technique (SQLM). The SQLM computations are demonstrated to achieve excellent correlation with smoothed particle hydrodynamic (SPH) Lagrangian solutions. We study the effect of Darcy number (Da), Forchheimer number (Fs), amplitude wavelength (A) and Prandtl number (Pr) on the velocity and temperature distributions in the regime. Local Nusselt number is also computed for selected cases. The study finds important applications in petroleum engineering and also energy systems exploiting porous media and undulating (wavy) surface geometry. The SQLM algorithm is shown to be exceptionally robust and achieves fast convergence and excellent accuracy in nonlinear heat transfer simulations

De novo domestication of wild tomato using genome editing

Breeding of crops over millennia for yield and productivity1 has led to reduced genetic diversity. As a result, beneficial traits of wild species, such as disease resistance and stress tolerance, have been lost2. We devised a CRISPR–Cas9 genome engineering strategy to combine agronomically desirable traits with useful traits present in wild lines. We report that editing of six loci that are important for yield and productivity in present-day tomato crop lines enabled de novo domestication of wild Solanum pimpinellifolium. Engineered S. pimpinellifolium morphology was altered, together with the size, number and nutritional value of the fruits. Compared with the wild parent, our engineered lines have a threefold increase in fruit size and a tenfold increase in fruit number. Notably, fruit lycopene accumulation is improved by 500% compared with the widely cultivated S. lycopersicum. Our results pave the way for molecular breeding programs to exploit the genetic diversity present in wild plants

Early Vegetation Development on an Exposed Reservoir: Implications for Dam Removal

The 4-year drawdown of Horsetooth Reservoir, Colorado, for dam maintenance, provides a case study analog of vegetation response on sediment that might be exposed from removal of a tall dam. Early vegetation recovery on the exposed reservoir bottom was a combination of (1) vegetation colonization on bare, moist substrates typical of riparian zones and reservoir sediment of shallow dams and (2) a shift in moisture status from mesic to the xeric conditions associated with the pre-impoundment upland position of most of the drawdown zone. Plant communities changed rapidly during the first four years of exposure, but were still substantially different from the background upland plant community. Predictions from the recruitment box model about the locations of Populus deltoides subsp. monilifera (plains cottonwood) seedlings relative to the water surface were qualitatively confirmed with respect to optimum locations. However, the extreme vertical range of water surface elevations produced cottonwood seed regeneration well outside the predicted limits of drawdown rate and height above late summer stage. The establishment and survival of cottonwood at high elevations and the differences between the upland plant community and the community that had developed after four years of exposure suggest that vegetation recovery following tall dam removal will follow a trajectory very different from a simple reversal of the response to dam construction, involving not only long time scales of establishment and growth of upland vegetation, but also possibly decades of persistence of legacy vegetation established during the reservoir to upland transition

Density of Common Complex Ocular Traits in the Aging Eye: Analysis of Secondary Traits in Genome-Wide Association Studies

Genetic association studies are identifying genetic risks for common complex ocular traits such as age-related macular degeneration (AMD). The subjects used for discovery of these loci have been largely from clinic-based, case-control studies. Typically, only the primary phenotype (e.g., AMD) being studied is systematically documented and other complex traits (e.g., affecting the eye) are largely ignored. The purpose of this study was to characterize these other or secondary complex ocular traits present in the cases and controls of clinic-based studies being used for genetic study of AMD. The records of 100 consecutive new patients (of any diagnosis) age 60 or older for which all traits affecting the eye had been recorded systematically were reviewed. The average patient had 3.5 distinct diagnoses. A subset of 10 complex traits was selected for further study because they were common and could be reliably diagnosed. The density of these 10 complex ocular traits increased by 0.017 log-traits/year (P = 0.03), ranging from a predicted 2.74 at age 60 to 4.45 at age 90. Trait-trait association was observed only between AMD and primary vitreomacular traction (P = 0.0009). Only 1% of subjects age 60 or older had no common complex traits affecting the eye. Extrapolations suggested that a study of 2000 similar subjects would have sufficient power to detect genetic association with an odds ratio of 2.0 or less for 4 of these 10 traits. In conclusion, the high prevalence of complex traits affecting the aging eye and the inherent biases in referral patterns leads to the potential for confounding by undocumented secondary traits within case-control studies. In addition to the primary trait, other common ocular phenotypes should be systematically documented in genetic association studies so that adjustments for potential trait-trait associations and other bias can be made and genetic risk variants identified in secondary analyses