High Effective Coverage of Vector Control Interventions in Children After Achieving Low Malaria Transmission in Zanzibar, Tanzania.

\ud \ud Formerly a high malaria transmission area, Zanzibar is now targeting malaria elimination. A major challenge is to avoid resurgence of malaria, the success of which includes maintaining high effective coverage of vector control interventions such as bed nets and indoor residual spraying (IRS). In this study, caretakers' continued use of preventive measures for their children is evaluated, following a sharp reduction in malaria transmission. A cross-sectional community-based survey was conducted in June 2009 in North A and Micheweni districts in Zanzibar. Households were randomly selected using two-stage cluster sampling. Interviews were conducted with 560 caretakers of under-five-year old children, who were asked about perceptions on the malaria situation, vector control, household assets, and intention for continued use of vector control as malaria burden further decreases. Effective coverage of vector control interventions for under-five children remains high, although most caretakers (65%; 363/560) did not perceive malaria as presently being a major health issue. Seventy percent (447/643) of the under-five children slept under a long-lasting insecticidal net (LLIN) and 94% (607/643) were living in houses targeted with IRS. In total, 98% (628/643) of the children were covered by at least one of the vector control interventions. Seasonal bed-net use for children was reported by 25% (125/508) of caretakers of children who used bed nets. A high proportion of caretakers (95%; 500/524) stated that they intended to continue using preventive measures for their under-five children as malaria burden further reduces. Malaria risk perceptions and different perceptions of vector control were not found to be significantly associated with LLIN effective coverage While the majority of caretakers felt that malaria had been reduced in Zanzibar, effective coverage of vector control interventions remained high. Caretakers appreciated the interventions and recognized the value of sustaining their use. Thus, sustaining high effective coverage of vector control interventions, which is crucial for reaching malaria elimination in Zanzibar, can be achieved by maintaining effective delivery of these interventions

Tracing chemical evolution over the extent of the Milky Way's Disk with APOGEE Red Clump Stars

We employ the first two years of data from the near-infrared, high-resolution SDSS-III/APOGEE spectroscopic survey to investigate the distribution of metallicity and alpha-element abundances of stars over a large part of the Milky Way disk. Using a sample of ~10,000 kinematically-unbiased red-clump stars with ~5% distance accuracy as tracers, the [alpha/Fe] vs. [Fe/H] distribution of this sample exhibits a bimodality in [alpha/Fe] at intermediate metallicities, -0.9<[Fe/H]<-0.2, but at higher metallicities ([Fe/H]=+0.2) the two sequences smoothly merge. We investigate the effects of the APOGEE selection function and volume filling fraction and find that these have little qualitative impact on the alpha-element abundance patterns. The described abundance pattern is found throughout the range 5<R<11 kpc and 0<|Z|<2 kpc across the Galaxy. The [alpha/Fe] trend of the high-alpha sequence is surprisingly constant throughout the Galaxy, with little variation from region to region (~10%). Using simple galactic chemical evolution models we derive an average star formation efficiency (SFE) in the high-alpha sequence of ~4.5E-10 1/yr, which is quite close to the nearly-constant value found in molecular-gas-dominated regions of nearby spirals. This result suggests that the early evolution of the Milky Way disk was characterized by stars that shared a similar star formation history and were formed in a well-mixed, turbulent, and molecular-dominated ISM with a gas consumption timescale (1/SFE) of ~2 Gyr. Finally, while the two alpha-element sequences in the inner Galaxy can be explained by a single chemical evolutionary track this cannot hold in the outer Galaxy, requiring instead a mix of two or more populations with distinct enrichment histories.Comment: 18 pages, 17 figures. Accepted for publication in Ap

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Mathematics Attainment Falls Behind Reading in the Early Primary School Years

Early mathematics and reading are foundational skills for later academic and life outcomes. Despite their equal value to society, previous research finds reading skills exceeded those of mathematics in the first two years of primary school in the UK. The current study conducted a conceptual replication and extension of this finding using large-scale, longitudinal data from the Millennium Cohort Study. Within the same group of nearly 12,000 children, results showed at age 2-4 years, symbolic knowledge, which underpins mathematical development was stronger than alphabetic knowledge, a key component of reading development. However, following the introduction of formal schooling, reading attainment exceeded that of mathematics at 6-8 years. These findings have important implications for educational policy and practice, which currently places a greater focus on reading development, compared to mathematics. Directions for future research to enhance the scientific understanding of mathematical development that translates to effective mathematical interventions are discussed

Age of first digital device use and screen media use at age 15:A cross-sectional analysis of 384,591 participants from 55 countries

Objectives: We investigated the associations between age of first digital device use and screen media use at age 15. Study design and methods: Utilizing cross-sectional data from the 2018 Program for International Student Assessment, we analyzed responses from 384,591 fifteen-year-olds (50 % girls) from 55 countries on their age of first device use and current frequency of 12 screen behaviours. Behaviors were categorized as social, gaming, recreational, educational/practical (grouped into regular [every day; almost every day] and non-regular users [once or twice a week; once or twice a month; never or hardly ever]. Generalized linear regression, adjusted for highest level of schooling of mother/father and with student sampling and replicate weights to account for the sampling design was used to estimate prevalence ratios (PR) for regular use of each screen activity per additional year of age when first using devices. Results: Higher age of first device use was associated with lower prevalence of being a regular user for nine screen behaviours at age 15, with some sex differences. The strongest association was found for using email’ (PR per increasing year of first device use for total sample: 0.956 [95%CI 0.935; 0.977]; boys: 0.956 [95%CI 0.928; 0.986]) and playing collaborative online games (girls: 0.947 [95%CI 0.905; 0.991]). Later first use of devices was associated with decreased prevalence of regular use for social purposes at age 15. Conclusion: The later children start using digital devices, the less likely they are to be regular users at 15 years, especially social use. Delaying children's introduction to digital devices may decrease future use.</p

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer