Comparative Effectiveness of Elementary School Achievement In English Speaking Countries

The general problem of this study was to determine the relative effectiveness or general progress of instruction of school children in English speaking countries of the world as compared with the progress in certain Kansas schools. Teachers and headmasters in the foreign countries were careful to mention the fact that many processes of learning are different in their country than it is in the United States. Such spelling words as program (programme), center (centre), and labor (labour) could not be used, and problems dealing in dollars and cents were not used

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters.

Funder: All funders per study are acknowledged in the Supplementary FileA new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Lack of Renoprotective Effect of Chronic Intravenous Angiotensin-(1-7) or Angiotensin-(2-10) in a Rat Model of Focal Segmental Glomerulosclerosis

<div><p>Unopposed angiotensin (Ang) II-mediated cellular effects may lead to progressive glomerulosclerosis. While Ang-II can be locally generated in the kidneys, we previously showed that glomerular podocytes primarily convert Ang-I, the precursor of Ang-II, to Ang-(1-7) and Ang-(2-10), peptides that have been independently implicated in biological actions opposing those of Ang-II. Therefore, we hypothesized that Ang-(1-7) and Ang-(2-10) could be renoprotective in the fawn-hooded hypertensive rat, a model of focal segmental glomerulosclerosis. We evaluated the ability of 8–12 week-long intravenous administration of either Ang-(1-7) or Ang-(2-10) (100–400 ng/kg/min) to reduce glomerular injury in uni-nephrectomized fawn-hooded hypertensive rats, early or late in the disease. Vehicle-treated rats developed hypertension and lesions of focal segmental glomerulosclerosis. No reduction in glomerular damage was observed, as measured by either 24-hour urinary protein excretion or histological examination of glomerulosclerosis, upon Ang-(1-7) or Ang-(2-10) administration, regardless of peptide dose or disease stage. On the contrary, when given at 400 ng/kg/min, both peptides induced a further increase in systolic blood pressure. Content of Ang peptides was measured by parallel reaction monitoring in kidneys harvested at sacrifice. Exogenous administration of Ang-(1-7) and Ang-(2-10) did not lead to a significant increase in their corresponding intrarenal levels. However, the relative abundance of Ang-(1-7) with respect to Ang-II was increased in kidney homogenates of Ang-(1-7)-treated rats. We conclude that chronic intravenous administration of Ang-(1-7) or Ang-(2-10) does not ameliorate glomerular damage in a rat model of focal segmental glomerulosclerosis and may induce a further rise in blood pressure, potentially aggravating glomerular injury.</p></div

Ratios of intrarenal Ang peptide abundance.

<p>Kidneys were harvested at the end of the late disease protocol (after 12 weeks of therapy). Treatment arms are listed in the <i>x</i>-axes. Group specific <i>post-hoc</i> pairwise differences (P<0.05) are indicated by letters. Equivalent letters indicate groups that are not significantly different from each other and different letters indicate a significant difference was detected between groups. ANOVA (p<0.05) indicates if differences between groups were detected, but no pairwise differences were significant; n = 5/group Data are in means ± SEM. L = low-dose, H = high-dose.</p

Experimental protocols.

<p>Schematic of treatment protocols employed to test the effect of early (Panel <i>A</i>) or late (Panel <i>B</i>) chronic intravenous administration of Ang-(1-7) and Ang-(2-10) on the progression of glomerulosclerosis in uni-nephrectomized FHH rats.</p

Effect of Ang peptides on blood pressure.

<p>Tail-cuff systolic blood pressure readings in uni-nephrectomized FHH rats obtained in <i>A</i>: <i>early disease protocol [n = 4/group, except captopril group (n = 5)]:</i> at the time of uni-nephrectomy (week 6), initial mini-pump implantation (week 7), mini-pump exchange (week 11), and sacrifice (week 15); or <i>B</i>: <i>late disease protocol [n = 9/group, except vehicle group (n = 7)]:</i> at the time of uni-nephrectomy (week 6), initial mini-pump implantation (week 18), mini-pump exchange (week 24), and sacrifice (week 30). * = significantly lower than vehicle (p = 0.014); ¥ = significantly higher than vehicle (p<0.001). Only 2 rats from the Ang-(2-10) HD group and none of the Ang-II group were alive at week 30. Data are in means ± SEM. SBP = systolic blood pressure, LD = low-dose, HD = high-dose.</p

LC/MS/MS peptide transition ions, optimized collision energy and standard curve correlation coefficients.

<p>On column limit of detection (LOD), On column lower limit of quantification (LLOQ) and concentration range measured for peptides in this study. ∧ indicates ¹³C/¹⁵N SIS peptide. CV = coefficient of variation.</p><p>LC/MS/MS peptide transition ions, optimized collision energy and standard curve correlation coefficients.</p

Intrarenal Ang peptide content as measured by Parallel Reaction Monitoring.

<p>Kidneys were harvested at the end of the late disease protocol (after 12 weeks of therapy). Treatment arms are listed in the <i>x</i>-axes. ANOVA (p<0.05) indicates differences between groups that were detected, but no pairwise differences were significant; n = 5/group Data are in means ± SEM. L = low-dose, H = high-dose.</p