Correlational Evidence between the Processing Speed Index, Coherent Motion Threshold, and Achievement Scores of Children With and Without Learning Disabilities

The purpose of this study was to determine the responses to three research questions. Is there an inverse relationship between PSI and CMT? Is a score on PSI associated with a child’s performance on math fluency and math calculation? Is CMT associated with PSI on math fluency and math calculation? Academic performance in math was measured by tests of math fluency and calculation. The study investigated the likelihood that a child with a slow PSI will have a high coherent motion threshold (CMT). The diagnostic status groups were comprised of 33 children from 2nd to 8th grades. The children were divided into three groups. One group of children with a learning disability in math only, one group of children with a learning disability in reading and in math, and one group of typically developing children. The group of typically developing subjects served as the control group, and the remaining two groups served as the experimental groups. A correlational research model was used to determine if a relationship exists between Coherent Motion and PSI. A linear regression analysis was conducted to test the correlation between CMT and PSI to gather data relative to the first research question. An Analysis of Variance (ANOVA) was conducted to further test Hypothesis One. Results indicated that there is a moderate negative relationship that exists between PSI and CMT. It was further hypothesized that PSI is associated with a child’s score on math fluency and math calculation, and that CMT is associated with PSI on math fluency and math calculation. A regression analysis was conducted to gather data relative to the second and third research question. Analysis of Variance (ANOVA) was conducted and the findings suggested a moderate negative relationship exist between CMT and PSI. A regression analysis of variance (ANOVA) was used to show the relationship between math fluency and PSI, math calculation and PSI, and math calculation along with math fluency and PSI. The results revealed that a strong direct relationship exists between math fluency, math calculation and processing speed. A regression model was created to determine if PSI and CMT, along with being identified as disabled, can be used as a predictor for math fluency and math calculation scores. When CMT is combined with PSI and students identified as having a disability, the findings revealed that it was not a strong predictor of math fluency and math calculation abilities

A Microscopic Model for D-Wave Pairing in the Cuprates: What Happens when Electrons Somersault?

We present a microscopic model for a strongly repulsive electron gas on a 2D square lattice. We suggest that nearest neighbor Coulomb repulsion stabilizes a state in which electrons undergo a "somersault" in their internal spin-space (spin-flux). When this spin-1/2 antiferromagnetic (AFM) insulator is doped, the charge carriers nucleate mobile, charged, bosonic vortex solitons accompanied by unoccupied states deep inside the Mott-Hubbard charge-transfer gap. This model provides a unified microscopic basis for (i) non-Fermi-liquid transport properties, (ii) mid-infrared optical absorption, (iii) destruction of AFM long range order with doping, (iv) angled resolved spectroscopy (ARPES), and (v) d-wave preformed charged carrier pairs. We use the Configuration Interaction (CI) method to study the quantum translational and rotational properties of such pairs. The CI method systematically describes fluctuation and quantum tunneling corrections to the Hartree-Fock approximation and recaptures essential features of the (Bethe ansatz) exact solution of the Hubbard model in 1D. For a single hole in the 2D AFM plane, we find a precursor to spin-charge separation. The CI ground state consists of a bound vortex-antivortex pair, one vortex carrying the charge and the other one carrying the spin of the doping hole.Comment: 10 pages, 8 figure

A microscopic model for d-wave charge carrier pairing and non-Fermi-liquid behavior in a purely repulsive 2D electron system

We investigate a microscopic model for strongly correlated electrons with both on-site and nearest neighbor Coulomb repulsion on a 2D square lattice. This exhibits a state in which electrons undergo a ``somersault'' in their internal spin-space (spin-flux) as they traverse a closed loop in external coordinate space. When this spin-1/2 antiferromagnetic (AFM) insulator is doped, the ground state is a liquid of charged, bosonic meron-vortices, which for topological reasons are created in vortex-antivortex pairs. The magnetic exchange energy of the distorted AFM background leads to a logarithmic vortex-antivortex attraction which overcomes the direct Coulomb repulsion between holes localized on the vortex cores. This leads to the appearance of pre-formed charged pairs. We use the Configuration Interaction (CI) Method to study the quantum translational and rotational motion of various charged magnetic solitons and soliton pairs. The CI method systematically describes fluctuation and quantum tunneling corrections to the Hartree-Fock Approximation (HFA). We find that the lowest energy charged meron-antimeron pairs exhibit d-wave rotational symmetry, consistent with the symmetry of the cuprate superconducting order parameter. For a single hole in the 2D AFM plane, we find a precursor to spin-charge separation in which a conventional charged spin-polaron dissociates into a singly charged meron-antimeron pair. This model provides a unified microscopic basis for (i) non-Fermi-liquid transport properties, (ii) d-wave preformed charged carrier pairs, (iii) mid-infrared optical absorption, (iv) destruction of AFM long range order with doping and other magnetic properties, and (v) certain aspects of angled resolved photo-emission spectroscopy (ARPES).Comment: 14 pages, 17 figure

EGR-2 Is Not Required for In Vivo CD4 T Cell Mediated Immune Responses

Background: The zinc finger transcription factor EGR-2 has been shown to play an important role in the induction of T cell anergy and the regulation of peripheral T cell tolerance. In vitro, a prior study has show that T cells deficient in EGR-2 are hyperproliferative to IL-2 and produce elevated levels of the effector cytokine IFN-c. EGR-2 deficient mice have increased levels of CD44 high T cells in peripheral lymphoid organs, and with age, develop autoimmune-like features. Principal Findings: Here we show that despite increased numbers of cells bearing an activated CD44 high CD62L low phenotype, T cells from young healthy EGR-2 deficient mice have normal proliferative and cytokine responses, and the mice themselves mount normal immune responses against minor histocompatibility antigens, and the pathogens Toxoplasma gondii and lymphocytic choriomeningitis virus. Conclusions: Our results indicate that EGR-2 is not required to mount normal acute in vivo immune responses against foreign antigens, and suggest instead that it may serve to regulate the response to chronic antigenic exposure, such as tha

Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials

Background Whether statin therapy is as effective in women as in men is debated, especially for primary prevention. We undertook a meta-analysis of statin trials in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare the effects of statin therapy between women and men. Methods We performed meta-analyses on data from 22 trials of statin therapy versus control (n=134 537) and five trials of more-intensive versus less-intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1·0 mmol/L reduction in LDL cholesterol and effects in men and women compared with a Cox model that adjusted for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance for the multiplicity of comparisons. Findings 46 675 (27%) of 174 149 randomly assigned participants were women. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1·1 mmol/L in statin vs control trials and roughly 0·5 mmol/L for more-intensive vs less-intensive therapy). Women were generally at lower cardiovascular risk than were men in these trials. The proportional reductions per 1·0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio [RR] 0·84, 99% CI 0·78–0·91) and men (RR 0·78, 99% CI 0·75–0·81, adjusted p value for heterogeneity by sex=0·33) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk (adjusted heterogeneity p=0·11). Likewise, the proportional reductions in major coronary events, coronary revascularisation, and stroke did not differ significantly by sex. No adverse effect on rates of cancer incidence or non-cardiovascular mortality was noted for either sex. These net benefits translated into all-cause mortality reductions with statin therapy for both women (RR 0·91, 99% CI 0·84–0·99) and men (RR 0·90, 99% CI 0·86–0·95; adjusted heterogeneity p=0·43). Interpretation In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events.UK Medical Research Council, British Heart Foundation, Australian National Health and Medical Research Council, European Community Biomed Program

Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

Background: Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages. Methods: In this meta-analysis, randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years. We analysed individual participant data from 22 trials (n=134 537) and detailed summary data from one trial (n=12 705) of statin therapy versus control, plus individual participant data from five trials of more intensive versus less intensive statin therapy (n=39 612). We subdivided participants into six age groups (55 years or younger, 56–60 years, 61–65 years, 66–70 years, 71–75 years, and older than 75 years). We estimated effects on major vascular events (ie, major coronary events, strokes, and coronary revascularisations), cause-specific mortality, and cancer incidence as the rate ratio (RR) per 1·0 mmol/L reduction in LDL cholesterol. We compared proportional risk reductions in different age subgroups by use of standard χ2 tests for heterogeneity when there were two groups, or trend when there were more than two groups. Findings: 14 483 (8%) of 186 854 participants in the 28 trials were older than 75 years at randomisation, and the median follow-up duration was 4·9 years. Overall, statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77–0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol. We observed a significant reduction in major vascular events in all age groups. Although proportional reductions in major vascular events diminished slightly with age, this trend was not statistically significant (ptrend=0·06). Overall, statin or more intensive therapy yielded a 24% (RR 0·76, 95% CI 0·73–0·79) proportional reduction in major coronary events per 1·0 mmol/L reduction in LDL cholesterol, and with increasing age, we observed a trend towards smaller proportional risk reductions in major coronary events (ptrend=0·009). We observed a 25% (RR 0·75, 95% CI 0·73–0·78) proportional reduction in the risk of coronary revascularisation procedures with statin therapy or a more intensive statin regimen per 1·0 mmol/L lower LDL cholesterol, which did not differ significantly across age groups (ptrend=0·6). Similarly, the proportional reductions in stroke of any type (RR 0·84, 95% CI 0·80–0·89) did not differ significantly across age groups (ptrend=0·7). After exclusion of four trials which enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (ptrend=0·01), and remained non-significant for major vascular events (ptrend=0·3). The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85–0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence. Interpretation: Statin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials. Funding: Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation

Bio-informatics analysis of a gene co-expression module in adipose tissue containing the diet-responsive gene Nnat

Background: Obesity causes insulin resistance in target tissues - skeletal muscle, adipose tissue, liver and the brain. Insulin resistance predisposes to type-2 diabetes (T2D) and cardiovascular disease (CVD). Adipose tissue inflammation is an essential characteristic of obesity and insulin resistance. Neuronatin (Nnat) expression has been found to be altered in a number of conditions related to inflammatory or metabolic disturbance, but its physiological roles and regulatory mechanisms in adipose tissue, brain, pancreatic islets and other tissues are not understood. Results: We identified transcription factor binding sites (TFBS) conserved in the Nnat promoter, and transcription factors (TF) abundantly expressed in adipose tissue. These include transcription factors concerned with the control of: adipogenesis (Ppar gamma, Klf15, Irf1, Creb1, Egr2, Gata3); lipogenesis (Mlxipl, Srebp1c); inflammation (Jun, Stat3); insulin signalling and diabetes susceptibility (Foxo1, Tcf7l2). We also identified NeuroD1 the only documented TF that controls Nnat expression. We identified KEGG pathways significantly associated with Nnat expression, including positive correlations with inflammation and negative correlations with metabolic pathways (most prominently oxidative phosphorylation, glycolysis and gluconeogenesis, pyruvate metabolism) and protein turnover. 27 genes, including; Gstt1 and Sod3, concerned with oxidative stress; Sncg and Cxcl9 concerned with inflammation; Ebf1, Lgals12 and Fzd4 involved in adipogenesis; whose expression co-varies with Nnat were identified, and conserved transcription factor binding sites identified on their promoters. Functional networks relating to each of these genes were identified. Conclusions: Our analysis shows that Nnat is an acute diet-responsive gene in white adipose tissue and hypothalamus; it may play an important role in metabolism, adipogenesis, and resolution of oxidative stress and inflammation in response to dietary exces

Statins Enhance Clonal Growth of Late Outgrowth Endothelial Progenitors and Increase Myocardial Capillary Density in the Chronically Ischemic Heart

Coronary artery disease and ischemic heart disease are leading causes of heart failure and death. Reduced blood flow to heart tissue leads to decreased heart function and symptoms of heart failure. Therapies to improve heart function in chronic coronary artery disease are important to identify. HMG-CoA reductase inhibitors (statins) are an important therapy for prevention of coronary artery disease, but also have non-cholesterol lowering effects. Our prior work showed that pravastatin improves contractile function in the chronically ischemic heart in pigs. Endothelial progenitor cells are a potential source of new blood vessels in ischemic tissues. While statins are known to increase the number of early outgrowth endothelial progenitor cells, their effects on late outgrowth endothelial progenitor cells (LOEPCs) and capillary density in ischemic heart tissue are not known. We hypothesized that statins exert positive effects on the mobilization and growth of late outgrowth EPCs, and capillary density in ischemic heart tissue.We determined the effects of statins on the mobilization and growth of late outgrowth endothelial progenitor cells from pigs. We also determined the density of capillaries in myocardial tissue in pigs with chronic myocardial ischemia with or without treatment with pravastatin. Pravastatin therapy resulted in greater than two-fold increase in CD31+ LOEPCs versus untreated animals. Addition of pravastatin or simvastatin to blood mononuclear cells increased the number of LOEPCs greater than three fold in culture. Finally, in animals with chronic myocardial ischemia, pravastatin increased capillary density 46%.Statins promote the derivation, mobilization, and clonal growth of LOEPCs. Pravastatin therapy in vivo increases myocardial capillary density in chronically ischemic myocardium, providing an in vivo correlate for the effects of statins on LOEPC growth in vitro. Our findings provide evidence that statin therapy can increase the density of capillaries in the chronically ischemic heart