Effects of ADHD on writing composition product and process in school-age students

Objective: This study examined the relationship between ADHD and writing performance. Method: Students in Grades 3 to 7, 84 with ADHD and 135 age and gender-matched controls completed a writing task (including process logs), and measures of, working memory and attention. Results: Students with ADHD wrote texts of similar length but with poorer structure, coherence and ideation. 6.7% of the variance in writing quality was explained by whether or not the student had an ADHD diagnosis, after control for IQ and age-within-year, with students with ADHD producing text that was less coherent, well structured, and ideationally rich and to spend less time thinking about and reviewing their text. Half of the effect on text quality could be attributed to working memory and sustained attention effects. Conclusions: ADHD has some effect on writing performance which can, in part, be explained by working memory and attentional deficits

Characterization of T-bet and eomes in peripheral human immune cells.

The T-box transcription factors T-bet and Eomesodermin (Eomes) have been well defined as key drivers of immune cell development and cytolytic function. While the majority of studies have defined the roles of these factors in the context of murine T-cells, recent results have revealed that T-bet, and possibly Eomes, are expressed in other immune cell subsets. To date, the expression patterns of these factors in subsets of human peripheral blood mononuclear cells beyond T-cells remain relatively uncharacterized. In this study, we used multiparametric flow cytometry to characterize T-bet and Eomes expression in major human blood cell subsets, including total CD4(+) and CD8(+) T-cells, γδ T-cells, invariant NKT cells, natural killer cells, B-cells, and dendritic cells. Our studies identified novel cell subsets that express T-bet and Eomes and raise implications for their possible functions in the context of other human immune cell subsets besides their well-known roles in T-cells. The corrigendum regards data and text for the final figure of the manuscript, Figure 7: Subsequent analysis of T-bet levels in human lymphocytes comparing different permeabilization procedures (eBioscience FoxP3 transcription factor kit, BD Pharmingen Cytofix/Cytoperm) has revealed variable findings in the level of T-bet expression detected within certain lymphocyte populations. While this does not change our conclusions for the majority of the populations assessed in this study, B cells in particular show differences under these conditions. Specifically, permeabilization via the eBioscience FoxP3 transcription factor staining buffer set indicates that subpopulations of memory B cells express significantly higher levels of T-bet (MFI) compared to plasmablasts, and that plasmablasts express T-bet only at low levels. Subsequent RNA transcript analysis confirms that plasmablasts express T-bet RNA at a level comparable to naïve B cells. Together, in combination with fluorescence-minus-one and isotype control studies, these new findings suggest that subsets memory B cells, not plasmablasts, express the highest levels of T-bet in the B cell compartment and plasmablasts express T-bet at a lower frequency than is reported in Figure 7. Figure 7 Legend should read: (C) Histograms depicting T-bet expression levels in B-cells and NK cells from a representative donor. Histograms represent the following subsets: naïve B-cells (thick black line), memory B-cells (shaded gray), plasmablasts (thin black line), CD56bright NK cells (gray line), and CD56dim NK cells (shaded black). B-cell results section should be titled T-bet is predominantly expressed in mature memory B-cells and should read: While Eomes was undetectable in B-cells (data not shown), we found T-bet in ~10% of B-cells (Figure 7B). This T-bet expression was largely relegated to memory B-cells, with significantly lower amounts observed in transitional/immature B-cells, naïve B-cells, and plasmablasts (Figure 7B). Greater than 15% of memory B-cells expressed T-bet, a significantly higher frequency than that of all other B-cell populations, suggesting that T-bet may play a particularly important role in memory B-cell function. The discussion related to T-bet expression in plasmablasts should be reconsidered as follows: We found that T-bet is not significantly expressed in transitional/immature B-cells, naïve B-cells, and plasmablasts, but is highly expressed in subsets of memory-B cells. Reduced frequencies of T-bet expression in plasmablasts indicate a specific role for T-bet at the memory B-cell stage of development, which may no longer be necessary after further differentiation to the plasmablast stage. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

Realistic Earth escape strategies for solar sailing

With growing interest in solar sailing comes the requirement to provide a basis for future detailed planetary escape mission analysis by drawing together prior work, clarifying and explaining previously anomalies. Previously unexplained seasonal variations in sail escape times from Earth orbit are explained analytically and corroborated within a numerical trajectory model. Blended-sail control algorithms, explicitly independent of time, which providenear-optimal escape trajectories and maintain a safe minimum altitude and which are suitable as a potential autonomous onboard controller, are then presented. These algorithms are investigated from a range of initial conditions and are shown to maintain the optimality previously demonstrated by the use of a single-energy gain control law but without the risk of planetary collision. Finally, it is shown that the minimum sail characteristic acceleration required for escape from a polar orbit without traversing the Earth shadow cone increases exponentially as initial altitude is decreased

Spin-1/2 J1-J2 model on the body-centered cubic lattice

Using exact diagonalization (ED) and linear spin wave theory (LSWT) we study the influence of frustration and quantum fluctuations on the magnetic ordering in the ground state of the spin-1/2 J1-J2 Heisenberg antiferromagnet (J1-J2 model) on the body-centered cubic (bcc) lattice. Contrary to the J1-J2 model on the square lattice, we find for the bcc lattice that frustration and quantum fluctuations do not lead to a quantum disordered phase for strong frustration. The results of both approaches (ED, LSWT) suggest a first order transition at J2/J1 $\approx$ 0.7 from the two-sublattice Neel phase at low J2 to a collinear phase at large J2.Comment: 6.1 pages 7 figure

How much dystrophin is enough: the physiological consequences of different levels of dystrophin in the mdx mouse

Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly understood. In order to robustly evaluate functional improvement, we used in situ protocols in the mdx mouse to measure muscle strength and resistance to eccentric contraction-induced damage. Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. We reveal that 15% homogeneous dystrophin expression is sufficient to protect against eccentric contraction-induced injury. In addition, we demonstrate a >40% increase in specific isometric force following repeated administrations. Strikingly, we show that changes in muscle strength are proportional to dystrophin expression levels. These data define the dystrophin restoration levels required to slow down or prevent disease progression and improve overall muscle function once a dystrophic environment has been established in the mdx mouse model

Evaluation of subcutaneous implantable cardioverter-defibrillator performance in patients with ion channelopathies from the EFFORTLESS cohort and comparison with a meta-analysis of transvenous ICD outcomes

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to conventional transvenous ICD (TV-ICD) therapy to reduce lead complications. Objective: To evaluate outcomes in channelopathy vs patients with structural heart disease in the EFFORTLESS-SICD Registry and with a previously reported TV-ICD meta-analysis in channnelopathies. Methods: The EFFORTLESS registry includes 199 patients with channelopathies (Brugada syndrome 83, long QT syndrome 24, idiopathic ventricular fibrillation 78, others 14) and 786 patients with structural heart disease. Results: Channelopathy patients were younger (39 ± 14 years vs 51 ± 17 years; P 200 beats per minute (P = .0002). Annualized appropriate shock, IAS, and complication rates appear to be lower for the S-ICD vs meta-analysis TV-ICD patients, particularly lead complications. Conclusion: EFFORTLESS demonstrates similar S-ICD efficacy and a nonsignificant, lower rate of IAS in channelopathy patients as compared to structural heart disease. Comparable IAS rates were achieved with the device programmed to higher rates for channelopathy patients

GPUVerify: A Verifier for GPU Kernels

We present a technique for verifying race- and divergence-freedom of GPU kernels that are written in mainstream ker-nel programming languages such as OpenCL and CUDA. Our approach is founded on a novel formal operational se-mantics for GPU programming termed synchronous, delayed visibility (SDV) semantics. The SDV semantics provides a precise definition of barrier divergence in GPU kernels and allows kernel verification to be reduced to analysis of a sequential program, thereby completely avoiding the need to reason about thread interleavings, and allowing existing modular techniques for program verification to be leveraged. We describe an efficient encoding for data race detection and propose a method for automatically inferring loop invari-ants required for verification. We have implemented these techniques as a practical verification tool, GPUVerify, which can be applied directly to OpenCL and CUDA source code. We evaluate GPUVerify with respect to a set of 163 kernels drawn from public and commercial sources. Our evaluation demonstrates that GPUVerify is capable of efficient, auto-matic verification of a large number of real-world kernels

Small-x QCD studies with CMS at the LHC

The capabilities of the CMS experiment to study the low-x parton structure and QCD evolution in the proton and the nucleus at LHC energies are presented through four different measurements, to be carried out in Pb-Pb at sqrt(s_NN) = 5.5 TeV: (i) the charged hadron rapidity density $dN_{ch}/d\eta$ and (ii) the ultraperipheral (photo)production of Upsilon; and in p-p at sqrt(s) = 14 TeV: (iii) inclusive forward jets and (iv) Mueller-Navelet dijets (separated by $Delta\eta\gtrsim$ 8).Comment: Quark Matter'06 Proceedings. To appear in J.Phys.

Cmah-dystrophin deficient mdx mice display an accelerated cardiac phenotype that is improved following peptide-PMO exon skipping treatment

Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin protein, leading to progressive muscle weakness and premature death due to respiratory and/or cardiac complications. Cardiac involvement is characterized by progressive dilated cardiomyopathy, decreased fractional shortening and metabolic dysfunction involving reduced metabolism of fatty acids—the major cardiac metabolic substrate. Several mouse models have been developed to study molecular and pathological consequences of dystrophin deficiency, but do not recapitulate all aspects of human disease pathology and exhibit a mild cardiac phenotype. Here we demonstrate that Cmah (cytidine monophosphate-sialic acid hydroxylase)-deficient mdx mice (Cmah−/−;mdx) have an accelerated cardiac phenotype compared to the established mdx model. Cmah−/−;mdx mice display earlier functional deterioration, specifically a reduction in right ventricle (RV) ejection fraction and stroke volume (SV) at 12 weeks of age and decreased left ventricle diastolic volume with subsequent reduced SV compared to mdx mice by 24 weeks. They further show earlier elevation of cardiac damage markers for fibrosis (Ctgf), oxidative damage (Nox4) and haemodynamic load (Nppa). Cardiac metabolic substrate requirement was assessed using hyperpolarized magnetic resonance spectroscopy indicating increased in vivo glycolytic flux in Cmah−/−;mdx mice. Early upregulation of mitochondrial genes (Ucp3 and Cpt1) and downregulation of key glycolytic genes (Pdk1, Pdk4, Ppara), also denote disturbed cardiac metabolism and shift towards glucose utilization in Cmah−/−;mdx mice. Moreover, we show long-term treatment with peptide-conjugated exon skipping antisense oligonucleotides (20-week regimen), resulted in 20% cardiac dystrophin protein restoration and significantly improved RV cardiac function. Therefore, Cmah−/−;mdx mice represent an appropriate model for evaluating cardiac benefit of novel DMD therapeutics