Strengthening the Campus Leadership Team through Effective Principal and Counselor Relationships: Implications for Training

Campuses with successful leadership teams have a better opportunity to meet the ever-increasing and complex needs of the students they serve (Crowther, Kaagan, Ferguson, & Hann, 2002). These successful campuses are strengthened when they include strong principals and counseling teams with shared mutual trust and understanding that permeates the school climate (DeVoss & Andrews, 2006). A review of the literature revealed a paucity of studies examining the nature of successful principal-counselor relations and the impact of this relationship on student success, effective campus leadership teams, and an effective school climate that promotes learning. Meaningful dialogue and discussion of this critical professional relationship also were found lacking in the major counseling and educational leadership professional journals

Huntington’s disease age at motor onset is modified by the tandem hexamer repeat in TCERG1

Huntington’s disease is caused by an expanded CAG tract in HTT. The length of the CAG tract accounts for over half the variance in age at onset of disease, and is influenced by other genetic factors, mostly implicating the DNA maintenance machinery. We examined a single nucleotide variant, rs79727797, on chromosome 5 in the TCERG1 gene, previously reported to be associated with Huntington’s disease and a quasi-tandem repeat (QTR) hexamer in exon 4 of TCERG1 with a central pure repeat. We developed a method for calling perfect and imperfect repeats from exome-sequencing data, and tested association between the QTR in TCERG1 and residual age at motor onset (after correcting for the effects of CAG length in the HTT gene) in 610 individuals with Huntington’s disease via regression analysis. We found a significant association between age at onset and the sum of the repeat lengths from both alleles of the QTR (p = 2.1 × 10−9), with each added repeat hexamer reducing age at onset by one year (95% confidence interval [0.7, 1.4]). This association explained that previously observed with rs79727797. The association with age at onset in the genome-wide association study is due to a QTR hexamer in TCERG1, translated to a glutamine/alanine tract in the protein. We could not distinguish whether this was due to cis-effects of the hexamer repeat on gene expression or of the encoded glutamine/alanine tract in the protein. These results motivate further study of the mechanisms by which TCERG1 modifies onset of HD

Reproducibility of adenosine stress cardiovascular magnetic resonance in multi-vessel symptomatic coronary artery disease

<p>Abstract</p> <p>Purpose</p> <p>First-pass perfusion cardiovascular magnetic resonance (CMR) is increasingly being utilized in both clinical practice and research. However, the reproducibility of this technique remains incompletely evaluated, particularly in patients with severe coronary artery disease (CAD). The purpose of this study was to determine the inter-study reproducibility of adenosine stress CMR in patients with symptomatic multi-vessel CAD and those at low risk for CAD.</p> <p>Methods</p> <p>Twenty patients (10 with CAD, 10 low risk CAD) underwent two CMR scans 8 ± 2 days apart. Basal, mid and apical left ventricular short axis slices were acquired using gadolinium 0.05 mmol/kg at peak stress (adenosine, 140 μ/kg/min, 4 min) and rest. Myocardial perfusion was evaluated qualitatively by assessing the number of ischemic segments, and semi-quantitatively by determining the myocardial perfusion reserve index (MPRi) using a normalized upslope method. Inter-study and observer reproducibility were assessed--the latter being defined by the coefficient of variation (CoV), which was calculated from the standard deviation of the differences of the measurements, divided by the mean. Additionally, the percentage of myocardial segments with perfect agreement and inter- and intra-observer MPRi correlation between studies, were also determined.</p> <p>Results</p> <p>The CoV for the number of ischemic segments was 31% with a mean difference of -0.15 ± 0.88 segments and 91% perfect agreement between studies. MPRi was lower in patients with CAD (1.13 ± 0.21) compared to those with low risk CAD (1.59 ± 0.58), p = 0.02. The reproducibility of MPRi was 19% with no significant difference between patients with CAD and those with low risk CAD (p = 0.850). Observer reproducibility for MPRi was high: inter-observer CoV 9%, r = 0.93 and intra-observer CoV 5%, r = 0.94. For trials using perfusion CMR as an endpoint, an estimated sample size of 12 subjects would be required to detect a two-segment change in the number of ischemic segments (power 0.9, α 0.05).</p> <p>Conclusions</p> <p>Adenosine stress CMR, by qualitative and semi-quantitative normalized upslope analyses are reproducible techniques in both patients with multi-vessel CAD and those without known CAD. The robust inter-study reproducibility of perfusion CMR supports its clinical and research application.</p

Pulsed Doppler assessment of left ventricular diastolic filling in children with left ventricular outflow obstruction before and after balloon angioplasty

To assess left ventricular (LV) diastolic filling in children with pressure overload hypertrophy, 12 patients with LV outflow obstruction (7 with aortic valve stenosis and 5 with aortic coarctation) and 12 healthy, age-matched control subjects were examined. Each child underwent M-mode echocardiography and pulsed Doppler examination of the LV inflow. The patients with LV outflow obstruction had cardiac catheterization and balloon angioplasty. Their echo/Doppler examinations were performed in the catheterization laboratory before and immediately after balloon angioplasty. From the M-mode echocardiogram, the LV cavity dimensions and wall thicknesses, LV mass and shortening fraction were measured. The following measurements were made from the Doppler recording: peak velocities at rapid ventricular filling (peak E) and during atrial contraction (peak A), ratio of peak E to peak A velocities, total area under the Doppler curve, percent of the total Doppler area occurring in the first one-third of diastole (0.33 area fraction), percent of the total area occurring under the E wave (E area fraction), percent of the total area occurring under the A wave (A area fraction) and the ratio of E area to A area.Before balloon angioplasty, the patients with LV outflow obstruction had higher peak E velocity (1.06 +/- 0.18 vs 0.88 +/- 0.11 m/s, p &lt; 0.01), higher peak A velocity (0.86 +/- 0.22 vs 0.47 +/- 0.08 m/s, p &lt; 0.01) and lower E/A velocity ratio (1.29 +/- 0.27 vs 1.93 +/- 0.34, p &lt; 0.01) than the normal subjects. In the patient group, 0.33 area fraction was significantly lower (0.38 +/- 0.07 vs 0.57 +/- 0.09, p &lt; 0.01) and A area fraction was significantly higher (0.44 +/- 0.14 vs 0.23 +/- 0.07, p &lt; 0.01) than in the normal subjects. Also, patients with LV outflow obstruction had greater LV wall thickness, smaller LV cavity dimensions and greater LV mass compared with normal subjects. In patients before and after balloon angioplasty, there was a significant decrease in LV outflow gradient (64 +/- 23 vs 33 +/- 22 mm Hg, p &lt; 0.01), but there was no change in any echo/Doppler measurement. Thus, children with LV outflow obstruction have abnormal LV early diastolic relaxation with a shift in filling toward late diastole. Immediately after successful relief of the systolic pressure overload, diastolic filling patterns are unchanged, suggesting that hypertrophy rather than afterload mismatch is the primary determinant of the impaired relaxation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28087/1/0000533.pd

Identification of Genetic Factors that Modify Clinical Onset of Huntington’s Disease

SummaryAs a Mendelian neurodegenerative disorder, the genetic risk of Huntington’s disease (HD) is conferred entirely by an HTT CAG repeat expansion whose length is the primary determinant of the rate of pathogenesis leading to disease onset. To investigate the pathogenic process that precedes disease, we used genome-wide association (GWA) analysis to identify loci harboring genetic variations that alter the age at neurological onset of HD. A chromosome 15 locus displays two independent effects that accelerate or delay onset by 6.1 years and 1.4 years, respectively, whereas a chromosome 8 locus hastens onset by 1.6 years. Association at MLH1 and pathway analysis of the full GWA results support a role for DNA handling and repair mechanisms in altering the course of HD. Our findings demonstrate that HD disease modification in humans occurs in nature and offer a genetic route to identifying in-human validated therapeutic targets in this and other Mendelian disorders.PaperCli

Serum autoantibody measurement for the detection of hepatocellular carcinoma

Background: Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC.Methods: Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA.Results: Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel.Conclusions: This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung)

Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST)

PURPOSE: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS: A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI (v CT) or three scans (v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS: Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (-3.5 to -0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION: Surveillance is a safe management approach-advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule

Implementing efficient concerted rotations using Mathematica and C code

In this article we demonstrate a general and efficient metaprogramming implementation of concerted rotations using Mathematica. Concerted rotations allow the movement of a fixed portion of a polymer backbone with fixed bending angles, like a protein, while maintaining the correct geometry of the backbone and the initial and final points of the portion fixed. Our implementation uses Mathematica to generate a C code which is then wrapped in a library by a Python script. The user can modify the Mathematica notebook to generate a set of concerted rotations suited for a particular backbone geometry, without having to write the C code himself. The resulting code is highly optimized, performing on the order of thousands of operations per second