NMR identification of calcineurin B residues affected by binding of a calcineurin A peptide

AbstractTriple resonance 3D NMR methods have been used to study the interaction between calcineurin B and a peptide fragment of calcineurin A for which it has high affinity (KD ∼4 × 10−7 M). Although calcineurin B aggregates at NMR concentrations of ∼ 1 mM, in the presence of a target peptide fragment of calcineurin A it becomes monomeric and yields NMR spectra that are very similar to those reported previously for calcineurin B solubilized by the zwitterionic detergent CHAPS. Changes in chemical shifts between CHAPS- and peptide-solubilized calcineurin B are small which is indicative of no differences in secondary structure. Residues most affected by binding to target peptide are found primarily on the hydrophobic faces of the four helices, present in each of the two globular domains in calcineurin B, and in the loops connecting helices II and III, IV and V, and possibly in the C-terminal 12 residues, which also exhibit a change in mobility

An invitation to grieve: reconsidering critical incident responses by support teams in the school setting

This paper proposes that consideration could be given to an invitational intervention rather than an expectational intervention when support personnel respond to a critical incident in schools. Intuitively many practitioners know that it is necessary for guidance/counselling personnel to intervene in schools in and following times of trauma. Most educational authorities in Australia have mandated the formulation of a critical incident intervention plan. This paper defines the term critical incident and then outlines current intervention processes, discussing the efficacy of debriefing interventions. Recent literature suggests that even though it is accepted that a planned intervention is necessary, there is scant evidence as to the effectiveness of debriefing interventions in stemming later symptoms of post traumatic stress disorder. The authors of this paper advocate for an expressive therapy intervention that is invitational rather than expectational, arguing that not all people respond to trauma in the same way and to expect that they will need to recall and retell what has happened is most likely a dangerous assumption. A model of invitation using Howard Gardner’s (1983) multiple intelligences is proposed so that students are invited to grieve and understand emotionally what is happening to them following a critical incident

Development and validation of MIX: comprehensive free software for meta-analysis of causal research data

BACKGROUND: Meta-analysis has become a well-known method for synthesis of quantitative data from previously conducted research in applied health sciences. So far, meta-analysis has been particularly useful in evaluating and comparing therapies and in assessing causes of disease. Consequently, the number of software packages that can perform meta-analysis has increased over the years. Unfortunately, it can take a substantial amount of time to get acquainted with some of these programs and most contain little or no interactive educational material. We set out to create and validate an easy-to-use and comprehensive meta-analysis package that would be simple enough programming-wise to remain available as a free download. We specifically aimed at students and researchers who are new to meta-analysis, with important parts of the development oriented towards creating internal interactive tutoring tools and designing features that would facilitate usage of the software as a companion to existing books on meta-analysis. RESULTS: We took an unconventional approach and created a program that uses Excel as a calculation and programming platform. The main programming language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for Applications in Excel 2000 and higher. The development took approximately two years and resulted in the 'MIX' program, which can be downloaded from the program's website free of charge. Next, we set out to validate the MIX output with two major software packages as reference standards, namely STATA (metan, metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta-analyses that had been published in major journals were used as data sources. All numerical and graphical results from analyses with MIX were identical to their counterparts in STATA and CMA. The MIX program distinguishes itself from most other programs by the extensive graphical output, the click-and-go (Excel) interface, and the educational features. CONCLUSION: The MIX program is a valid tool for performing meta-analysis and may be particularly useful in educational environments. It can be downloaded free of charge via or

Inappropriate Implantable Cardioverter-Defibrillator Shocks Incidence, Predictors, and Impact on Mortality

ObjectivesThe purpose of this study was to assess the incidence, predictors, and outcome of inappropriate shocks in implantable cardioverter-defibrillator (ICD) patients.BackgroundDespite the benefits of ICD therapy, inappropriate defibrillator shocks continue to be a significant drawback. The prognostic importance of inappropriate shocks outside the setting of a clinical trial remains unclear.MethodsFrom 1996 to 2006, all recipients of defibrillator devices equipped with intracardiac electrogram storage were included in the current analysis and clinically assessed at implantation. During follow-up, the occurrence of inappropriate ICD shocks and all-cause mortality was noted.ResultsA total of 1,544 ICD patients (79% male, age 61 ± 13 years) were included in the analysis. During the follow-up period of 41 ± 18 months, 13% experienced ≥1 inappropriate shocks. The cumulative incidence steadily increased to 18% at 5-year follow-up. Independent predictors of the occurrence of inappropriate shocks included a history of atrial fibrillation (hazard ratio [HR]: 2.0, p < 0.01) and age younger than 70 years (HR: 1.8, p = 0.01). Experiencing a single inappropriate shock resulted in an increased risk of all-cause mortality (HR: 1.6, p = 0.01). Mortality risk increased with every subsequent shock, up to an HR of 3.7 after 5 inappropriate shocks.ConclusionsIn a large cohort of ICD patients, inappropriate shocks were common. The most important finding is the association between inappropriate shocks and mortality, independent of interim appropriate shocks

Growth or decline in the Church of England during the decade of Evangelism: did the Churchmanship of the Bishop matter?

The Decade of Evangelism occupied the attention of the Church of England throughout the 1990s. The present study employs the statistics routinely published by the Church of England in order to assess two matters: the extent to which these statistics suggest that the 43 individual dioceses finished the decade in a stronger or weaker position than they had entered it and the extent to which, according to these statistics, the performance of dioceses led by bishops shaped in the Evangelical tradition differed from the performance of dioceses led by bishops shaped in the Catholic tradition. The data demonstrated that the majority of dioceses were performing less effectively at the end of the decade than at the beginning, in terms of a range of membership statistics, and that the rate of decline varied considerably from one diocese to another. The only exception to the trend was provided by the diocese of London, which experienced some growth. The data also demonstrated that little depended on the churchmanship of the diocesan bishop in shaping diocesan outcomes on the performance indicators employed in the study