The introduction of a surgical safety checklist in a tertiary referral obstetric centre

Background: Surgery-related adverse events remain a significant and often under-reported problem. In a recent study, the introduction of a perioperative checklist by the WHO reduced deaths and complications by 46% and 36% respectively. The authors wished to evaluate the introduction of a surgical safety checklist in a busy obstetric tertiary referral centre by assessing staff attitudes, checklist compliance and effects upon patients. Methods: A questionnaire-based assessment was performed on staff working in obstetric theatres before and after the introduction of the surgical safety checklist. Checklist compliance was assessed at 3 months and 1 year. Patients were asked questions relating to the performance of the surgical safety checklist in order to evaluate any anxiety caused. Results: Non-medical staff were significantly more likely than medical staff to feel familiar with other team members both before (p<0.001) and after (

Paper Session III: Research Brief: A Curriculum for Teaching Information Technology Investigative Techniques for Auditors

Recent prosecutions of highly publicized white-collar crimes combined with public outrage have resulted in heightened regulation and greater emphasis on systems of internal control. Because both white-collar and cybercrimes are usually perpetrated through computers, auditors’ knowledge of information technology (IT) is now more vital than ever. However, preserving digital evidence and investigative techniques, which can be essential to fraud examinations, are not skills frequently taught in accounting programs. Furthermore, many students are not instructed in the use of computer assisted auditing tools and techniques – applications that might uncover fraudulent activity. Only a limited number of university-level accounting classes provide instruction in IT investigative techniques

Two p53 tetramers bind one consensus DNA response element

p53 tumor suppressor is a transcription factor that controls cell cycle and genetic integrity. In response to genotoxic stress p53 activates DNA repair, cell cycle arrest, apoptosis or senescence, which are initiated via p53 binding to its specific DNA response elements (RE). The consensus p53 DNA RE consists of two decameric palindromic half-site sequences. Crystallographic studies have demonstrated that two isolated p53 DNA-binding core domains interact with one half-site of the p53 DNA REs suggesting that one p53 tetramer is bound to one RE. However, our recent 3D cryo-EM studies showed that the full-length p53 tetramer is bound to only one half-site of RE. Here, we have used biochemical and electron microscopy (EM) methods to analyze DNA-binding of human and murine p53 tetramers to various p53 DNA REs. Our new results demonstrate that two p53 tetramers can interact sequence-specifically with one DNA RE at the same time. In particular, the EM structural analysis revealed that two p53 tetramers bind one DNA RE simultaneously with DNA positioned between them. These results demonstrate a mode different from that assumed previously for the p53-DNA interaction and suggest important biological implications on p53 activity as a transcriptional regulator of cellular response to stress

Progenitors for the corneal endothelium and trabecular meshwork: a potential source for personalized stem cell therapy in corneal endothelial diseases and glaucoma

Several adult stem cell types have been found in different parts of the eye, including the corneal epithelium, conjunctiva, and retina. In addition to these, there have been accumulating evidence that some stem-like cells reside in the transition area between the peripheral corneal endothelium (CE) and the anterior nonfiltering portion of the trabecular meshwork (TM), which is known as the Schwalbe's Ring region. These stem/progenitor cells may supply new cells for the CE and TM. In fact, the CE and TM share certain similarities in terms of their embryonic origin and proliferative capacity in vivo. In this paper, we discuss the putative stem cell source which has the potential for replacement of lost and nonfunctional cells in CE diseases and glaucoma. The future development of personalized stem cell therapies for the CE and TM may reduce the requirement of corneal grafts and surgical treatments in glaucoma.published_or_final_versio

Abstract Learning Frameworks for Synthesis

We develop abstract learning frameworks (ALFs) for synthesis that embody the principles of CEGIS (counter-example based inductive synthesis) strategies that have become widely applicable in recent years. Our framework defines a general abstract framework of iterative learning, based on a hypothesis space that captures the synthesized objects, a sample space that forms the space on which induction is performed, and a concept space that abstractly defines the semantics of the learning process. We show that a variety of synthesis algorithms in current literature can be embedded in this general framework. While studying these embeddings, we also generalize some of the synthesis problems these instances are of, resulting in new ways of looking at synthesis problems using learning. We also investigate convergence issues for the general framework, and exhibit three recipes for convergence in finite time. The first two recipes generalize current techniques for convergence used by existing synthesis engines. The third technique is a more involved technique of which we know of no existing instantiation, and we instantiate it to concrete synthesis problems

Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens

BACKGROUND: Natural antibodies directed at carbohydrates reject porcine xenografts. They are initially expressed in germline configuration and are encoded by a small number of structurally-related germline progenitors. The transplantation of genetically-modified pig organs prevents hyperacute rejection, but delayed graft rejection still occurs, partly due to humoral responses. IgV(H )genes encoding induced xenoantibodies are predominantly, not exclusively, derived from germline progenitors in the V(H)3 family. We have previously identified the immunoglobulin heavy chain genes encoding V(H)3 xenoantibodies in patients and primates. In this manuscript, we complete the structural analysis of induced xenoantibodies by identifying the IgV(H )genes encoding the small proportion of V(H)4 xenoantibodies and the germline progenitors encoding xenoantibody light chains. This information has been used to define the xenoantibody/carbohydrate binding site using computer-simulated modeling. RESULTS: The VH4-59 gene encodes antibodies in the V(H)4 family that are induced in human patients mounting active xenoantibody responses. The light chain of xenoantibodies is encoded by DPK5 and HSIGKV134. The structural information obtained by sequencing analysis was used to create computer-simulated models. Key contact sites for xenoantibody/carbohydrate interaction for V(H)3 family xenoantibodies include amino acids in sites 31, 33, 50, 57, 58 and the CDR3 region of the IgV(H )gene. Site-directed mutagenesis indicates that mutations in predicted contact sites alter binding to carbohydrate xenoantigens. Computer-simulated modeling suggests that the CDR3 region directly influences binding. CONCLUSION: Xenoantibodies induced during early and delayed xenograft responses are predominantly encoded by genes in the V(H)3 family, with a small proportion encoded by V(H)4 germline progenitors. This restricted group can be identified by the unique canonical structure of the light chain, heavy chain and CDR3. Computer-simulated models depict this structure with accuracy, as confirmed by site-directed mutagenesis. Computer-simulated drug design using computer-simulated models may now be applied to develop new drugs that may enhance the survival of xenografted organs

Montelukast in the treatment of duodenal eosinophilia in children with dyspepsia: Effect on eosinophil density and activation in relation to pharmacokinetics

<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated the clinical efficacy of montelukast in a randomized double-blind controlled cross-over trial in patients with dyspepsia in association with duodenal eosinophilia. The mechanism of this clinical response is unknown but could involve a decrease in eosinophil density or activation.</p> <p>Methods</p> <p>Twenty-four dyspeptic patients 8–17 years of age underwent initial blood sampling and endoscopy with biopsy. Eighteen of these patients had elevated duodenal eosinophil density and underwent repeat blood sampling and endoscopy following 21 days of therapy with montelukast (10 mg/day). The following were determined: global clinical response on a 5-point Lickert-type scale, eosinophil density utilizing H & E staining, eosinophil activation determined by degranulation indices on electron microscopy, and serum cytokine concentrations. On day 21, pharmacokinetics and duodenal mucosal drug concentrations were determined.</p> <p>Results</p> <p>Eighty-three percent of the patients had a positive clinical response to montelukast with regard to relief of pain with 50% having a complete or nearly complete clinical response. The response was unrelated to systemic drug exposure or to mucosal drug concentration. Other than a mild decrease in eosinophil density in the second portion of the duodenum, there were no significant changes in eosinophil density, eosinophil activation, or serum cytokine concentrations following treatment with montelukast. Pre-treatment TNF-α concentration was negatively correlated with clinical response.</p> <p>Conclusion</p> <p>The short-term clinical response to montelukast does not appear to result from changes in eosinophil density or activation. Whether the effect is mediated through specific mediators or non-inflammatory cells such as enteric nerves remains to be determined.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov; NCT00148603</p