Multi-Site N-glycan mapping study 1: Capillary electrophoresis – laser induced fluorescence

An international team that included 20 independent laboratories from biopharmaceutical companies, universities, analytical contract laboratories and national authorities in the United States, Europe and Asia was formed to evaluate the reproducibility of sample preparation and analysis of N-glycans using capillary electrophoresis of 8-aminopyrene-1,3,6-trisulfonic acid (APTS)-labeled glycans with laser induced fluorescence (CE-LIF) detection (16 sites) and ultra highperformance liquid chromatography (UHPLC, 12 sites; results to be reported in a subsequent publication). All participants used the same lot of chemicals, samples, reagents, and columns/capillaries to run their assays. Migration time, peak area and peak area percent values were determined for all peaks with >0.1% peak area. Our results demonstrated low variability and high reproducibility, both, within any given site as well across all sites, which indicates that a standard N-glycan analysis platform appropriate for general use (clone selection, process development, lot release, etc.) within the industry can be established

Phylo: A Citizen Science Approach for Improving Multiple Sequence Alignment

BACKGROUND: Comparative genomics, or the study of the relationships of genome structure and function across different species, offers a powerful tool for studying evolution, annotating genomes, and understanding the causes of various genetic disorders. However, aligning multiple sequences of DNA, an essential intermediate step for most types of analyses, is a difficult computational task. In parallel, citizen science, an approach that takes advantage of the fact that the human brain is exquisitely tuned to solving specific types of problems, is becoming increasingly popular. There, instances of hard computational problems are dispatched to a crowd of non-expert human game players and solutions are sent back to a central server. METHODOLOGY/PRINCIPAL FINDINGS: We introduce Phylo, a human-based computing framework applying "crowd sourcing" techniques to solve the Multiple Sequence Alignment (MSA) problem. The key idea of Phylo is to convert the MSA problem into a casual game that can be played by ordinary web users with a minimal prior knowledge of the biological context. We applied this strategy to improve the alignment of the promoters of disease-related genes from up to 44 vertebrate species. Since the launch in November 2010, we received more than 350,000 solutions submitted from more than 12,000 registered users. Our results show that solutions submitted contributed to improving the accuracy of up to 70% of the alignment blocks considered. CONCLUSIONS/SIGNIFICANCE: We demonstrate that, combined with classical algorithms, crowd computing techniques can be successfully used to help improving the accuracy of MSA. More importantly, we show that an NP-hard computational problem can be embedded in casual game that can be easily played by people without significant scientific training. This suggests that citizen science approaches can be used to exploit the billions of "human-brain peta-flops" of computation that are spent every day playing games. Phylo is available at: http://phylo.cs.mcgill.ca

Optimal dosing of antibiotics in critically ill patients by using continuous/extended infusions: a systematic review and meta-analysis

Abstract Introduction The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials, such as extended/continuous infusions, in critically ill patients is associated with improved outcomes as compared with traditional dosing methods. Methods We searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions with traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed by using random-effects models. Results Of 1,319 citations, 13 randomized controlled trials (RCTs) (n=782 patients) and 13 cohort studies (n=2,117 patients) met the inclusion criteria. Compared with traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68; 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference, −1.5; 95% CI, −2.8 to −0.2 days, P=0.02), but not mortality (RR, 0.87; 95% CI, 0.64 to 1.19; P=0.38). No significant between-trial heterogeneity was found for these analyses (I 2 =0). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR, 0.83; 95% CI, 0.69 to 1.00; P=0.054). Conclusions Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to define better the utility of continuous/extended infusions in the era of antibiotic resistance

Object-oriented technology: from diagram to code with visual paradigm for UML (2nd ed.)

This book is written for students and developers who wish to master the essential skills and techniques in applying the Unified Modeling Language (UML) for software development. The reader will learn object-oriented analysis, design, and implementation using appropriate UML models, processes, techniques, and tools. Accompanying this book is the Community Edition of Visual Paradigm for UMP (VP-UML), an award-winning Computer-Aided Software Engineering (CASE) tool, which allows the reader to put the theories learned into practice immediately

Cervical arthroplasty with the Bryan disc

Cervical arthroplasty is a promising nonfusion alternative for the treatment of degenerative disc disease. After anterior cervical discectomy for neurological decompression, the intervertebral space is reconstructed by use of a metal and polymer prosthesis, allowing semiconstrained motion in multiple planes. This approach allows for preservation of cervical motion, potentially reducing the risk of transitional-level disease

Jejunal web masquerading as intestinal malrotation in a neonate with bilious vomiting: A case report

Neonatal bilious vomiting is considered as a pathological sign and warrant urgent medical attention. Upper gastro-intestinal contrast study can be notoriously difficult to diagnose incomplete intestinal rotation, especially when there is partial hold up of the contrast at the duodenum. We report a case of a full term neonate with incomplete jejunal obstruction due to a fenestrated jejunal web, presenting with bilious vomiting and masquerading as intestinal malrotation in the contrast study. We discuss the recent literature and the potential diagnostic difficulty in the diagnosis of jejunal web. In view of the low specificity of radiological imaging study of jejunal web, clinicians should be aware that congenital gastro-intestinal webs are a possible cause of partial gastro-intestinal obstruction in infants and children

Use of remote blood releasing system for red cell transfusion in hospice care center

Objectives: It is quite common to have advanced cancer or end-stage renal disease patients for regular or even frequent blood transfusion in palliative care. However, due to geographical reason in some hospice centers, blood transfusion is sometimes difficult if blood bank is closed during non-office hour or not available. Methods: Here, we reported a new blood releasing system, that is, remote blood releasing system, that could be used safely by nursing staff alone when the blood bank was closed during the night time and holiday. Results: On-call nursing staff could collect red cells successful in these two cases. Conclusion: The new blood releasing system seems useful. However, larger sample sizes and longer period of study are required to estimate its efficacy and safety. The provision of antibody-positive red cells and platelet remained a limitation of this system

Intra-vesical knot of bladder catheter in an extremely low birthweight neonate: A case report

Premature and extremely low birth weight (ELBW) neonates are at high risk of developing multiple co-morbidities and often require urinary catheterization for various medical indications. Intra-vesical knotting of bladder catheter is a known but uncommon complication of this procedure. We report a case of an ELBW baby boy with a knotted bladder catheter requiring surgical retrieval. After an elective operation for the closure of patent ductus arteriosus, a 4 French urinary catheter was inserted into an ELBW baby boy for urine output monitoring and left in-situ. Resistance was encountered in attempt to remove the urinary catheter. Abdominal X Ray confirmed intra-vesical knotting of the tube. Knot unravelling by interventional radiology was attempted but was unsuccessful. Open extra-peritoneal bladder exploration was performed for the retrieval of the tightly knotted catheter. A 6 French transurethral Foley catheter was inserted for bladder drainage. Upon removal of the Foley's catheter on day 5 post op, the baby was able to void spontaneously. With literature review, we postulated the potential risk factors resulting in this potentially avoidable iatrogenic unusual complication. Recommendations were suggested to avoid further incidences