Fast and accurate read mapping with approximate seeds and multiple backtracking

We present Masai, a read mapper representing the state-of-the-art in terms of speed and accuracy. Our tool is an order of magnitude faster than RazerS 3 and mrFAST, 2-4 times faster and more accurate than Bowtie 2 and BWA. The novelties of our read mapper are filtration with approximate seeds and a method for multiple backtracking. Approximate seeds, compared with exact seeds, increase filtration specificity while preserving sensitivity. Multiple backtracking amortizes the cost of searching a large set of seeds by taking advantage of the repetitiveness of next-generation sequencing data. Combined together, these two methods significantly speed up approximate search on genomic data sets. Masai is implemented in C++ using the SeqAn library. The source code is distributed under the BSD license and binaries for Linux, Mac OS X and Windows can be freely downloaded from http://www.seqan.de/projects/masai

Indices and Applications in High-Throughput Sequencing

Recent advances in sequencing technology allow to produce billions of base pairs per day in the form of reads of length 100 bp an longer and current developments promise the personal $1,000 genome in a couple of years. The analysis of these unprecedented amounts of data demands for efficient data structures and algorithms. One such data structures is the substring index, that represents all substrings or substrings up to a certain length contained in a given text. In this thesis we propose 3 substring indices, which we extend to be applicable to millions of sequences. We devise internal and external memory construction algorithms and a uniform framework for accessing the generalized suffix tree. Additionally we propose different index-based applications, e.g. exact and approximate pattern matching and different repeat search algorithms. Second, we present the read mapping tool RazerS, which aligns millions of single or paired-end reads of arbitrary lengths to their potential genomic origin using either Hamming or edit distance. Our tool can work either lossless or with a user-defined loss rate at higher speeds. Given the loss rate, we present a novel approach that guarantees not to lose more reads than specified. This enables the user to adapt to the problem at hand and provides a seamless tradeoff between sensitivity and running time. We compare RazerS with other state-of-the-art read mappers and show that it has the highest sensitivity and a comparable performance on various real-world datasets. At last, we propose a general approach for frequency based string mining, which has many applications, e.g. in contrast data mining. Our contribution is a novel and lightweight algorithm that is faster and uses less memory than the best available algorithms. We show its applicability for mining multiple databases with a variety of frequency constraints. As such, we use the notion of entropy from information theory to generalize the emerging substring mining problem to multiple databases. To demonstrate the improvement of our algorithm we compared to recent approaches on real-world experiments of various string domains, e.g. natural language, DNA, or protein sequences

RazerS 3: Faster, fully sensitive read mapping

Motivation: During the last years NGS sequencing has become a key technology for many applications in the biomedical sciences. Throughput continues to increase and new protocols provide longer reads than currently available. In almost all applications, read mapping is a first step. Hence, it is crucial to have algorithms and implementations that perform fast, with high sensitivity, and are able to deal with long reads and a large absolute number of indels. Results: RazerS is a read mapping program with adjustable sensitivity based on counting q-grams. In this work we propose the successor RazerS 3 which now supports shared-memory parallelism, an additional seed-based filter with adjustable sensitivity, a much faster, banded version of the Myers’ bit-vector algorithm for verification, memory saving measures and support for the SAM output format. This leads to a much improved performance for mapping reads, in particular long reads with many errors. We extensively compare RazerS 3 with other popular read mappers and show that its results are often superior to them in terms of sensitivity while exhibiting practical and often competetive run times. In addition, RazerS 3 works without a precomputed index. Availability and Implementation: Source code and binaries are freely available for download at http://www.seqan.de/projects/razers. RazerS 3 is implemented in C++ and OpenMP under a GPL license using the SeqAn library and supports Linux, Mac OS X, and Windows

Cultural Orientations of sport managers

Various interpretations of sport management are cultural constructs underpinned by core assumptions and values held by members of professional communities. Sport managers world wide share common problems, but differ in how they resolve them. These universal differences emerge from the relationships they form with other people, and their attitude to time, activities and the natural environment. This paper examines the role of sport managers’ cultural orientations in the interpretation and practice of sport management. Using a multiple dimension model (Hampden-Turner and Trompenaars, 2000) it sketches the cultural profiles of fifteen sport managers from seven countries. A combination of methods was employed including questionnaires, interviews and participant observation. It is contended that the culture of sport management concerns a social process by which managers get involved in reconciling seven fundamental cultural dilemmas in order to perform tasks and achieve certain ends. Thus, a knowledge of the cultural meaning of sport management in a particular country would equip sport managers with a valuable tool in managing both the cultural diversity of their own work forces and in developing appropriate cross-cultural skills needed for running international events, marketing campaigns, sponsorship deals and joint ventures

Noncardiac genetic predisposition in sudden infant death syndrome.

PURPOSE: Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls. METHODS: Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis. RESULTS: Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS. CONCLUSIONS: A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible

A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions

Background Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. Results Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. Conclusions Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively

Guidance on the Selection of Appropriate Indicators for Quantification of Antimicrobial Usage in Humans and Animals

An increasing variety of indicators of antimicrobial usage has become available in human and veterinary medicine, with no consensus on the most appropriate indicators to be used. The objective of this review is therefore to provide guidance on the selection of indicators, intended for those aiming to quantify antimicrobial usage based on sales, deliveries or reimbursement data. Depending on the study objective, different requirements apply to antimicrobial usage quantification in terms of resolution, comprehensiveness, stability over time, ability to assess exposure and comparability. If the aim is to monitor antimicrobial usage trends, it is crucial to use a robust quantification system that allows stability over time in terms of required data and provided output; to compare usage between different species or countries, comparability must be ensured between the different populations. If data are used for benchmarking, the system comprehensiveness is particularly crucial, while data collected to study the association between usage and resistance should express the exposure level and duration as a measurement of the exerted selection pressure. Antimicrobial usage is generally described as the number of technical units consumed normalized by the population at risk of being treated in a defined period. The technical units vary from number of packages to number of individuals treated daily by adding different levels of complexity such as daily dose or weight at treatment. These technical units are then related to a description of the population at risk, based either on biomass or number of individuals. Conventions and assumptions are needed for all of these calculation steps. However, there is a clear lack of standardization, resulting in poor transparency and comparability. By combining study requirements with available approaches to quantify antimicrobial usage, we provide suggestions on the most appropriate indicators and data sources to be used for a given study objective

Equipping for leadership: A Key mentoring practice

Previous studies examining predictors of mentoring benefits among pediatric staff nurse protegees representing healthcare organizations across 26 states demonstrated that protegee perception of quality was the single best predictor of mentoring benefits. The ability to identify the mentoring practices that predict specific benefits for individual nurses provides a better understanding of how mentoring relationships can be leveraged within health care organizations to promote the mutual benefits of mentoring. The primary aim of the study was to determine if mentoring practices predict mentoring benefits. In addition, the researchers were interested in exploring the relationship between the subscales of mentoring practices and benefits