Modelling height in adolescence: a comparison of methods for estimating the age at peak height velocity

Background: Controlling for maturational status and timing is crucial in lifecourse epidemiology. One popular non-invasive measure of maturity is the age at peak height velocity (PHV). There are several ways to estimate age at PHV, but it is unclear which of these to use in practice. Aim: To find the optimal approach for estimating age at PHV. Subjects and methods: Methods included the Preece & Baines non-linear growth model, multi-level models with fractional polynomials, SuperImposition by Translation And Rotation (SITAR) and functional data analysis. These were compared through a simulation study and using data from a large cohort of adolescent boys from the Christ’s Hospital School. Results: The SITAR model gave close to unbiased estimates of age at PHV, but convergence issues arose when measurement error was large. Preece & Baines achieved close to unbiased estimates, but shares similarity with the data generation model for our simulation study and was also computationally inefficient, taking 24 hours to fit the data from Christ’s Hospital School. Functional data analysis consistently converged, but had higher mean bias than SITAR. Almost all methods demonstrated strong correlations (r > 0.9) between true and estimated age at PHV. Conclusions: Both SITAR or the PBGM are useful models for adolescent growth and provide unbiased estimates of age at peak height velocity. Care should be taken as substantial bias and variance can occur with large measurement error

Direct observation of DNA threading in flap endonuclease complexes

Maintenance of genome integrity requires that branched nucleic acid molecules are accurately processed to produce double-helical DNA. Flap endonucleases are essential enzymes that trim such branched molecules generated by Okazaki fragment synthesis during replication. Here, we report crystal structures of bacteriophage T5 flap endonuclease in complexes with intact DNA substrates, and products, at resolutions of 1.9–2.2 Å. They reveal single-stranded DNA threading through a hole in the enzyme enclosed by an inverted Vshaped helical arch straddling the active site. Residues lining the hole induce an unusual barb-like conformation in the DNA substrate juxtaposing the scissile phosphate and essential catalytic metal ions. A series of complexes and biochemical analyses show how the substrate’s single-stranded branch approaches, threads through, and finally emerges on the far side of the enzyme. Our studies suggest that substrate recognition involves an unusual “flycasting, thread, bend and barb” mechanis

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Dacron® vs. PTFE as bypass materials in peripheral vascular surgery – systematic review and meta-analysis

Roll S, Müller-Nordhorn J, Keil T, et al. Dacron® vs. PTFE as bypass materials in peripheral vascular surgery – systematic review and meta-analysis. BMC Surgery. 2008;8(1): 22.Background: In peripheral vascular bypass surgery different synthetic materials are available for bypass grafting. It is unclear which of the two commonly used materials, polytetrafluoroethylene (PTFE) or polyester (Dacron®) grafts, is to be preferred. Thus, the aim of this meta-analysis and systematic review was to compare the effectiveness of these two prosthetic bypass materials (Dacron® and PTFE). Methods: We performed a systematic literature search in MEDLINE, Cochrane-Library – CENTRAL, EMBASE and other databases for relevant publications in English and German published between 1999 and 2008. Only randomized controlled trials were considered for inclusion. We assessed the methodological quality by means of standardized checklists. Primary patency was used as the main endpoint. Random-effect meta-analysis as well as pooling data in life table format was performed to combine study results. Results: Nine randomized controlled trials (RCT) were included. Two trials showed statistically significant differences in primary patency, one favouring Dacron® and one favouring PTFE grafts, while 7 trials did not show statistically significant differences between the two materials. Meta-analysis on the comparison of PTFE vs. Dacron® grafts yielded no differences with regard to primary patency rates (hazard ratio 1.04 (95% confidence interval [0.85;1.28]), no significant heterogeneity (p = 0.32, I2 = 14%)). Similarly, there were no significant differences with regard to secondary patency rates. Conclusion: Systematic evaluation and meta-analysis of randomized controlled trials comparing Dacron® and PTFE as bypass materials for peripheral vascular surgery showed no evidence of an advantage of one synthetic material over the other

A pilot survey of post-deployment health care needs in small community-based primary care clinics

<p>Abstract</p> <p>Background</p> <p>Relatively little is known regarding to what extent community-based primary care physicians are encountering post-deployment health care needs among veterans of the Afghanistan or Iraq conflicts and their family members.</p> <p>Methods</p> <p>This pilot study conducted a cross-sectional survey of 37 primary care physicians working at small urban and suburban clinics belonging to a practice-based research network in the south central region of Texas.</p> <p>Results</p> <p>Approximately 80% of the responding physicians reported caring for patients who have been deployed to the Afghanistan or Iraq war zones, or had a family member deployed. Although these physicians noted a variety of conditions related to physical trauma, mental illnesses and psychosocial disruptions such as marital, family, financial, and legal problems appeared to be even more prevalent among their previously deployed patients and were also noted among family members of deployed veterans.</p> <p>Conclusions</p> <p>Community-based primary care physicians should be aware of common post-deployment health conditions and the resources that are available to meet these needs.</p

XMPP for cloud computing in bioinformatics supporting discovery and invocation of asynchronous web services

Background: Life sciences make heavily use of the web for both data provision and analysis. However, the increasing amount of available data and the diversity of analysis tools call for machine accessible interfaces in order to be effective. HTTP-based Web service technologies, like the Simple Object Access Protocol (SOAP) and REpresentational State Transfer (REST) services, are today the most common technologies for this in bioinformatics. However, these methods have severe drawbacks, including lack of discoverability, and the inability for services to send status notifications. Several complementary workarounds have been proposed, but the results are ad-hoc solutions of varying quality that can be difficult to use. Results: We present a novel approach based on the open standard Extensible Messaging and Presence Protocol (XMPP), consisting of an extension (IO Data) to comprise discovery, asynchronous invocation, and definition of data types in the service. That XMPP cloud services are capable of asynchronous communication implies that clients do not have to poll repetitively for status, but the service sends the results back to the client upon completion. Implementations for Bioclipse and Taverna are presented, as are various XMPP cloud services in bio- and cheminformatics. Conclusion: XMPP with its extensions is a powerful protocol for cloud services that demonstrate several advantages over traditional HTTP-based Web services: 1) services are discoverable without the need of an external registry, 2) asynchronous invocation eliminates the need for ad-hoc solutions like polling, and 3) input and output types defined in the service allows for generation of clients on the fly without the need of an external semantics description. The many advantages over existing technologies make XMPP a highly interesting candidate for next generation online services in bioinformatics

Multisensory visual–tactile object related network in humans: insights gained using a novel crossmodal adaptation approach

Neuroimaging techniques have provided ample evidence for multisensory integration in humans. However, it is not clear whether this integration occurs at the neuronal level or whether it reflects areal convergence without such integration. To examine this issue as regards visuo-tactile object integration we used the repetition suppression effect, also known as the fMRI-based adaptation paradigm (fMR-A). Under some assumptions, fMR-A can tag specific neuronal populations within an area and investigate their characteristics. This technique has been used extensively in unisensory studies. Here we applied it for the first time to study multisensory integration and identified a network of occipital (LOtv and calcarine sulcus), parietal (aIPS), and prefrontal (precentral sulcus and the insula) areas all showing a clear crossmodal repetition suppression effect. These results provide a crucial first insight into the neuronal basis of visuo-haptic integration of objects in humans and highlight the power of using fMR-A to study multisensory integration using non-invasinve neuroimaging techniques

Discovering cancer genes by integrating network and functional properties

<p>Abstract</p> <p>Background</p> <p>Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI) data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO) annotations, to facilitate the identification of cancer genes.</p> <p>Methods</p> <p>Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1.</p> <p>Results</p> <p>Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs) with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1.</p> <p>Conclusion</p> <p>Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.</p

Assessing the Value of DNA Barcodes and Other Priority Gene Regions for Molecular Phylogenetics of Lepidoptera

BACKGROUND: Despite apparently abundant amounts of observable variation and species diversity, the order Lepidoptera exhibits a morphological homogeneity that has provided only a limited number of taxonomic characters and led to widespread use of nucleotides for inferring relationships. This study aims to characterize and develop methods to quantify the value of priority gene regions designated for Lepidoptera molecular systematics. In particular, I assess how the DNA barcode segment of the mitochondrial COI gene performs across a broad temporal range given its number one position of priority, most sequenced status, and the conflicting opinions on its phylogenetic performance. METHODOLOGY/PRINCIPAL FINDINGS: Gene regions commonly sequenced for lepidoptera phylogenetics were scored using multiple measures across three categories: practicality, which includes universality of primers and sequence quality; phylogenetic utility; and phylogenetic signal. I found that alternative measures within a category often appeared correlated, but high scores in one category did not necessarily translate into high scores in another. The DNA barcode was easier to sequence than other genes, and had high scores for utility but low signal above the genus level. CONCLUSIONS/SIGNIFICANCE: Given limited financial resources and time constraints, careful selection of gene regions for molecular phylogenetics is crucial to avoid wasted effort producing partially informative data. This study introduces an approach to assessing the value of gene regions prior to the initiation of new studies and presents empirical results to help guide future selections