A comparison of internal validation techniques for multifactor dimensionality reduction

<p>Abstract</p> <p>Background</p> <p>It is hypothesized that common, complex diseases may be due to complex interactions between genetic and environmental factors, which are difficult to detect in high-dimensional data using traditional statistical approaches. Multifactor Dimensionality Reduction (MDR) is the most commonly used data-mining method to detect epistatic interactions. In all data-mining methods, it is important to consider internal validation procedures to obtain prediction estimates to prevent model over-fitting and reduce potential false positive findings. Currently, MDR utilizes cross-validation for internal validation. In this study, we incorporate the use of a three-way split (3WS) of the data in combination with a post-hoc pruning procedure as an alternative to cross-validation for internal model validation to reduce computation time without impairing performance. We compare the power to detect true disease causing loci using MDR with both 5- and 10-fold cross-validation to MDR with 3WS for a range of single-locus and epistatic disease models. Additionally, we analyze a dataset in HIV immunogenetics to demonstrate the results of the two strategies on real data.</p> <p>Results</p> <p>MDR with 3WS is computationally approximately five times faster than 5-fold cross-validation. The power to find the exact true disease loci without detecting false positive loci is higher with 5-fold cross-validation than with 3WS before pruning. However, the power to find the true disease causing loci in addition to false positive loci is equivalent to the 3WS. With the incorporation of a pruning procedure after the 3WS, the power of the 3WS approach to detect only the exact disease loci is equivalent to that of MDR with cross-validation. In the real data application, the cross-validation and 3WS analyses indicate the same two-locus model.</p> <p>Conclusions</p> <p>Our results reveal that the performance of the two internal validation methods is equivalent with the use of pruning procedures. The specific pruning procedure should be chosen understanding the trade-off between identifying all relevant genetic effects but including false positives and missing important genetic factors. This implies 3WS may be a powerful and computationally efficient approach to screen for epistatic effects, and could be used to identify candidate interactions in large-scale genetic studies.</p

PinR mediates the generation of reversible population diversity in Streptococcus zooepidemicus

Opportunistic pathogens must adapt to and survive in a wide range of complex ecosystems. Streptococcus zooepidemicus is an opportunistic pathogen of horses and many other animals, including humans. The assembly of different surface architecture phenotypes from one genotype is likely to be crucial to the successful exploitation of such an opportunistic lifestyle. Construction of a series of mutants revealed that a serine recombinase, PinR, inverts 114 bp of the promoter of SZO_08560, which is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats. Inversion acts as a switch, controlling the transcription of this sortase-processed protein, which may enhance the attachment of S. zooepidemicus to equine trachea. The genome of a recently sequenced strain of S. zooepidemicus, 2329 (Sz2329), was found to contain a disruptive internal inversion of 7 kb of the FimIV pilus locus, which is bordered by TAGAAA and TTTCTA inverted repeats. This strain lacks pinR and this inversion may have become irreversible following the loss of this recombinase. Active inversion of FimIV was detected in three strains of S. zooepidemicus, 1770 (Sz1770), B260863 (SzB260863) and H050840501 (SzH050840501), all of which encoded pinR. A deletion mutant of Sz1770 that lacked pinR was no longer capable of inverting its internal region of FimIV. The data highlight redundancy in the PinR sequence recognition motif around a short TAGA consensus and suggest that PinR can reversibly influence the wider surface architecture of S. zooepidemicus, providing this organism with a bet-hedging solution to survival in fluctuating environments

Implementing evidence-informed policy into practice for health care professionals managing people with low back pain in Australian rural settings: A preliminary prospective single-cohort study

Objective: To provide access to professional development opportunities for health care professionals, especially in rural Australian regions, consistent with recommendations in the Australian National Pain Strategy and state government policy. Design and Setting: A preliminary prospective, single-cohort study design, which aligned health policy with evidence-informed clinical practice, evaluated the implementation and effectiveness of an interprofessional, health care provider pain education program (hPEP) for management of nonspecific low back pain (nsLBP) in rural Western Australia. Intervention: The 6.5-hour hPEP intervention was delivered to 60 care providers (caseload nsLBP 19.8% ± 22.5) at four rural WA regions. Outcome Measures: Outcomes were recorded at baseline and 2 months post-intervention regarding attitudes, beliefs (modified Health Care Providers Pain and Impairment Relationship Scale [HC-PAIRS]), Back Pain Beliefs Questionnaire [BBQ]), and self-reported evidence-based clinical practice (knowledge and skills regarding nsLBP, rated on a 5-point Likert scale with 1 = nil and 5 = excellent).Results: hPEP was feasible to implement. At 2 months post-hPEP, responders' (response rate 53%) improved evidence-based beliefs were indicated by HC-PAIRS scores: baseline mean (SD) [43.2 (9.3)]; mean difference (95% CI) [−5.9 (−8.6 to −3.1)]; and BBQ baseline [34.3 (6.8)]; mean difference [2.1 (0.5 to 3.6)]. Positive shifts were observed for all measures of clinical knowledge and skills (P < 0.001) and increased assistance with planning lifestyle changes (P < 0.001), advice on self-management (P = 0.010), and for decreased referrals for spinal imaging (P = 0.03). Conclusions: This policy-into-practice educational program is feasible to implement in rural Western Australia (WA). While preliminary data are encouraging, a further randomized controlled trial is recommended

Estimating spring terminus submarine melt rates at a greenlandic tidewater glacier using satellite imagery

Oceanic forcing of the Greenland Ice Sheet is believed to promote widespread thinning at tidewater glaciers, with submarine melting proposed as a potential trigger of increased glacier calving, retreat, and subsequent acceleration. The precise mechanism(s) driving glacier instability, however, remain poorly understood, and while increasing evidence points to the importance of submarine melting, estimates of melt rates are uncertain. Here we estimate submarine melt rate by examining freeboard changes in the seasonal ice tongue of Kangiata Nunaata Sermia (KNS) at the head of Kangersuneq Fjord (KF), southwest Greenland. We calculate melt rates for March and May 2013 by differencing along-fjord surface elevation, derived from high-resolution TanDEM-X digital elevation models (DEMs), in combination with ice velocities derived from offset tracking applied to TerraSAR-X imagery. Estimated steady state melt rates reach up to 1.4 ± 0.5m d-1 near the glacier grounding line, with mean values of up to 0.8 ± 0.3 and 0.7 ± 0.3m d-1 for the eastern and western parts of the ice tongue, respectively. Melt rates decrease with distance from the ice front and vary across the fjord. This methodology reveals spatio-temporal variations in submarine melt rates (SMRs) at tidewater glaciers which develop floating termini, and can be used to improve our understanding of ice-ocean interactions and submarine melting in glacial fjords.Publisher PDFPeer reviewe

Rosetta-Alice Observations of Exospheric Hydrogen and Oxygen on Mars

The European Space Agency's Rosetta spacecraft, en route to a 2014 encounter with comet 67P/Churyumov-Gerasimenko, made a gravity assist swing-by of Mars on 25 February 2007, closest approach being at 01:54UT. The Alice instrument on board Rosetta, a lightweight far-ultraviolet imaging spectrograph optimized for in situ cometary spectroscopy in the 750-2000 A spectral band, was used to study the daytime Mars upper atmosphere including emissions from exospheric hydrogen and oxygen. Offset pointing, obtained five hours before closest approach, enabled us to detect and map the HI Lyman-alpha and Lyman-beta emissions from exospheric hydrogen out beyond 30,000 km from the planet's center. These data are fit with a Chamberlain exospheric model from which we derive the hydrogen density at the 200 km exobase and the H escape flux. The results are comparable to those found from the the Ultraviolet Spectrometer experiment on the Mariner 6 and 7 fly-bys of Mars in 1969. Atomic oxygen emission at 1304 A is detected at altitudes of 400 to 1000 km above the limb during limb scans shortly after closest approach. However, the derived oxygen scale height is not consistent with recent models of oxygen escape based on the production of suprathermal oxygen atoms by the dissociative recombination of O2+.Comment: 17 pages, 8 figures, accepted for publication in Icaru

Ultraviolet Spectroscopy of Comet 9P/Tempel 1 with Alice/Rosetta during the Deep Impact Encounter

We report on spectroscopic observations of periodic comet 9P/Tempel 1 by the Alice ultraviolet spectrograph on the Rosetta spacecraft in conjunction with NASA's Deep Impact mission. Our objectives were to measure an increase in atomic and molecular emissions produced by the excavation of volatile sub-surface material. We unambiguously detected atomic oxygen emission from the quiescent coma but no enhancement at the 10% (1-sigma) level following the impact. We derive a quiescent water production rate of 9 x 10^27 molecules per second with an estimated uncertainty of 30%. Our upper limits to the volatiles produced by the impact are consistent with other estimates.Comment: 11 pages, 4 postscript figures. Accepted for publication in Icarus special issue on Deep Impac