ALBERT

Description: The two-dimensional scattering of water waves over a finite region of arbitrarily varying topography linking two semi-infinite regions of constant depth is considered. Unlike many approaches to this problem, the formulation employed is exact in the context of linear theory, utilizing simple combinations of Green's functions appropriate to water of constant depth and the Cauchy-Riemann equations to derive a system of coupled integral equations for components of the fluid velocity at certain locations. Two cases arise, depending on whether the deepest point of the topography does or does not lie below the lower of the semi-infinite horizontal bed sections. In each, the reflected and transmitted wave amplitudes are related to the incoming wave amplitudes by a scattering matrix which is defined in terms of inner products involving the solution of the corresponding integral equation system. This solution is approximated by using the variational method in conjunction with a judicious choice of trial function which correctly models the fluid behaviour at the free surface and near the joins of the varying topography with the constant-depth sections, which may not be smooth. The numerical results are remarkably accurate, with just a two-term trial function giving three decimal places of accuracy in the reflection and transmission coefficients in most cases, whilst increasing the number of terms in the trial function results in rapid convergence. The method is applied to a range of examples.

Description: The behaviour of water waves over periodic beds is considered in a two-dimensional context and using linear theory. Three cases are investigated: the scattering of waves by a finite section of periodic topography; the Bloch problem for infinite periodic topography; and sloshing motions over periodic topography confined between vertical boundaries. Connections are established between these problems. A transfer matrix method incorporating evanescent modes is developed for the scattering problem, which reduces the computation to that required for a single period, without compromising full linear theory. The problem of the existence of Bloch waves can also be posed on a single period, leading to a close relationship between it and the scattering problem. Sloshing motions over periodic beds, which may be regarded as special cases of the Bloch problem, are also found to have a significant connection with wave scattering. Integral equations methods allied to the Galerkin approximation are used to resolve the three problems numerically. In particular, the full linear solution for Bragg resonance is presented, allowing the accuracy of existing approximations to this phenomenon to be assessed. The selection of results given illustrates the main features of the work.

Description: An investigation is carried out into the effect on wave propagation of an ice sheet of varying thickness floating on water of varying depth, in three dimensions. By deriving a variational principle equivalent to the governing equations of linear theory and invoking the mild-slope approximation in respect of the ice thickness and water depth variations, a simplified form of the problem is obtained from which the vertical coordinate is absent. Two situations are considered: the scattering of flexural-gravity waves by variations in the thickness of an infinite ice sheet and by depth variations; and the scattering of free-surface gravity waves by an ice sheet of finite extent and varying thickness, again incorporating arbitrary topography. Numerical methods are devised for the two-dimensional versions of these problems and a selection of results is presented. The variational approach that is developed can be used to implement more sophisticated approximations and is capable of producing the solution of full linear problems by taking a large enough basis in the Rayleigh-Ritz method. It is also applicable to other situations that involve wave scattering by a floating elastic sheet. © 2004 Cambridge University Press.

Description: The scattering and trapping of water waves by three-dimensional submerged topography, infinite and periodic in one horizontal coordinate and of finite extent in the other, is considered under the assumptions of linearized theory. The mild-slope approximation is used to reduce the governing boundary value problem to one involving a form of the Helmholtz equation in which the coefficient depends on the topography and is therefore spatially varying. Two problems are considered: The scattering by the topography of parallel-crested obliquely incident waves and the propagation of trapping modes along the periodic topography. Both problems are formulated in terms of 'domain' integral equations which are solved numerically. Trapped waves are found to exist over any periodic topography which is 'sufficiently' elevated above the unperturbed bed level. In particular, every periodic topography wholly elevated above that level supports trapped waves. Fundamental differences are shown to exist between these trapped waves and the analogous Rayleigh-Bloch waves which exist on periodic gratings in acoustic theory. Results computed for the scattering problem show that, remarkably, there exist zeros of transmission at discrete wavenumbers for any periodic bed elevation and for all incident wave angles. One implication of this property is that total reflection of an incident wave of a particular frequency will occur in a channel with a single symmetric elevation on the bed. The zeros of transmission in the scattering problem are shown to be related to the presence of a 'nearly trapped' mode in the corresponding homogeneous problem. The scattering of waves by multiple rows of periodic topography is also considered and it is shown how Bragg resonance - well-established in scattering of waves by two-dimensional ripple beds - occurs in modes other than the input mode.

Description: Background: While efforts to improve cancer outcomes have typically focused on improving quality of care, recently, a growing emphasis has been placed on timely access to quality cancer care. This retrospective cohort study examines, at a population level, the relationship between quality and timeliness of colorectal cancer (CRC) care in a single Canadian province (Nova Scotia). Through the provincial cancer registry, we identified all residents diagnosed with invasive CRC between 2001 and 2005 that underwent a non-emergent resection. Using anonymized administrative databases that are individually linked at the patient level, we obtained clinicodemographic, diagnostic, and treatment event data. Selected charts were reviewed to ensure completeness of chemotherapy data.Performance on six quality indicators and the percentage of patients achieving wait time benchmarks for diagnosis, surgery, and adjuvant therapy were calculated. The relationship between quality indicators and wait time intervals was examined using logistic regression. Results: Where an association was identified, patients who received 'higher quality care' had longer wait times. Individuals who received a complete preoperative colonoscopy were less likely to meet benchmarks for time from presentation to diagnosis and from diagnosis to surgery. Those who received an appropriate radiation oncology consultation were less likely to meet benchmarks for time from diagnosis to surgery and from surgery to adjuvant therapy. Conclusions: As governments and other organizations move forward with strategies to reduce wait times, they must also focus on how to define and monitor quality care, and consider the relationship between these two dimensions of health care. Similarly, when developing quality improvement initiatives, the impact on resource utilization and potential to create longer waits for care must be considered.

Description: Background: Most PCR-based diagnostics are still considered time- and labor-intensive due to disparate purification, amplification, and detection steps. Advancements in PCR enzymes and buffer chemistry have increased inhibitor tolerance, facilitating PCR directly from crude samples. Obviating the need for DNA purification, while lacking a concentration step, these direct sample methods are particularly apt for human genetic testing. However, direct PCR protocols have traditionally employed thermal cyclers with slow ramp rates and conservative hold times that significantly increase an assay?s time-to-result. For this proof-of-principle study, our objective was to significantly reduce sample preparation and assay time for a PCR-based genetic test, for myotonic dystrophy type 1 (DM1), by pairing an inhibitor-resistant enzyme mix with a rapid thermal cycler to analyze samples directly in whole blood. Methods: DM1 genetic screening was done with an adapted conventional PCR approach that employed the Streck Philisa? Thermal Cycler, the inhibitor-resistant NEBNext? High-Fidelity 2X PCR Master Mix, and agarose gel electrophoresis or an Agilent 2100 Bioanalyzer for detection. The Gene Link? Myotonic Dystrophy Genemer? Kit was used as a reference assay kit to evaluate the rapid assay. Results: In this work, a rapid and direct PCR assay testing 10% whole blood as template has been developed as an exclusionary screening assay for DM1, a triple-repeat genetic disorder. PCR amplification was completed in 15 minutes using 30 cycles, including in situ hot-start/cell lysis. Out of the 40 donors screened, this assay identified 23 (57.5%) as DM1 negative suggesting no need for further testing. These data are 100% concordant with data collected using the commercially available Gene Link Genemer? Kit per the kit-specific PCR protocol. Conclusions: The PCR assay described in this study amplified DM1 short tandem repeats in 15 minutes. By eliminating sample purification and slower conventional PCR protocols, we demonstrated how adaptation of current PCR technology and chemistries can produce a simple-to-use exclusionary screening assay that is independent of up-front sample prep, improving a clinical lab technician?s time-to-result. We envision this direct and rapid methodology could be applied to other conventional PCR-based genetic tests and sample matrices where genomic DNA is targeted for analysis within a given molecular diagnostic platform.

Description: Background: The pig is a biomedical model to study human and livestock traits. Many of these traits are controlled by neuropeptides that result from the cleavage of prohormones by prohormone convertases. Only 45 prohormones have been confirmed in the pig. Sequence homology can be ineffective to annotate prohormone genes in sequenced species like the pig due to the multifactorial nature of the prohormone processing. The goal of this study is to undertake the first complete survey of prohormone and prohormone convertases genes in the pig genome. These genes were functionally annotated based on 35 gene expression microarray experiments. The cleavage sites of prohormone sequences into potentially active neuropeptides were predicted. Results: We identified 95 unique prohormone genes, 2 alternative calcitonin-related sequences, 8 prohormone convertases and 1 cleavage facilitator in the pig genome 10.2 assembly and trace archives. Of these, 11 pig prohormone genes have not been reported in the UniProt, UniGene or Gene databases. These genes are intermedin, cortistatin, insulin-like 5, orexigenic neuropeptide QRFP, prokineticin 2, prolactin-releasing peptide, parathyroid hormone 2, urocortin, urocortin 2, urocortin 3, and urotensin 2-related peptide. In addition, a novel neuropeptide S was identified in the pig genome correcting the previously reported pig sequence that is identical to the rabbit sequence. Most differentially expressed prohormone genes were under-expressed in pigs experiencing immune challenge relative to the un-challenged controls, in non-pregnant relative to pregnant sows, in old relative to young embryos, and in non-neural relative to neural tissues. The cleavage prediction based on human sequences had the best performance with a correct classification rate of cleaved and non-cleaved sites of 92% suggesting that the processing of prohormones in pigs is similar to humans. The cleavage prediction models did not find conclusive evidence supporting the production of the bioactive neuropeptides urocortin 2, urocortin 3, torsin family 2 member A, tachykinin 4, islet amyloid polypeptide, and calcitonin receptor-stimulating peptide 2 in the pig. Conclusions: The present genomic and functional characterization supports the use of the pig as an effective animal model to gain a deeper understanding of prohormones, prohormone convertases and neuropeptides in biomedical and agricultural research.

Description: Motivation: Reliable estimation of the mean fragment length for next-generation short-read sequencing data is an important step in next-generation sequencing analysis pipelines, most notably because of its impact on the accuracy of the enriched regions identified by peak-calling algorithms. Although many peak-calling algorithms include a fragment-length estimation subroutine, the problem has not been adequately solved, as demonstrated by the variability of the estimates returned by different algorithms. Results: In this article, we investigate the use of strand cross-correlation to estimate mean fragment length of single-end data and show that traditional estimation approaches have mixed reliability. We observe that the mappability of different parts of the genome can introduce an artificial bias into cross-correlation computations, resulting in incorrect fragment-length estimates. We propose a new approach, called mappability-sensitive cross-correlation (MaSC), which removes this bias and allows for accurate and reliable fragment-length estimation. We analyze the computational complexity of this approach, and evaluate its performance on a test suite of NGS datasets, demonstrating its superiority to traditional cross-correlation analysis. Availability: An open-source Perl implementation of our approach is available at http://www.perkinslab.ca/Software.html . Contact: tperkins@ohri.ca Supplementary information: Supplementary data are available at Bioinformatics online.