A genome-wide survey of segmental duplications that mediate common human genetic variation of chromosomal architecture.

Recent studies have identified a small number of genomic rearrangements that occur frequently in the general population. Bioinformatics tools are now available for systematic genome-wide surveys of higher-order structures predisposing to such common variations in genomic architecture. Segmental duplications (SDs) constitute up to 5 per cent of the genome and play an important role in generating additional rearrangements and in disease aetiology. We conducted a genome-wide database search for a form of SD, palindromic segmental duplications (PSDs), which consist of paired, inverted duplications, and which predispose to inversions, duplications and deletions. The survey was complemented by a search for SDs in tandem orientation (TSDs) that can mediate duplications and deletions but not inversions. We found more than 230 distinct loci with higher-order genomic structure that can mediate genomic variation, of these about 180 contained a PSD. A number of these sites were previously identified as harbouring common inversions or as being associated with specific genomic diseases characterised by duplication, deletions or inversions. Most of the regions, however, were previously unidentified; their characterisation should identify further common rearrangements and may indicate localisations for additional genomic disorders. The widespread distribution of complex chromosomal architecture suggests a potentially high degree of plasticity of the human genome and could uncover another level of genetic variation within human populations

Workflow Management for Multiple Sclerosis Patients: IT and Organization

Patients with Multiple Sclerosis (MS) visit various healthcare providers during the course of their disease. It was suggested that IT might help to\ud orchestrate their care provision. We have applied the USE IT-tool to get insight in the relevant problems, solutions and constraints of the MS-care and the MS care providers both in the organizational and the information technological area. There is hardly a chain of healthcare, but rather, a network in which informal communication plays an important role. This informal network worked reasonably effective, but inefficient and slow. The patient himself plays a keyrole in information exchange between care-providers. Many providers were unaware of the services that other healthcare providers could give in general or did provide to a specific patient. MS patients-count is only small for most care providers. None of the interviewed patients mentioned a lack of contacts between careproviders as a problem. They thought that lack of\ud experience caused their major problems: insufficient and inadequate care. To improve care, we proposed a solution that combines a “short MS-protocol”, the\ud introduction of a central coordinator of care and a Patient Relation Management (PRM) System. This is a simple web-based application that is based on agreement by the caregivers that supports routing, tracking and tracing of a MS patient and supplies the caregivers with professional guidelines, as written down in the protocol. It is likely that we would have suggested a far more complicated ICT solution if we had only analyzed the MS-care process as such, without specific consideration of the USE IT dimensions

Managing technology risk in R&D project planning: Optimal timing and parallelization of R&D activities.

An inherent characteristic of R&D projects is technological uncertainty, which may result in project failure, and time and resources spent without any tangible return. In pharmaceutical projects, for instance, stringent scientific procedures have to be followed to ensure patient safety and drug efficacy in pre-clinical and clinical tests before a medicine can be approved for production. A project consists of several stages, and may have to be terminated in any of these stages, with typically a low likelihood of success. In project planning and scheduling, this technological uncertainty has typically been ignored, and project plans are developed only for scenarios in which the project succeeds. In this paper, we examine how to schedule projects in order to maximize their expected net present value, when the project activities have a probability of failure, and where an activity's failure leads to overall project termination. We formulate the problem, show that it is NP-hard and develop a branchand- bound algorithm that allows to obtain optimal solutions. We also present polynomial-time algorithms for special cases, and present a number of managerial insights for R&D project and planning, including the advantages and disadvantages of parallelization of R&D activities in different settings.Applications; Branch-and-bound; Computational complexity; Exact algorithms programming; Integer; Pharmaceutical; Project management; Project scheduling; R&D projects analysis of algorithms; Risk industries;

A hybrid scatter search. Electromagnetism meta-heuristic for project scheduling.

In the last few decades, several effective algorithms for solving the resource-constrained project scheduling problem have been proposed. However, the challenging nature of this problem, summarised in its strongly NP-hard status, restricts the effectiveness of exact optimisation to relatively small instances. In this paper, we present a new meta-heuristic for this problem, able to provide near-optimal heuristic solutions. The procedure combines elements from scatter search, a generic population-based evolutionary search method, and a recently introduced heuristic method for the optimisation of unconstrained continuous functions based on an analogy with electromagnetism theory, hereafter referred to as the electromagnetism meta-heuristic. We present computational experiments on standard benchmark datasets, compare the results with current state-ofthe-art heuristics, and show that the procedure is capable of producing consistently good results for challenging instances of the resource-constrained project scheduling problem. We also demonstrate that the algorithm outperforms state-of-the-art existing heuristics.Algorithms; Effectiveness; Electromagnetism; Functions; Heuristic; Project scheduling; Scatter; Scatter search; Scheduling; Theory;

Towards a better understanding of the e-health user: comparing USE IT and Requirements study for an Electronic Patient Record.

This paper compares a traditional requirements study with 22 interviews for the design of an electronic patient record (EPR) and a USE IT analysis with 17 interviews trying to understand the end- user of an EPR. Developing, implementing and using information technology in organizations is a complex social activity. It is often characterized by ill-defined problems or vague goals, conflicts and disruptions that result from organizational change. Successfully implementing information systems in healthcare organizations appears to be a difficult task. Information Technology is regarded as an enabler of change in healthcare organizations but (information) technology adoption decisions in healthcare are complex, because of the uncertainty of benefits and the rate of change of technology. (Job) Relevance is recognized as an important determinant for IS success but still does not find its way into a systems design process

Approximate Green's Function Coupled Cluster Method Employing Effective Dimension Reduction

The Green's function coupled cluster (GFCC) method is a powerful many-body tool for computing the electronic structure of molecular and periodic systems, especially when electrons of the system are strongly correlated. However, for the GFCC to be routinely used in the electronic structure calculations, robust numerical techniques and approximations must be employed to reduce its high computational overhead. In our recent studies, we demonstrated that the GFCC equations can be solved directly in the frequency domain using iterative linear solvers, which can be easily distributed in a massively parallel environment. In the present work, we demonstrate a successful application of model-order-reduction (MOR) techniques in the GFCC framework. Briefly, for a frequency regime which requires high resolution spectral function, instead of solving GFCC linear equation of full dimension for every single frequency point, an efficiently-solvable linear system model of a reduced dimension may be built upon projecting the original GFCC linear system onto a subspace. From this reduced order model is obtained a reasonable approximation to the full dimensional GFCC linear equations in both interpolative and extrapolative spectral regions. Here, we show that the subspace can be properly constructed in an iterative manner from the auxiliary vectors of the GFCC linear equations at some selected frequencies within the spectral region of interest. During the iterations, the quality of the subspace and the linear system model can be systematically improved. The method is tested in terms of the efficiency and accuracy of computing spectral functions for some typical molecular systems such as carbon monoxide, 1,3-butadiene, benzene, and adenine. As a byproduct, the obtained reduced order model may provide a high quality initial guess which improves the convergence rate for the existing iterative linear solver.Comment: 29 pages, 8 figure

Residence time distribution and hold-up in a cocurrent upflow packed bed reactor at elevated pressure

The residence time distribution in liquid phase was measured in a cocurrent upflow packed bed reactor for the system methanol-hydrogen at low Reynolds numbers and at elevated pressure. The plug flow with axial dispersion model was used to describe mixing in the system. The imperfect pulse method was used to measure the system response to a tracer pulse input. The parameters were calculated using the weighted moments method. The influence of the weighting factor was investigated. The experimental and theoretical outputs, as calculated by convolution, agreed very well. Different types of correlations were used for the Bodenstein number and liquid hold-up. From these correlations, the optimal one was selected for each parameter. A comparison was made between the ordinary moments and the weighted moments methods which led to the conclusion that the latter method is superior with respect to the accuracy of the estimated parameters and therefore strongly recommended