Structure and stability of non-symmetric Burgers vortices

We investigate, numerically and analytically, the structure and stability of steady and quasi-steady solutions of the Navier–Stokes equations corresponding to stretched vortices embedded in a uniform non-symmetric straining field, ([alpha]x, [beta]y, [gamma]z), [alpha]+[beta]+[gamma]=0, one principal axis of extensional strain of which is aligned with the vorticity. These are known as non-symmetric Burgers vortices (Robinson & Saffman 1984). We consider vortex Reynolds numbers R=[Gamma]/(2[pi]v) where [Gamma] is the vortex circulation and v the kinematic viscosity, in the range R=1[minus sign]104, and a broad range of strain ratios [lambda]=([beta][minus sign][alpha])/([beta]+[alpha]) including [lambda]>1, and in some cases [lambda][dbl greater-than sign]1. A pseudo-spectral method is used to obtain numerical solutions corresponding to steady and quasi-steady vortex states over our whole (R, [lambda]) parameter space including [lambda] where arguments proposed by Moffatt, Kida & Ohkitani (1994) demonstrate the non-existence of strictly steady solutions. When [lambda][dbl greater-than sign]1, R[dbl greater-than sign]1 and [epsilon][identical with][lambda]/R[double less-than sign]1, we find an accurate asymptotic form for the vorticity in a region 11. An iterative technique based on the power method is used to estimate the largest eigenvalues for the non-symmetric case [lambda]>0. Stability is found for 0[less-than-or-eq, slant][lambda][less-than-or-eq, slant]1, and a neutrally convective mode of instability is found and analysed for [lambda]>1. Our general conclusion is that the generalized non-symmetric Burgers vortex is unconditionally stable to two-dimensional disturbances for all R, 0[less-than-or-eq, slant][lambda][less-than-or-eq, slant]1, and that when [lambda]>1, the vortex will decay only through exponentially slow leakage of vorticity, indicating extreme robustness in this case

Balancing scientific interests and the rights of participants in designing a recall by genotype study

Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South Tyrol (CHRIS) study is a longitudinal cohort study based in South Tyrol, Italy. Demand has grown for CHRIS study participants to be enrolled in RbG studies, thus making the design of a suitable ethical framework a pressing need. We here report upon the design of a pilot RbG study conducted with CHRIS study participants. By reviewing the literature and by consulting relevant stakeholders (CHRIS participants, clinical geneticists, ethics board, GPs), we identified key ethical issues in RbG approaches (e.g. complexity of the context, communication of genetic results, measures to further protect participants). The design of the pilot was based on a feasibility assessment, the selection of a suitable test case within the ProtectMove Research Unit on reduced penetrance of hereditary movement disorders, and the development of appropriate recruitment and communication strategies. An empirical study was embedded in the pilot study with the aim of understanding participants’ views on RbG. Our experience with the pilot study in CHRIS allowed us to contribute to the development of best practices and policies for RbG studies by drawing recommendations: addressing the possibility of RbG in the original consent, implementing tailored communication strategies, engaging stakeholders, designing embedded empirical studies, and sharing research experiences and methodology

Posture and low back pain during pregnancy — 3D study

Objectives: Back pain is a common complaint of pregnant women. The posture, curvatures of the spine and the center of gravity changes are considered as the mechanisms leading to pain. The study aimed to assess spinal curvatures and static postural characteristics with three-dimensional surface topography and search for relationships with the occurrence of back pain complaints among pregnant women. Material and methods: The study was conducted from December 2012 to February 2014. Patients referred from University Clinic of Gynecology and Obstetrics were examined outpatient at the Posture Study Unit of Department of Orthopaedics and Traumatology. Sixty-five women at 4–39 weeks of pregnancy were assessed and surveyed with Oswestry Disability Index; posture was evaluated using surface topography. Results: The study confirmed that difficulties in sitting and standing are significant in the third trimester of the pregnancy. The overall tendency for significant lumbar curvature changes in pregnant women was not confirmed. Major changes in sagittal trunk inclination in relation to the plumb line were not observed in the study group. Conclusions: The issue regarding how the pregnancy causes changes in spinal curvature and posture remains open for further studies. Presented method of 3D surface topography can reveal postural changes, but that requires several exams of each subject and strict follow-up of the series of cases

A Rare Disease Patient Manager

ABSTRACT publicado: 6th International Conference on Practical Applications of Computational Biology & Bioinformatics (PACBB. Salamanca, 28-30 Março 2012The personal health implications behind rare diseases are seldom considered in widespread medical care. The low incidence rate and complex treatment process makes rare disease research an underrated field in the life sciences. However, it is in these particular conditions that the strongest relations between genotypes and phenotypes are identified. The rare disease patient manager, detailed in this manuscript, presents an innovative perspective for a patient-centric portal integrating genetic and medical data. With this strategy, patient’s digital records are transparently integrated and connected to wet-lab genetics research in a seamless working environment. The resulting knowledge base offers multiple data views, geared towards medical staff, with patient treatment and monitoring data; genetics researchers, through a custom locus-specific database; and patients, who for once play an active role in their treatment and rare diseases research

The Slavic NBN founder mutation: a role for reproductive fitness?

The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Notably, not a single parenthood of a homozygous c.657del5 carrier has been reported to date, while heterozygous carriers do reproduce but have an increased cancer risk. These observations seem to conflict with the considerable carrier frequency of c.657del5 of 0.5% to 1% as observed in different Slavic populations because deleterious mutations would be eliminated quite rapidly by purifying selection. Therefore, we propose that heterozygous c.657del5 carriers have increased reproductive success, i.e., that the mutation confers heterozygote advantage. In fact, in our cohort study of the reproductive history of 24 NBS pedigrees from the Czech Republic, we observed that female carriers gave birth to more children on average than female non-carriers, while no such reproductive differences were observed for males. We also estimate that c.657del5 likely occurred less than 300 generations ago, thus supporting the view that the original mutation predated the historic split and subsequent spread of the 'Slavic people'. We surmise that the higher fertility of female c.657del5 carriers reflects a lower miscarriage rate in these women, thereby reflecting the role of the NBN gene product, nibrin, in the repair of DNA double strand breaks and their processing in immune gene rearrangements, telomere maintenance, and meiotic recombination, akin to the previously described role of the DNA repair genes BRCA1 and BRCA2

Genome-wide association analysis and fine mapping of NT-proBNP level provide novel insight into the role of the MTHFR-CLCN6-NPPA-NPPB gene cluster

High blood concentration of the N-terminal cleavage product of the B-type natriuretic peptide (NT-proBNP) is strongly associated with cardiac dysfunction and is increasingly used for heart failure diagnosis. To identify genetic variants associated with NT-proBNP level, we performed a genome-wide association analysis in 1325 individuals from South Tyrol, Italy, and followed up the most significant results in 1746 individuals from two German population-based studies. A genome-wide significant signal in the MTHFR-CLCN6-NPPA-NPPB gene cluster was replicated, after correction for multiple testing (replication one-sided P-value = 8.4 × 10−10). A conditional regression analysis of 128 single-nucleotide polymorphisms in the region of interest identified novel variants in the CLCN6 gene as independently associated with NT-proBNP. In this locus, four haplotypes were associated with increased NT-proBNP levels (haplotype-specific combined P-values from 8.3 × 10−03 to 9.3 × 10−11). The observed increase in the NT-proBNP level was proportional to the number of haplotype copies present (i.e. dosage effect), with an increase associated with two copies that varied between 20 and 100 pg/ml across populations. The identification of novel variants in the MTHFR-CLCN6-NPPA-NPPB cluster provides new insights into the biological mechanisms of cardiac dysfunction

'Sifting the significance from the data' - the impact of high-throughput genomic technologies on human genetics and health care.

This report is of a round-table discussion held in Cardiff in September 2009 for Cesagen, a research centre within the Genomics Network of the UK's Economic and Social Research Council. The meeting was arranged to explore ideas as to the likely future course of human genomics. The achievements of genomics research were reviewed, and the likely constraints on the pace of future progress were explored. New knowledge is transforming biology and our understanding of evolution and human disease. The difficulties we face now concern the interpretation rather than the generation of new sequence data. Our understanding of gene-environment interaction is held back by our current primitive tools for measuring environmental factors, and in addition, there may be fundamental constraints on what can be known about these complex interactions.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Identification and characterisation of a novel GHR defect disrupting the polypyrimidine tract and resulting in GH insensitivity

Objective GH insensitivity (GHI) is caused in the majority of cases by impaired function of the GH receptor (GHR). All but one known GHR mutation are in the coding sequence or the exon/intron boundaries. We identified and characterised the first intronic defect occurring in the polypyrimidine tract of the GHR in a patient with severe GHI. Design We investigated the effect of the novel defect on mRNA splicing using an in vitro splicing assay and a cell transfection system. Methods GHR was analysed by direct sequencing. To assess the effect of the novel defect, two heterologous minigenes (wild-type and mutant L1-GHR8-L2) were generated by inserting GHR exon 8 and its flanking wild-type or mutant intronic sequences into a well-characterised splicing reporter (Adml-par L1–L2). 32P-labelled pre-mRNA was generated from the two constructs and incubated in HeLa nuclear extracts or HEK293 cells. Results Sequencing of the GHR revealed a novel homozygous defect in the polypyrimidine tract of intron 7 (IVS7-6T>A). This base change does not involve the highly conserved splice site sequences, and is not predicted in silico to affect GHR mRNA splicing. Nevertheless, skipping of exon 8 from the mutant L1-GHR8-L2 mRNA was clearly demonstrated in the in vitro splicing assay and in transfected HEK293 cells. Conclusion Disruption of the GHR polypyrimidine tract causes aberrant mRNA splicing leading to a mutant GHR protein. This is predicted to lack its transmembrane and intracellular domains and, thus, be incapable of transducing a GH signal