Using Quasi-variance to Communicate Sociological Results from Statistical Models

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Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Methods for exact perturbation analysis

1. The dominant eigenvalue of the population projection matrix provides the asymptotic growth rate of a population. Perturbation analysis examines how changes in vital rates affect this rate. The standard approach to evaluating the effect of a perturbation uses sensitivities and elasticities to provide a linear approximation, which is often inappropriate. 2. A transfer function approach provides the exact relationship between growth rate and perturbation. An alternative approach derives the exact solution using symbolic algebra by calculating the matrix characteristic equation in terms of the perturbation parameters and the symptotic growth rate. 3. This provides integrated sensitivities and plots of the exact relationship. The same method may be used for any perturbation structure, however complicated. 4. The simplicity of the new method is illustrated through two examples - the killer whale and the lizard orchid

Assessment of somaclonal variation in apple. I.Resistance to the fire blight pathogen, Erwinia amylovora

After inoculation of glasshouse-grown somaclones regenerated from apple leaf discs (cv. Greensleeves) 33% of 270 showed an increase in resistance to the fire blight pathogen Erwinia amylovora. In contrast only 21% produced less severe symptoms than parental material after inoculation of plants held in culture in vitro. Sixteen somaclones which showed the highest levels of fire blight resistance were tested intensively as both glasshouse-grown plants and as micropropagated plants in culture. In tests conducted with glasshouse-grown plants up to 60% of plants of the most promising somaclones exhibited minimum symptoms after inoculation compared with 4% of \u2018Greensleeves\u2019 parental plants. The comparable figures for inoculations of in vitro cultured plants were 70% and 8%. The growth of E. amylovora was reduced in resistant somaclones compared with parental plants. Pretreating leaf discs with virulent E. amylovora cells prior to somaclone regeneration had no effect on the frequency of regenerated somaclones exhibiting increased resistance to the pathogen