19711359
Clues to function in gene deserts.
Recent work by Ivan Ovcharenko and colleagues has shed new light on the functional importance of gene deserts. They demonstrate that sequence conservation levels separate gene deserts into stable (more conserved) and variable classes. Both classes exhibit characteristics suggestive of function. The stable deserts in particular show features suggesting a role in the complex regulation of core vertebrate genes.
14002416
Strong and weak male mutation bias at different sites in the primate genomes: insights from the human-chimpanzee comparison.
Male mutation bias is a higher mutation rate in males than in females thought to result from the greater number of germ line cell divisions in males. If errors in DNA replication cause most mutations, then the magnitude of male mutation bias, measured as the male-to-female mutation rate ratio (alpha), should reflect the relative excess of male versus female germ line cell divisions. Evolutionary rates averaged among all sites in a sequence and compared between mammalian sex chromosomes were shown to be indeed higher in males than in females. However, it is presently unknown whether individual classes of substitutions exhibit such bias. To address this issue, we investigated male mutation bias separately at non-CpG and CpG sites using human-chimpanzee whole-genome alignments. We observed strong male mutation bias at non-CpG sites: alpha in the X-autosome comparison was approximately 6-7, which was similar to the male-to-female ratio in the number of germ line cell divisions. In contrast, mutations at CpG sites exhibited weak male mutation bias: alpha in the X-autosome comparison was only approximately 2-3. This is consistent with the methylation-induced and replication-independent mechanism of CpG transitions, which constitute the majority of mutations at CpG sites. Interestingly, our study also indicated weak male mutation bias for transversions at CpG sites, implying a spontaneous mechanism largely not associated with replication. Male mutation bias was equally strong at CpG and non-CpG sites located within unmethylated "CpG islands," suggesting the replication-dependent origin of these mutations. Thus, we found that the strength of male mutation bias is nonuniform in the primate genomes. Importantly, we discovered that male mutation bias depends on the proportion of CpG sites in the loci compared. This might explain the differences in the magnitude of primate male mutation bias observed among studies.
13468480
ESPERR: learning strong and weak signals in genomic sequence alignments to identify functional elements.
Genomic sequence signals - such as base composition, presence of particular motifs, or evolutionary constraint - have been used effectively to identify functional elements. However, approaches based only on specific signals known to correlate with function can be quite limiting. When training data are available, application of computational learning algorithms to multispecies alignments has the potential to capture broader and more informative sequence and evolutionary patterns that better characterize a class of elements. However, effective exploitation of patterns in multispecies alignments is impeded by the vast number of possible alignment columns and by a limited understanding of which particular strings of columns may characterize a given class. We have developed a computational method, called ESPERR (evolutionary and sequence pattern extraction through reduced representations), which uses training examples to learn encodings of multispecies alignments into reduced forms tailored for the prediction of chosen classes of functional elements. ESPERR produces a greatly improved Regulatory Potential score, which can discriminate regulatory regions from neutral sites with excellent accuracy ( approximately 94%). This score captures strong signals (GC content and conservation), as well as subtler signals (with small contributions from many different alignment patterns) that characterize the regulatory elements in our training set. ESPERR is also effective for predicting other classes of functional elements, as we show for DNaseI hypersensitive sites and highly conserved regions with developmental enhancer activity. Our software, training data, and genome-wide predictions are available from our Web site (http://www.bx.psu.edu/projects/esperr).
32584830
Genetic and Environmental Influences on Psychopathy Trait Dimensions in a Community Sample of Male Twins
Psychopathy appears to be comprised of two broad dimensions: impulsivity/antisocial behavior and interpersonal detachment/callousness. This study examined the extent to which variance in these 2 psychopathy trait dimensions was associated with common or unique genetic, shared, and nonshared environmental factors in two independent samples of reared together 16–18-year-old male twins. One sample included 142 monozygotic (MZ) and 70 dizygotic (DZ) pairs; the other sample included 128 MZ and 58 DZ pairs. Boys completed the Minnesota Temperament Inventory (MTI), a 19-item measure that contains separate subscales: Antisocial and Detachment. Variance in the Antisocial and Detachment scales was associated with additive genetic factors and neither scale was associated with shared environmental factors. As expected, the bivariate biometric analysis suggested genetic influence on the covariance of the scales. The results are consistent with theoretical models of psychopathy that posit some independence in the etiology of the two major trait dimensions of psychopathy.
24733801
Salutogenesis as a framework for child protection: literature review.
AIM
The aim of this paper is to demonstrate the usefulness of salutogenesis in work relating to child protection.


METHODS
A systematic review to explore the links between parenting, social factors and failure to thrive was carried out using 17 CD ROM and online databases using keywords in appropriate medical subject headings (MeSH terms) and Boolean operators refined for the studies. The salutogenic framework was then used as a way of clarifying what benefit particular research findings may have in identifying and using factors which can be associated with protection, safety and well being of children. Cross-referencing the evidence from the systematic review against Antonovsky's generalized resistance resources created a salutogenic matrix.


FINDINGS
Four factors in the systematic review were found crucially important: parent factors; parenting factors; child factors; and social factors. However, it is probable that these are useful within all child protection research and the evidence gathered in particular cases (here failure to thrive) could be plotted against each factor. Application of a salutogenic framework to the results was further illuminating and has utility for both systematic review methodology and other child protection explorations. The matrix created a warp and weft effect that identified gaps in current evidence and practice and was able to disentangle some of the complexities inherent within failure to thrive situations. By beginning to shed understanding on such processes, the concept of salutogenesis added further depth and rigour to the analysis.


CONCLUSIONS
The concept of salutogenesis is widely used in some areas of nursing practice and research, and can also be regarded as a theoretical tool that has potential in child care and protection research, development and practice. The paper also illustrates the importance of a sound theoretical framework in ensuring depth and rigour in analyses of literature review findings.
14886641
The 'miss rate' for the analysis of gene expression data.
Multiple testing issues are important in gene expression studies, where typically thousands of genes are compared over two or more experimental conditions. The false discovery rate has become a popular measure in this setting. Here we discuss a complementary measure, the 'miss rate', and show how to estimate it in practice.
16183837
The modifying effect of the building envelope on population exposure to PM2.5 from outdoor sources
A number of studies have estimated population exposure to PM2.5 by examining modeled or measured outdoor PM2.5 levels. However, few have taken into account the mediating effects of building characteristics on the ingress of PM2.5 from outdoor sources and its impact on population exposure in the indoor domestic environment. This study describes how building simulation can be used to determine the indoor concentration of outdoor-sourced pollution for different housing typologies and how the results can be mapped using building stock models and Geographical Information Systems software to demonstrate the modifying effect of dwellings on occupant exposure to PM2.5 across London. Building archetypes broadly representative of those in the Greater London Authority were simulated for pollution infiltration using EnergyPlus. In addition, the influence of occupant behavior on indoor levels of PM2.5 from outdoor sources was examined using a temperature-dependent window-opening scenario. Results demonstrate a range of I/O ratios of PM2.5, with detached and semi-detached dwellings most vulnerable to high levels of infiltration. When the results are mapped, central London shows lower I/O ratios of PM2.5 compared with outer London, an apparent inversion of exposure most likely caused by the prevalence of flats rather than detached or semi-detached properties.
18213491
The smacking controversy: what advice should we be giving parents?
BACKGROUND
Even among countries that have ratified the United Nations Convention on the Rights of the Child there is much disagreement about corporal punishment of children. Last year the Scottish Executive proposed a new law banning the smacking of children under the age of three, becoming the tenth European nation to do so. The proposal, currently abandoned whilst ostensibly still under debate, has raised a wave of controversy in child protection circles. In the nearest neighbouring country, England, a similar proposal was robustly rejected. PURPOSE OF THE PAPER: Given an increasing family and community focus in nursing, the implications of the debate for the profession cannot be ignored. What should we be telling 'ordinary' families about smacking? Thus this paper presents a positional statement on the smacking controversy and outlines some pointers for practice.


DISCUSSION
While for many the legislation proposed does not go far enough, others decry it as a breach of parental rights and, thus, the issue has become hugely controversial. Media opinion and various opposing campaigns dominate both public and professional spheres. Rights, responsibilities, examples from other countries, culture and gender are all used as fodder in the debate. Extreme examples are cited by both sides and used as grist for what are at times tenuous arguments. As there is even a division within child protection arenas, practising professionals may struggle to find a way through the maze of seemingly contradictory findings from research, policy and opinion.


CONCLUSIONS
A wide range of literature suggests that both public and professional opinion is divided on the use of smacking as a form of discipline of young children. Opinion is also divided on the ability of legislation to bring about change in social attitudes and behaviour. Health care professionals need to be in a position to recommend best practice and to do so consistently.