Multiple evolutionary rate classes in animal genome evolution

The proportion of functional sequence in the human genome is currently a subject of debate. The most widely accepted figure is that approximately 5% is under purifying selection. In Drosophila, estimates are an order of magnitude higher, though this corresponds to a similar quantity of sequence. These estimates depend on the difference between the distribution of genomewide evolutionary rates and that observed in a subset of sequences presumed to be neutrally evolving. Motivated by the widening gap between these estimates and experimental evidence of genome function, especially in mammals, we developed a sensitive technique for evaluating such distributions and found that they are much more complex than previously apparent. We found strong evidence for at least nine well-resolved evolutionary rate classes in an alignment of four Drosophila species and at least seven classes in an alignment of four mammals, including human. We also identified at least three rate classes in human ancestral repeats. By positing that the largest of these ancestral repeat classes is neutrally evolving, we estimate that the proportion of nonneutrally evolving sequence is 30% of human ancestral repeats and 45% of the aligned portion of the genome. However, we also question whether any of the classes represent neutrally evolving sequences and argue that a plausible alternative is that they reflect variable structure-function constraints operating throughout the genomes of complex organisms.

Multiple types of child maltreatment and adolescent mental health in Viet Nam

Objective To examine the prevalence of multiple types of maltreatment (MTM), potentially confounding factors and associations with depression, anxiety and self-esteem among adolescents in Viet Nam. Methods In 2006 we conducted a cross-sectional survey of 2591 students (aged 12–18 years; 52.1% female) from randomly-selected classes in eight secondary schools in urban (Hanoi) and rural (Hai Duong) areas of northern Viet Nam (response rate, 94.7%). Sequential multiple regression analyses were performed to estimate the relative influence of individual, family and social characteristics and of eight types of maltreatment, including physical, emotional and sexual abuse and physical or emotional neglect, on adolescent mental health. Findings Females reported more neglect and emotional abuse, whereas males reported more physical abuse, but no statistically significant difference was found between genders in the prevalence of sexual abuse. Adolescents were classified as having nil (32.6%), one (25.9%), two (20.7%), three (14.5%) or all four (6.3%) maltreatment types. Linear bivariate associations between MTM and depression, anxiety and low self-esteem were observed. After controlling for demographic and family factors, MTM showed significant independent effects. The proportions of the variance explained by the models ranged from 21% to 28%. Conclusion The combined influence of adverse individual and family background factors and of child maltreatment upon mental health in adolescents in Viet Nam is consistent with research in non-Asian countries. Emotional abuse was strongly associated with each health indicator. In Asian communities where child abuse is often construed as severe physical violence, it is important to emphasize the equally pernicious effects of emotional maltreatment.

Multiple analysis of three common genetic alterations associated with thrombophilia

We have previously reported the use of a novel mini-sequencing protocol for detection of the factor V Leiden variant, the first nucleotide change (FNC) technology. This technology is based on a single nucleotide extension of a primer, which is hybridized immediately adjacent to the site of mutation. The extended nucleotide that carries a reporter molecule (fluorescein) has the power to discriminate the genotype at the site of mutation. More recently, the prothrombin 20210 and thermolabile methylene tetrahydrofolate reductase (MTHFR) 677 variants have been identified as possible risk factors associated with thrombophilia. This study describes the use of the FNC technology in a combined assay to detect factor V, prothrombin and MTHFR variants in a population of Australian blood donors, and describes the objective numerical methodology used to determine genotype cut-off values for each genetic variation. Using FNC to test 500 normal blood donors, the incidence of Factor V Leiden was 3.6% (all heterozygous), that of prothrombin 20210 was 2.8% (all heterozygous) and that of MTHFR was 10% (homozygous). The combined FNC technology offers a simple, rapid, automatable DNA-based test for the detection of these three important mutations that are associated with familial thrombophilia. (C) 2000 Lippincott Williams and Wilkins.

Live my work : rural nurses and their multiple perspectives of self

Aim. This paper is a report of a study to explore rural nurses' experiences of mentoring. Background. Mentoring has recently been proposed by governments, advocates and academics as a solution to the problem for retaining rural nurses in the Australian workforce. Action in the form of mentor development workshops has changed the way that some rural nurses now construct supportive relationships as mentoring. Method. A grounded theory design was used with nine rural nurses. Eleven semi-structured interviews were conducted in various states of Australia during 2004-2005. Situational analysis mapping techniques and frame analysis were used in combination with concurrent data generation and analysis and theoretical sampling. Findings. Experienced rural nurses cultivate novices through supportive mentoring relationships. The impetus for such relationships comes from their own histories of living and working in the same community, and this was termed 'live my work'. Rural nurses use multiple perspectives of self in order to manage their interactions with others in their roles as community members, consumers of healthcare services and nurses. Personal strategies adapted to local context constitute the skills that experienced rural nurses pass-on to neophyte rural nurses through mentoring, while at the same time protecting them through troubleshooting and translating local cultural norms. Conclusion. Living and working in the same community creates a set of complex challenges for novice rural nurses that are better faced with a mentor in place. Thus, mentoring has become an integral part of experienced rural nurses' practice to promote staff retention. © 2007 The Authors.

A unifying view of multiple kernel learning

Recent research on multiple kernel learning has lead to a number of approaches for combining kernels in regularized risk minimization. The proposed approaches include different formulations of objectives and varying regularization strategies. In this paper we present a unifying optimization criterion for multiple kernel learning and show how existing formulations are subsumed as special cases. We also derive the criterion’s dual representation, which is suitable for general smooth optimization algorithms. Finally, we evaluate multiple kernel learning in this framework analytically using a Rademacher complexity bound on the generalization error and empirically in a set of experiments.

A unifying view of multiple kernel learning

Recent research on multiple kernel learning has lead to a number of approaches for combining kernels in regularized risk minimization. The proposed approaches include different formulations of objectives and varying regularization strategies. In this paper we present a unifying general optimization criterion for multiple kernel learning and show how existing formulations are subsumed as special cases. We also derive the criterion's dual representation, which is suitable for general smooth optimization algorithms. Finally, we evaluate multiple kernel learning in this framework analytically using a Rademacher complexity bound on the generalization error and empirically in a set of experiments.