Formation of regulatory modules by local sequence duplication

Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here, we show that a large fraction of neighboring transcription factor binding sites in the fly genome have formed from a common sequence origin by local duplications. This mode of evolution is found to produce regulatory information: duplications can seed new sites in the neighborhood of existing sites. Duplicate seeds evolve subsequently by point mutations, often towards binding a different factor than their ancestral neighbor sites. These results are based on a statistical analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome, and a comparison set of intergenic regulatory sequence in Saccharomyces cerevisiae. In fly regulatory modules, pairs of binding sites show significantly enhanced sequence similarity up to distances of about 50 bp. We analyze these data in terms of an evolutionary model with two distinct modes of site formation: (i) evolution from independent sequence origin and (ii) divergent evolution following duplication of a common ancestor sequence. Our results suggest that pervasive formation of binding sites by local sequence duplications distinguishes the complex regulatory architecture of higher eukaryotes from the simpler architecture of unicellular organisms

The contrast-enhanced Doppler ultrasound with perfluorocarbon exposed sonicated albumin does not improve the diagnosis of renal artery stenosis compared with angiography

There are no studies investigating the effect of the contrast infusion on the sensitivity and specificity of the main Doppler criteria of renal artery stenosis (RAS). Our aim was to evaluate the accuracy of these Doppler criteria prior to and following the intravenous administration of perfluorocarbon exposed sonicated albumin (PESDA) in patients suspected of having RAS. Thirty consecutive hypertensive patients (13 males, mean age of 57 ± 10 years) suspected of having RAS by clinical clues, were submitted to ultrasonography (US) of renal arteries before and after enhancement using continuous infusion of PESDA. All patients underwent angiography, and haemodynamically significant RAS was considered when ≥50%. At angiography, it was detected RAS ≥50% in 18 patients, 5 with bilateral stenosis. After contrast, the examination time was slightly reduced by approximately 20%. In non-enhanced US the sensitivity was better when based on resistance index (82.9%) while the specificity was better when based on renal aortic ratio (89.2%). The predictive positive value was stable for all indexes (74.0%–88.0%) while negative predictive value was low (44%–51%). The specificity and positive predictive value based on renal aortic ratio increased after PESDA injection respectively, from 89 to 97.3% and from 88 to 95%. In hypertensives suspected to have RAS the sensitivity and specificity of Duplex US is dependent of the criterion evaluated. Enhancement with continuous infusion of PESDA improves only the specificity based on renal aortic ratio but do not modify the sensitivity of any index

The effectiveness of interventions to change six health behaviours: a review of reviews

Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency). Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis. Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities. Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p

So Different, yet So Similar: Meta-Analysis and Policy Modeling of Willingness to Participate in Clinical Trials among Brazilians and Indians

BACKGROUND: With the global expansion of clinical trials and the expectations of the rise of the emerging economies known as BRICs (Brazil, Russia, India and China), the understanding of factors that affect the willingness to participate in clinical trials of patients from those countries assumes a central role in the future of health research. METHODS: We conducted a systematic review and meta-analysis (SRMA) of willingness to participate in clinical trials among Brazilian patients and then we compared it with Indian patients (with results of another SRMA previously conducted by our group) through a system dynamics model. RESULTS: Five studies were included in the SRMA of Brazilian patients. Our main findings are 1) the major motivation for Brazilian patients to participate in clinical trials is altruism, 2) monetary reimbursement is the least important factor motivating Brazilian patients, 3) the major barrier for Brazilian patients to not participate in clinical trials is the fear of side effects, and 4) Brazilian patients are more likely willing to participate in clinical trials than Indians. CONCLUSION: Our study provides important insights for investigators and sponsors for planning trials in Brazil (and India) in the future. Ignoring these results may lead to unnecessary fund/time spending. More studies are needed to validate our results and for better understanding of this poorly studied theme

Life History of Female Preferences for Male Faces: A Comparison of Pubescent Girls, Nonpregnant and Pregnant Young Women, and Middle-aged Women

Although scientific interest in facial attractiveness has developed substantially in recent years, few studies have contributed to our understanding of the ontogeny of facial preferences. In this study, attractiveness of 30 male faces was evaluated by four female groups: girls at puberty, nonpregnant and pregnant young women, and middle-aged women. The main findings are as follows: (1) Preference for sexy-looking faces was strongest in young, nonpregnant women. (2) Biologically more mature girls displayed more adultlike preferences. (3) The intragroup consistency for postmenopausal women was relatively low. (4) In terms of the preference pattern, pregnant women were more similar to perimenopausal women than they were to their nonpregnant peers. (5) Preference for youthful appearance decreased with the age of the women. I argue that the life history of female preferences for male faces is, to a large extent, hormone-driven and underpinned by a set of evolutionary adaptations

Brazilian adolescents' knowledge and beliefs about abortion methods: A school-based internet inquiry

Background: Internet surveys that draw from traditionally generated samples provide the unique conditions to engage adolescents in exploration of sensitive health topics.Methods: We examined awareness of unwanted pregnancy, abortion behaviour, methods, and attitudes toward specific legal indications for abortion via a school-based internet survey among 378 adolescents aged 12-21 years in three Rio de Janeiro public schools.Results: Forty-five percent knew peers who had undergone an abortion. Most students (66.0%) did not disclose abortion method knowledge. However, girls (aOR 4.2, 95% CI 2.4-7.2), those who had experienced their sexual debut (aOR1.76, 95% CI 1.1-3.0), and those attending a prestigious magnet school (aOR 2.7 95% CI 1.4-6.3) were more likely to report methods. Most abortion methods (79.3%) reported were ineffective, obsolete, and/or unsafe. Herbs (e.g. marijuana tea), over-the-counter medications, surgical procedures, foreign objects and blunt trauma were reported. Most techniques (85.2%) were perceived to be dangerous, including methods recommended by the World Health Organization. A majority (61.4%) supported Brazil's existing law permitting abortion in the case of rape. There was no association between gender, age, sexual debut, parental education or socioeconomic status and attitudes toward legal abortion. However, students at the magnet school supported twice as many legal indications (2.7, SE.27) suggesting a likely role of peers and/or educators in shaping abortion views.Conclusions: Abortion knowledge and attitudes are not driven simply by age, religion or class, but rather a complex interplay that includes both social spaces and gender. Prevention of abortion morbidity and mortality among adolescents requires comprehensive sexuality and reproductive health education that includes factual distinctions between safe and unsafe abortion methods

Predictors of early sexual initiation among a nationally representative sample of Nigerian adolescents

<p>Abstract</p> <p>Background</p> <p>Early sexual debut among adolescents is associated with considerable negative heath and development outcomes. An understanding of the determinants or predictors of the timing of sexual debut is important for effective intervention, but very few studies to date have addressed this issue in the Nigerian context. The aim of the present study is to examine predictors of adolescent sexual initiation among a nationally representative sample of adolescents in Nigeria.</p> <p>Methods</p> <p>Interviewer-collected data of 2,070 never-married adolescents aged 15–19 years were analysed to determine association between age of sexual debut and demographic, psychosocial and community factors. Using Cox proportional hazards regression multivariate analysis was carried out with two different models – one with and the other without psychosocial factors. Hazard ratio (HR) and 95% confidence interval (CI) were calculated separately for males and females.</p> <p>Results</p> <p>A fifth of respondents (18% males; 22% females) were sexually experienced. In the South 24.3% males and 28.7% females had initiated sex compared to 12.1% of males and 13.1% females in the North (p < 0.001). In the first model, only region was significantly associated with adolescent sexual initiation among both males and females; however, educational attainment and age were also significant among males. In the second (psychosocial) model factors associated with adolescent sexual debut for both genders included more positive attitudes regarding condom efficacy (males: HR = 1.28, 95% CI = 1.07–1.53; females: HR = 1.24, 95% CI = 1.05–1.46) and more positive attitudes to family planning use (males: HR = 1.19, 95% CI = 1.09–1.31; females: HR = 1.18, 95% CI = 1.07–1.30). A greater perception of condom access (HR = 1.42, 95% CI = 1.14–1.76) and alcohol use (HR = 1.90, 95% CI = 1.38–2.62) among males and positive gender-related attitudes (HR = 1.13, 95% CI = 1.04–1.23) among females were also associated with increased likelihood of adolescent sexual initiation. Conversely, personal attitudes in favour of delayed sexual debut were associated with lower sexual debut among both males (males: HR = 0.36, 95% CI = 0.25–0.52) and females (HR = 0.38, 95% CI = 0.25–0.57). Higher level of religiosity was associated with lower sexual debut rates only among females (HR = 0.59, 95% CI = 0.37–0.94).</p> <p>Conclusion</p> <p>Given the increased risk for a number of sexually transmitted health problems, understanding the factors that are associated with premarital sexual debut will assist programmes in developing more effective risk prevention interventions.</p

Finding regulatory elements and regulatory motifs: a general probabilistic framework

Over the last two decades a large number of algorithms has been developed for regulatory motif finding. Here we show how many of these algorithms, especially those that model binding specificities of regulatory factors with position specific weight matrices (WMs), naturally arise within a general Bayesian probabilistic framework. We discuss how WMs are constructed from sets of regulatory sites, how sites for a given WM can be discovered by scanning of large sequences, how to cluster WMs, and more generally how to cluster large sets of sites from different WMs into clusters. We discuss how 'regulatory modules', clusters of sites for subsets of WMs, can be found in large intergenic sequences, and we discuss different methods for ab initio motif finding, including expectation maximization (EM) algorithms, and motif sampling algorithms. Finally, we extensively discuss how module finding methods and ab initio motif finding methods can be extended to take phylogenetic relations between the input sequences into account, i.e. we show how motif finding and phylogenetic footprinting can be integrated in a rigorous probabilistic framework. The article is intended for readers with a solid background in applied mathematics, and preferably with some knowledge of general Bayesian probabilistic methods. The main purpose of the article is to elucidate that all these methods are not a disconnected set of individual algorithmic recipes, but that they are just different facets of a single integrated probabilistic theory

Psychological distress during pregnancy in a multi-ethnic community: findings from the born in Bradford cohort study

Purpose: Antenatal anxiety and depression are predictive of future mental distress, which has negative effects on children. Ethnic minority women are more likely to have a lower socio-economic status (SES) but it is unclear whether SES is an independent risk factor for mental health in pregnancy. We described the association between maternal mental distress and socio-demographic factors in a multi-ethnic cohort located in an economically deprived city in the UK. Methods: We defined eight distinct ethno-language groups (total N = 8,454) and classified a threshold of distress as the 75th centile of within-group GHQ-28 scores, which we used as the outcome for univariate and multivariate logistic regression for each ethnic group and for the sample overall. Results: Financial concerns were strongly and independently associated with worse mental health for six out of the eight ethnic groups, and for the cohort overall. In some groups, factors such as working status, education and family structure were associated with worse mental health, but for others these factors were of little importance. Conclusions: The diversity between and within ethnic groups in this sample underlines the need to take into consideration individual social, migration and economic circumstances and their potential effect on mental health in ethnically diverse areas

Relationship Contexts as Sources of Socialization: An Exploration of Intimate Partner Violence Experiences of Economically Disadvantaged African American Adolescents

Intimate partner violence (IPV) among African Americans is a serious public health concern. Research suggest that African Americans adolescents, particularly those from economically disadvantaged communities, are at heightened risk for experiencing and perpetrating dating violence compared to youth from other racial and ethnic groups. In the present study, we examined different relationship contexts that are sources of IPV socialization. Semi-structured interviews were conducted with 22 economically disadvantaged African American adolescents. Content analysis yielded five relationship contexts through which the participants witnessed, experienced, and perpetrated IPV: (a) adolescents’ own dating relationships (64%), (b) siblings and extended family members (e.g., cousins, aunts, uncles) (59%), (c) parent-partners (27%), (d) friends (23%), and (e) neighbors (18%). Adolescents also frequently described IPV in their own dating relationships and in parent-partner relationships as mutual. Moreover, they appeared to minimize the experience of IPV in their own relationships. Efforts to reduce rates of IPV among economically disadvantaged African American adolescents should consider these relational contexts through which adolescents are socialized with regards to IPV and adolescents’ beliefs about mutual violence in relationships. Results highlight the importance of culturally relevant prevention and intervention programs that consider these relationship contexts