Transient but not genetic loss of miR-451 attenuates the development of pulmonary arterial hypertension

<b>Rationale:</b> MicroRNAs are small non-coding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work established that miR-451 is up-regulated in rodent models of PAH.<p></p> <b>Objectives:</b> The role of miR-451 in the pulmonary circulation is unknown. We therefore sought to assess the involvement of miR-451 in the development of pulmonary arterial hypertension.<p></p> <b>Methods:</b> Silencing of miR-451 was performed in vivo using miR-451 knockout mice and an antimiR targeting mature miR-451 in rats. Coupled with exposure to hypoxia, indices of pulmonary arterial hypertension were assessed. The effect of modulating miR-451 on human pulmonary artery smooth muscle cell proliferation and migration was analysed.<p></p> <b>Measurements and Main Results:</b> We observed a reduction in systolic right ventricular pressure in hypoxic rats pre-treated with antimiR-451 compared to hypoxia alone (47.7 ± 1.36mmHg and 56.0 ± 2.03mmHg respectively, p<0.01). In miR-451 knockout mice following exposure to chronic hypoxia, no significant differences were observed compared to wild type hypoxic mice. In vitro analysis demonstrated that over-expression of miR-451 in human pulmonary artery smooth muscle cells promoted migration under serum-free conditions. No effect on cellular proliferation was observed.<p></p> <b>Conclusions:</b> Transient inhibition of miR-451 attenuated the development of pulmonary arterial hypertension in hypoxia exposed rats. Genetic deletion of miR-451 had no beneficial effect on indices of pulmonary arterial hypertension, potentially due to pathway redundancy compensating for the loss of miR-451.<p></p&gt

Analytical solution of the geodesic equation in Kerr-(anti) de Sitter space-times

The complete analytical solutions of the geodesic equations in Kerr-de Sitter and Kerr-anti-de Sitter space-times are presented. They are expressed in terms of Weierstrass elliptic p, zeta, and sigma functions as well as hyperelliptic Kleinian sigma functions restricted to the one-dimensional theta-divisor. We analyze the dependency of timelike geodesics on the parameters of the space-time metric and the test-particle and compare the results with the situation in Kerr space-time with vanishing cosmological constant. Furthermore, we systematically can find all last stable spherical and circular orbits and derive the expressions of the deflection angle of flyby orbits, the orbital frequencies of bound orbits, the periastron shift, and the Lense-Thirring effect.Comment: 18 pages, 11 figure

Risk for self-reported anorexia or bulimia nervosa based on drive for thinness and negative affect clusters/dimensions during adolescence: A three-year prospective study of the TChAD cohort: Drive for Thinness and Negative Affect

The present study explored the cross-sectional and predictive effect of drive for thinness and/or negative affect scores on the development of self-reported anorexia nervosa (AN) and bulimia nervosa (BN)

Prediction of 7-year psychopathology from mother-infant joint attention behaviours: a nested case–control study

<br>Background: To investigate whether later diagnosis of psychiatric disorder can be predicted from analysis of mother-infant joint attention (JA) behaviours in social-communicative interaction at 12 months.</br> <br>Method: Using data from a large contemporary birth cohort, we examined 159 videos of a mother-infant interaction for joint attention behaviour when children were aged one year, sampled from within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Fifty-three of the videos involved infants who were later considered to have a psychiatric disorder at seven years and 106 were same aged controls. Psychopathologies included in the case group were disruptive behaviour disorders, oppositional-conduct disorder, attention-deficit/hyperactivity disorder, pervasive development disorder, anxiety and depressive disorders. Psychiatric diagnoses were obtained using the Development and Wellbeing Assessment when the children were seven years old.</br> <br>Results: None of the three JA behaviours (shared look rate, shared attention rate and shared attention intensity) showed a significant association with the primary outcome of case–control status. Only shared look rate predicted any of the exploratory sub-diagnosis outcomes and was found to be positively associated with later oppositional-conduct disorders (OR [95% CI]: 1.5 [1.0, 2.3]; p = 0.041).</br><br>Conclusions: JA behaviours did not, in general, predict later psychopathology. However, shared look was positively associated with later oppositional-conduct disorders. This suggests that some features of JA may be early markers of later psychopathology. Further investigation will be required to determine whether any JA behaviours can be used to screen for families in need of intervention.</br&gt

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al

Measurement of psychological entitlement in 28 countries

This article presents the cross-cultural validation of the Entitlement Attitudes Questionnaire, a tool designed to measure three facets of psychological entitlement: active, passive, and revenge entitlement. Active entitlement was defined as the tendency to protect individual rights based on self-worthiness. Passive entitlement was defined as the belief in obligations to and expectations toward other people and institutions for the fulfillment of the individual’s needs. Revenge entitlement was defined as the tendency to protect one’s individual rights when violated by others and the tendency to reciprocate insults. The 15-item EAQ was validated in a series of three studies: the first one on a general Polish sample (N = 1,900), the second one on a sample of Polish students (N = 199), and the third one on student samples from 28 countries (N = 5,979). A three-factor solution was confirmed across all samples. Examination of measurement equivalence indicated partial metric invariance of EAQ for all national samples. Discriminant and convergent validity of the EAQ was also confirmed

Investigation of the international comparability of population-based routine hospital data set derived comorbidity scores for patients with lung cancer

Introduction: The International Cancer Benchmarking Partnership (ICBP) identified significant international differences in lung cancer survival. Differing levels of comorbid disease across ICBP countries has been suggested as a potential explanation of this variation but, to date, no studies have quantified its impact. This study investigated whether comparable, robust comorbidity scores can be derived from the different routine population-based cancer data sets available in the ICBP jurisdictions and, if so, use them to quantify international variation in comorbidity and determine its influence on outcome. Methods: Linked population-based lung cancer registry and hospital discharge data sets were acquired from nine ICBP jurisdictions in Australia, Canada, Norway and the UK providing a study population of 233 981 individuals. For each person in this cohort Charlson, Elixhauser and inpatient bed day Comorbidity Scores were derived relating to the 4–36 months prior to their lung cancer diagnosis. The scores were then compared to assess their validity and feasibility of use in international survival comparisons. Results: It was feasible to generate the three comorbidity scores for each jurisdiction, which were found to have good content, face and concurrent validity. Predictive validity was limited and there was evidence that the reliability was questionable. Conclusion: The results presented here indicate that interjurisdictional comparability of recorded comorbidity was limited due to probable differences in coding and hospital admission practices in each area. Before the contribution of comorbidity on international differences in cancer survival can be investigated an internationally harmonised comorbidity index is required