Exaggerated elastin turnover in young individuals with Marfan Syndrome – new insights from the AIMS trial

Background and aims: The fragmentation and loss of elastic fibre in the tunica media of the aorta is a pathological hallmark of Marfan syndrome (MFS) but the dynamics of elastin degradation and its relationship to aortic size and physiological growth remain poorly understood.Methods: In this post-hoc analysis of the AIMS randomised-controlled trial, the association of plasma desmosine (pDES) - a specific biomarker of mature elastin degradation - with age and aortic size was analysed in 113 patients with MFS and compared to 109 healthy controls.Results: There was a strong association between age and pDES in both groups, with higher pDES levels in the lower age groups compared to adults. During childhood, pDES increased and peaked during early adolescence, and thereafter decreased to lower adult levels. This trend was exaggerated in young individuals with MFS but in those above 25 years of age, pDES levels were comparable to controls despite the presence of aortic root dilation. In MFS children, increased aortic diameter relative to controls was seen at an early age and although the increase in diameter was less after adolescence, aortic root size continued to increase steadily with age. In MFS participants there was an indication of a positive association between baseline pDES levels and aortic root dilatation during up to 5 years of follow up.Conclusion: This study has shown that developmental age has a significant effect on levels of elastin turnover as measured by pDES in MFS individuals as well as healthy controls. This effect is exaggerated in those with MFS with increased levels seen during the period of physiologic development which plateaus towards adulthood. This suggests an early onset of pathophysiology that may present an important opportunity for disease modifying intervention

FICTION-TSA analysis of the B-cell compartment in myeloma shows no significant expansion of myeloma precursor cells

Faith E. Davies, Andrew C. Rawstron, Guy Pratt, Sheila O'Connor, Lela Su'ut, David Blythe, James Fenton, David Claydon, J. Anthony Child, Andrew S. Jack & Gareth J. Morga

Miller Early Childhood Sustained Home-visiting (MECSH) trial: design, method and sample description

<p>Abstract</p> <p>Background</p> <p>Home visiting programs comprising intensive and sustained visits by professionals (usually nurses) over the first two years of life show promise in promoting child health and family functioning, and ameliorating disadvantage. Australian evidence of the effectiveness of sustained nurse home visiting in early childhood is limited. This paper describes the method and cohort characteristics of the first Australian study of sustained home visiting commencing antenatally and continuing to child-age two years for at-risk mothers in a disadvantaged community (the Miller Early Childhood Sustained Home-visiting trial).</p> <p>Methods and design</p> <p>Mothers reporting risks for poorer parenting outcomes residing in an area of socioeconomic disadvantage were recruited between February 2003 and March 2005. Mothers randomised to the intervention group received a standardised program of nurse home visiting. Interviews and observations covering child, maternal, family and environmental issues were undertaken with mothers antenatally and at 1, 12 and 24 months postpartum. Standardised tests of child development and maternal-child interaction were undertaken at 18 and 30 months postpartum. Information from hospital and community heath records was also obtained.</p> <p>Discussion</p> <p>A total of 338 women were identified and invited to participate, and 208 were recruited to the study. Rates of active follow-up were 86% at 12 months, 74% at 24 months and 63% at 30 months postpartum. Participation in particular data points ranged from 66% at 1 month to 51% at 24 months postpartum. Rates of active follow-up and data point participation were not significantly different for the intervention or comparison group at any data point. Mothers who presented for antenatal care prior to 20 weeks pregnant, those with household income from full-time employment and those who reported being abused themselves as a child were more likely to be retained in the study. The Miller Early Childhood Sustained Home-visiting trial will provide Australian evidence of the effectiveness of sustained nurse home visiting for children at risk of poorer health and developmental outcomes.</p> <p>Trial registration</p> <p>ACTRN12608000473369</p

Does student loan debt deter higher education participation? New evidence from England

Research among prospective UK undergraduates in 2002 found that some students, especially from low social classes, were deterred from applying to university because of fear of debt. This paper investigates whether this is still the case today in England despite the changing higher education landscape since 2002. The paper describes findings from a 2015 survey of prospective undergraduates and compares them with those from the 2002 study. We find that students’ attitudes to taking on student loan debt are more favorable in 2015 than in 2002. Debt averse attitudes remain much stronger among lower-class students than among upper-class students, and more so than in 2002. However, lower-class students did not have stronger debt averse attitudes than middle-class students. Debt averse attitudes seem more likely to deter planned higher education participation among lower-class students in 2015 than in 2002

Baseline hospital performance and the impact of medical emergency teams: Modelling vs. conventional subgroup analysis

<p>Abstract</p> <p>Background</p> <p>To compare two approaches to the statistical analysis of the relationship between the baseline incidence of adverse events and the effect of medical emergency teams (METs).</p> <p>Methods</p> <p>Using data from a cluster randomized controlled trial (the MERIT study), we analysed the relationship between the baseline incidence of adverse events and its change from baseline to the MET activation phase using quadratic modelling techniques. We compared the findings with those obtained with conventional subgroup analysis.</p> <p>Results</p> <p>Using linear and quadratic modelling techniques, we found that each unit increase in the baseline incidence of adverse events in MET hospitals was associated with a 0.59 unit subsequent reduction in adverse events (95%CI: 0.33 to 0.86) after MET implementation and activation. This applied to cardiac arrests (0.74; 95%CI: 0.52 to 0.95), unplanned ICU admissions (0.56; 95%CI: 0.26 to 0.85) and unexpected deaths (0.68; 95%CI: 0.45 to 0.90). Control hospitals showed a similar reduction only for cardiac arrests (0.95; 95%CI: 0.56 to 1.32). Comparison using conventional subgroup analysis, on the other hand, detected no significant difference between MET and control hospitals.</p> <p>Conclusions</p> <p>Our study showed that, in the MERIT study, when there was dependence of treatment effect on baseline performance, an approach based on regression modelling helped illustrate the nature and magnitude of such dependence while sub-group analysis did not. The ability to assess the nature and magnitude of such dependence may have policy implications. Regression technique may thus prove useful in analysing data when there is a conditional treatment effect.</p

“You ain’t gonna get away wit’ this, Django”: Fantasy, fiction and subversion in Quentin Tarantino’s, Django Unchained

From 2009 to 2015, U.S. director, Quentin Tarantino, released three films that were notable for their focus on particular historical events, periods and individuals (Inglorious Basterds 2009; Django Unchained 2012; The Hateful Eight 2015). Together, these films offered a specifically “Tarantinian” rendering of history: rewriting, manipulating and, for some, unethically deploying history for aesthetic effect. With regard to Django Unchained, this article examines how Tarantino’s historical revisionism provides a valuable point of inquiry into the ways in which “history” is depicted on-screen and, more importantly, how depictions of “the past” can prove useful for highlighting underlying contradictions, ambivalences and ambiguities in the “present”. Drawing upon Slavoj Žižek’s Lacanian approach to film analysis, it is argued that through a combination of fantasy, subversion and counterfactual possibility – most notable in the film’s final stand-off between its leading black characters – Tarantino is able to render the Real of U.S. slavery as an ahistorical antagonism. This antagonism highlights the ongoing trauma of these events in the present as well as the use of fantasy to explore their traumatic subject matter. Such historical fictions are not fixed to the past but, via an encounter with the Real, can be used to appraise the present