Comparison of early-, late-, and non-participants in a school-based asthma management program for urban high school students

<p>Abstract</p> <p>Background</p> <p>To assess bias and generalizability of results in randomized controlled trials (RCT), investigators compare participants to non-participants or early- to late-participants. Comparisons can also inform the recruitment approach, especially when working with challenging populations, such as urban adolescents. In this paper, we describe characteristics by participant status of urban teens eligible to participate in a RCT of a school-based, web-based asthma management program.</p> <p>Methods</p> <p>The denominator for this analysis was all students found to be eligible to participate in the RCT. Data were analyzed for participants and non-participants of the RCT, as well as for students that enrolled during the initially scheduled recruitment period (early-participants) and persons that delayed enrollment until the following fall when recruitment was re-opened to increase sample size (late-participants). Full Time Equivalents (FTEs) of staff associated with recruitment were estimated.</p> <p>Results</p> <p>Of 1668 teens eligible for the RCT, 386 enrolled early, and 36 enrolled late, leaving 1246 non-participants. Participants were younger (p < 0.01), more likely to be diagnosed, use asthma medication, and have moderate-to-severe disease than non-participants, odds ratios (95% Confidence Intervals) = 2.1(1.7-2.8), 1.7(1.3-2.1), 1.4(1.0-1.8), respectively. ORs were elevated for the association of late-participation with Medicaid enrollment, 1.9(0.7-5.1) and extrinsic motivation to enroll, 1.7(0.6-5.0). Late-participation was inversely related to study compliance for teens and caregivers, ORs ranging from 0.1 to 0.3 (all p-values < 0.01). Early- and late-participants required 0.45 FTEs/100 and 3.3 FTEs/100, respectively.</p> <p>Conclusions</p> <p>Recruitment messages attracted youth with moderate-to-severe asthma, but extending enrollment was costly, resulting in potentially less motivated, and certainly less compliant, participants. Investigators must balance internal versus external validity in the decision to extend recruitment. Gains in sample size and external validity may be offset by the cost of additional staff time and the threat to internal validity caused by lower participant follow-up.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00201058">NCT00201058</a></p

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

The transport of Icelandic volcanic ash: insights from northern European cryptotephra records

Fine ash produced during volcanic eruptions can be dispersed over a vast area, where it poses a threat to aviation, human health and infrastructure. We analyse the particle size distributions, geochemistry and glass shard morphology of 19 distal (>1000 km from source) volcanic ash deposits distributed across northern Europe, many geochemically linked to a specific volcanic eruption. The largest glass shards in the cryptotephra deposits were 250 µm (longest axis basis). For the first time, we examine the replicability and reliability of glass shard size measurements from peatland and lake archives. We identify no consistent trend in the vertical sorting of glass shards by size within lake and peat sediments. Measuring the sizes of 100 shards from the vertical sample of peak shard concentration is generally sufficient to ascertain the median shard size for a cryptotephra deposit. Lakes and peatlands in close proximity contain cryptotephras with significantly different median shard size in four out of five instances. The trend toward a greater amount of larger shards in lakes may have implications for the selection of distal sites to constrain the maximum glass shard size for modelling studies. Although the 95th percentile values for shard size generally indicate a loss of larger shards from deposits at sites farther from the volcano, due to the dynamic nature of the controls on tephra transport even during the course of one eruption there is no simple relationship between median shard size and transport distance

'How Poor are you?' - A comparison of four questionnaire delivery modes for assessing socio-economic position in rural Zimbabwe

Assessing socio-economic position can be difficult, particularly in developing countries. Collection of socio-economic data usually relies on interviewer-administered questionnaires, but there is little research exploring how questionnaire delivery mode (QDM) influences reporting of these indicators. This paper reports on results of a trial of four QDMs, and the effect of mode on poverty reporting

Identification of Baicalin as an Immunoregulatory Compound by Controlling TH17 Cell Differentiation

TH17 cells have been implicated in a growing list of inflammatory disorders. Antagonism of TH17 cells can be used for the treatment of inflammatory injury. Currently, very little is known about the natural compound controlling the differentiation of TH17 cells. Here, we showed that Baicalin, a compound isolated from a Chinese herb, inhibited TH17 cell differentiation both in vitro and in vivo. Baicalin might inhibit newly generated TH17 cells via reducing RORγt expression, and together with up-regulating Foxp3 expression to suppress RORγt-mediated IL-17 expression in established TH17 cells. In vivo treatment with Baicalin could inhibit TH17 cell differentiation, restrain TH17 cells infiltration into kidney, and protect MRL/lpr mice against nephritis. Our findings not only demonstrate that Baicalin could control TH17 cell differentiation but also suggest that Baicalin might be a promising therapeutic agent for the treatment of TH17 cells-mediated inflammatory diseases

Towards a model of contemporary parenting: The parenting behaviours and dimensions questionnaire

The assessment of parenting has been problematic due to theoretical disagreement, concerns over generalisability, and problems with the psychometric properties of current parenting measures. The aim of this study was to develop a comprehensive, psychometrically sound self-report parenting measure for use with parents of preadolescent children, and to use this empirical scale development process to identify the core dimensions of contemporary parenting behaviour. Following item generation and parent review, 846 parents completed an online survey comprising 116 parenting items. Exploratory and confirmatory factor analyses supported a six factor parenting model, comprising Emotional Warmth, Punitive Discipline, Anxious Intrusiveness, Autonomy Support, Permissive Discipline and Democratic Discipline. This measure will allow for the comprehensive and consistent assessment of parenting in future research and practice

Long-term breeding phenology shift in royal penguins

The Earth's climate is undergoing rapid warming, unprecedented in recent times, which is driving shifts in the distribution and phenology of many plants and animals. Quantifying changes in breeding phenology is important for understanding how populations respond to these changes. While data on shifts in phenology are common for Northern Hemisphere species (especially birds), there is a dearth of evidence from the Southern Hemisphere, and even fewer data available from the marine environment. Surface air temperatures at Macquarie Island have increased by 0.62°C during the 30-year study period (0.21°C decade−1) and royal penguins (Eudyptes schlegeli) commenced egg laying on average three days earlier in the 1990s than during the 1960s. This contrasts with other studies of Southern Ocean seabirds; five of nine species are now breeding on average 2.1 days later than during the 1950s. Despite the different direction of these trends, they can be explained by a single underlying mechanism: resource availability. There was a negative relationship between the Southern Annular Mode (SAM) and median laying date of royal penguins, such that low-productivity (low SAM) years delayed laying date. This accords with the observations of other seabird species from the Antarctic, where later laying dates were associated with lower sea ice and lower spring productivity. The unifying factor underpinning phenological trends in eastern Antarctica is therefore resource availability; as food becomes scarcer, birds breed later. These changes are not uniform across the region, however, with resource increases in the subantarctic and decreases in eastern Antarctica.Mark A. Hindell, Corey J. A. Bradshaw, Barry W. Brook, Damien A. Fordham, Knowles Kerry, Cindy Hull & Clive R. McMaho