RiboSys, a high-resolution, quantitative approach to measure the in vivo kinetics of pre-mRNA splicing and 3'-end processing in Saccharomyces cerevisiae

We describe methods for obtaining a quantitative description of RNA processing at high resolution in budding yeast. As a model gene expression system, we constructed tetON (for induction studies) and tetOFF (for repression, derepression, and RNA degradation studies) yeast strains with a series of reporter genes integrated in the genome under the control of a tetO7 promoter. Reverse transcription and quantitative real-time-PCR (RT-qPCR) methods were adapted to allow the determination of mRNA abundance as the average number of copies per cell in a population. Fluorescence in situ hybridization (FISH) measurements of transcript numbers in individual cells validated the RT-qPCR approach for the average copy-number determination despite the broad distribution of transcript levels within a population of cells. In addition, RT-qPCR was used to distinguish the products of the different steps in splicing of the reporter transcripts, and methods were developed to map and quantify 3′-end cleavage and polyadenylation. This system permits pre-mRNA production, splicing, 3′-end maturation and degradation to be quantitatively monitored with unprecedented kinetic detail, suitable for mathematical modeling. Using this approach, we demonstrate that reporter transcripts are spliced prior to their 3′-end cleavage and polyadenylation, that is, cotranscriptionally.

Health literacy : what is it and why is it important to measure?

This report summarizes the proceedings of the first Outcome Measures in Rheumatology Clinical Trials (OMERACT) Health Literacy Special Interest Group workshop at the OMERACT 10 conference. Health literacy refers to an individual’s capacity to seek, understand, and use health information. Discussion centered on the relevance of health literacy to the rheumatology field; whether measures of health literacy were important in the context of clinical trials and routine care; and, if so, whether disease-specific measures were required. A nominal group process involving 27 workshop participants, comprising a patient group (n = 12) and a healthcare professional and researcher group (n = 15), confirmed that health literacy encompasses a broad range of concepts and skills that existing scales do not measure. It identified the importance and relevance of patient abilities and characteristics, but also health professional factors and broader contextual factors. Sixteen themes were identified: access to information; cognitive capacity; disease; expression/communication; finances; health professionals; health system; information; literacy/numeracy; management skills; medication; patient approach; dealing with problems; psychological characteristics; social supports; and time. Each of these was divided further into subthemes of one or more of the following: knowledge, attitude, attribute, relationship, skill, action, or context. There were virtually no musculoskeletal-specific statements, suggesting that a generic health literacy tool in rheumatology is justified. The detailed concepts across themes provided new and systematic insight into what needs to be done to improve health literacy and consequently reduce health inequalities. These data will be used to derive a more comprehensive measure of health literacy.

Patient perspective workshop : moving towards OMERACT guidelines for choosing or developing instruments to measure patient-reported outcomes

The workshop Choosing or Developing Instruments held at the Outcome Measures in Rheumatology (OMERACT) 10 meeting was designed to help participants think about the underlying methods of instrument development. Conference pre-reading material and 3 brief introductory presentations elaborated the issues, and participants broke into discussion groups before reconvening to share insights, engage in a more general discussion of the issues, and vote on recommendations. Trade offs between using current imperfect measures and the long and complex process of developing new instruments were considered, together with the need for rigor in patient-reported outcome (PRO) instrument development. The main considerations for PRO instrument development were listed and a research agenda for action produced. As part of the agenda for action, it is recommended that researchers and patient partners work together to tackle these issues, and that OMERACT bring forward proposals for acceptable instrument development protocols that would meet an enhanced “Truth” statement in the OMERACT Filter.

Pensions as well as postcodes : new SES measure

Centrelink information, as well as postcodes, will determine student SES for the purposes of the new equity loading – but only as an interim measure.

Measure for measure

Any new measure of SES needs to have the confidence of the sector and is fit for purpose, writes Trevor Gale.

Development of a multi-dimensional measure of resilience in adolescents : the adolescent resilience questionnaire

Background: The concept of resilience has captured the imagination of researchers and policy makers over the past two decades. However, despite the ever growing body of resilience research, there is a paucity of relevant, comprehensive measurement tools. In this article, the development of a theoretically based, comprehensive multidimensional measure of resilience in adolescents is described.

Methods: Extensive literature review and focus groups with young people living with chronic illness informed the conceptual development of scales and items. Two sequential rounds of factor and scale analyses were undertaken to revise the conceptually developed scales using data collected from young people living with a chronic illness and a general population sample.

Results: The revised Adolescent Resilience Questionnaire comprises 93 items and 12 scales measuring resilience factors in the domains of self, family, peer, school and community. All scales have acceptable alpha coefficients. Revised scales closely reflect conceptually developed scales.

Conclusions: It is proposed that, with further psychometric testing, this new measure of resilience will provide researchers and clinicians with a comprehensive and developmentally appropriate instrument to measure a young person’s capacity to achieve positive outcomes despite life stressors.

Socioeconomic variation in diet and activity-related behaviours of Australian children and adolescents aged 2–16 years

Background

Evidence for age-related variation in the relationship between obesity-related behaviours and socioeconomic position may assist in the targeting of dietary and physical activity interventions among children.
Objective

To investigate the relationship between different indicators of socioeconomic position and obesity-related behaviours across childhood and adolescence.
Methods

Data were from 4487 children aged 2 to 16 years participating in the cross-sectional 2007 Australian National Children's Nutrition and Physical Activity Survey. Socioeconomic position was defined by the highest education of the primary or secondary carer and parental income. Activity was assessed using recall methods with physical activity also assessed using pedometers. Intake of energy-dense drinks and snack foods, fruits and vegetables was assessed using 2 × 24-h dietary recalls.
Results

A socioeconomic gradient was evident for each dietary measure (although in age-specific analyses, not for energy-dense snacks in older children), as well as television viewing, but not physical activity. Whether each behaviour was most strongly related to parental income or education of the primary or secondary carer was age and sex dependent. The socioeconomic gradient was strongest for television viewing time and consumption of fruit and energy-dense drinks.
Conclusions

A strong socioeconomic gradient in eating behaviours and television viewing time was observed. Relationships for particular behaviours differed by age, sex and how socioeconomic position was defined. Socioeconomic indicators define different population groups and represent different components of socioeconomic position. These findings may provide insights into who should be targeted in preventive health efforts at different life stages.

Bowel cancer screening : how do we measure success?

A key part of monitoring and evaluating any health intervention is to define what constitutes success for that intervention and how we would measure whether or not the intervention has achieved this success. This presentation will present an overview of the objectives of the National Bowel Screening Program and what data are needed to monitor the program’s success in meeting these objectives.

Framingham risk prediction equations for incidence of cardiovascular disease using detailed measures for smoking

Current prediction models for risk of cardiovascular disease (CVD) incidence incorporate smoking as a dichotomous yes/no measure. However, the risk of CVD associated with smoking also varies with the intensity and duration of smoking and there is a strong association between time since quitting and the risk of disease onset. This study aims to develop improved risk prediction equations for CVD incidence incorporating intensity and duration of smoking and time since quitting. The risk of developing a first CVD event was evaluated using a Cox’s model for participants in the Framingham offspring cohort who attended the fourth examination (1988–92) between the ages of 30 and 74 years and were free of CVD (n=3751). The full models based on the smoking variables and other risk factors, and reduced models based on the smoking variables and non-laboratory risk factors demonstrated good discrimination, calibration and global fit. The incorporation of both time since quitting among past smokers and pack-years among current smokers resulted in better predictive performance as compared to a dichotomous current/non-smoker measure and a current/quitter/never smoker measure. Compared to never smokers, the risk of CVD incidence increased with pack-years. Risk among those quitting more than five years prior to the baseline exam and within five years prior to the baseline exam were similar and twice as high as that of never smokers. A CVD risk equation incorporating the effects of pack-years and time since quitting provides an improved tool to quantify risk and guide preventive care.