Functional analysis of the Arabidopsis thaliana MUTE promoter reveals a regulatory region sufficient for stomatal-lineage expression.

MAIN CONCLUSION: The MUTE promoter contains a 175-bp region rich in Dof regulatory elements (AAAG) that is necessary and sufficient for initiation of transcription in meristemoids and the stomatal lineage. The molecular mechanism underlying the decision to divide or differentiate is a central question in developmental biology. During stomatal development, expression of the master regulator MUTE triggers the differentiation of meristemoids into stomata. In this study, we carried out MUTE promoter deletion analysis to define a regulatory region that promotes the initiation of expression in meristemoids. Expression constructs with truncated promoter fragments fused to ß-glucuronidase (GUS) were developed. The full-length promoter and promoter truncations of at least 500 bp from the translational start site exhibited normal spatiotemporal expression patterns. Further truncation revealed a 175-bp promoter fragment that was necessary and sufficient for stomatal-lineage expression. Known cis-elements were identified and tested for functional relevance. Comparison of orthologous MUTE promoters suggested DNA binding with one finger (Dof) regulatory elements and novel motifs may be important for regulation. Our data highlight the complexity and combinatorial control of gene regulation and provides tools to further investigate the genetic control of stomatal development.

Advances in growth chart design and use: the UK experience.

As part of the process of adopting the WHO standard in the United Kingdom, the Royal College of Paediatrics and Child Health (RCPCH) was commissioned by the UK Department of Health to design new UK-WHO growth charts. The working group for this project combined expertise ranging from statistics and graphic design to qualitative research, as well as paediatrics, nursing and dietetics. New charts for children under 4 years were published in 2009 and are now widely used in the UK and beyond (www.growthcharts.rcpch.ac.uk). This paper will describe what we have learned in general about the process of designing charts and how these principles were applied to the design of a novel chart designed specifically for sick and premature infants. A successful design first requires clarity about the exact purpose of the chart and who will use it. The layout of the chart can then be varied in many ways to fit that use and ensure users are not misled. Users need consistent and well-evidenced rules for chart use. Drafting the instructions serves as a powerful test of the validity and clarity of the design. However, charts need also to be formally evaluated, as expert views will not reflect those of the average user. The Neonatal and Infant Close Monitoring (NICM) chart included various novel design features, including date boxes for gestational age adjustment and low SD lines to help assess very small infants. It was evaluated at three stages using plotting exercises and each phase led to substantial design changes. Growth charts are conceptually very complex, with the capacity to mislead as well as inform and should always be formally evaluated before implementation.

Setting research priorities to reduce global mortality from preterm birth and low birth weight by 2015.

AIM: This paper aims to identify health research priorities that could improve the rate of progress in reducing global neonatal mortality from preterm birth and low birth weight (PB/LBW), as set out in the UN's Millennium Development Goal 4. METHODS: We applied the Child Health and Nutrition Research Initiative (CHNRI) methodology for setting priorities in health research investments. In the process coordinated by the World Health Organization in 2007-2008, 21 researchers with interest in child, maternal and newborn health suggested 82 research ideas that spanned across the broad spectrum of epidemiological research, health policy and systems research, improvement of existing interventions and development of new interventions. The 82 research questions were then assessed for answerability, effectiveness, deliverability, maximum potential for mortality reduction and the effect on equity using the CHNRI method. RESULTS: The top 10 identified research priorities were dominated by health systems and policy research questions (eg, identification of LBW infants born at home within 24-48 hours of birth for additional care; approaches to improve quality of care of LBW infants in health facilities; identification of barriers to optimal home care practices including care seeking; and approaches to increase the use of antenatal corticosteriods in preterm labor and to improve access to hospital care for LBW infants). These were followed by priorities for improvement of the existing interventions (eg, early initiation of breastfeeding, including feeding mode and techniques for those unable to suckle directly from the breast; improved cord care, such as chlorhexidine application; and alternative methods to Kangaroo Mother Care (KMC) to keep LBW infants warm in community settings). The highest-ranked epidemiological question suggested improving criteria for identifying LBW infants who need to be cared for in a hospital. Among the new interventions, the greatest support was shown for the development of new simple and effective interventions for providing thermal care to LBW infants, if KMC is not acceptable to the mother. CONCLUSION: The context for this exercise was set within the MDG4, requiring an urgent and rapid progress in mortality reduction from low birth weight, rather than identifying long-term strategic solutions of the greatest potential. In a short-term context, the health policy and systems research to improve access and coverage by the existing interventions, coupled with further research to improve effectiveness, deliverability and acceptance of existing interventions, and epidemiological research to address the key gaps in knowledge, were all highlighted as research priorities.

Designing the new UK-WHO growth charts to enhance assessment of growth around birth.

The decision to adopt the new WHO standard in the UK necessitated substantial changes to the neonatal section of the chart, including separation of the preterm UK birth weight reference from the WHO standard. The evidence-based design process has led to several novel features that could be generally applied in other chart designs, and revealed uncertainties leading to inconsistencies in charting. Failing to plot the birth weight of term infants at age 0 can lead to spurious centile crossing in the early weeks of life, particularly among infants at the extreme of gestation. Users will need training to use the charts, but this should improve overall understanding and the use of charts.

Monitoring head size and growth using the new UK-WHO growth standard.

In order to assess the extent to which children in the UK will follow the UK-WHO head circumference standard, the authors used head circumference data from the Southampton Women's Survey (n=3159) and the Avon Longitudinal Study of Parents and Children (n=15 208) in children aged 0-36 months, converted into z-scores using both the UK-WHO and UK1990 references. Rapid head growth was defined as crossing upwards through two major centile bands (1.33 SD). The UK-WHO standard identified many more infants with heads above the 98th centile than to the UK1990 reference (UK-WHO: 6-16% of infants at various ages; UK1990: 1-4%). Rapid head growth in the first 6-9 months was also much more common using the UK-WHO standard (UK-WHO: 14.6-15.3%; UK1990: 4.8-5.1%). Practitioners should be aware of these findings to avoid unnecessary referrals.

Revised birth centiles for weight, length and head circumference in the UK-WHO growth charts.

BACKGROUND: The adoption in May 2009 by the UK of the WHO 2006 standard necessitated the provision of UK-based birth centiles for pre-term infants. The pre-existing British 1990 reference birth centiles, used in the UK since 1995, had been biased by the inclusion of post-natal data. AIM: To describe the construction of new UK birth centiles for weight, length and head circumference, based on British 1990 reference data, but excluding post-natal data. SUBJECTS AND METHODS: Birth data from the five original studies, collected between 1983-1993, were pooled and analysed by the LMS method, for the sexes separately. In addition, sex-specific composite centiles were constructed for infants born at term (37-42 completed weeks). RESULTS: The birth data included 9443 weights, 985 lengths and 1841 head circumferences, covering 23-44 weeks gestation. The analysis provided LMS tables defining reference centiles for weight and head circumference from 23-42 weeks and for length from 26-42 weeks. The term centiles are for use at age 0 on the post-natal 0-1 year chart. CONCLUSION: These new centiles, replacing those of the British 1990 reference, are more accurate than their predecessors which were biased due to the inclusion of post-natal data.

Economic evaluation of enhanced staff contact for the promotion of breastfeeding for low birth weight infants.

OBJECTIVES: There is evidence that breastmilk feeding reduces mortality and short and long-term morbidity among infants born too soon or too small. The aim of this study was to evaluate the cost-effectiveness of enhanced staff contact for mothers with infants in a neonatal unit with a birth weight of 500-2,500 g from the perspective of the UK National Health Service. METHODS: A decision-tree model linked clinical outcomes with long-term health outcomes. The study population was divided into three weight bands: 500-999 g, 1000-1,749 g, and 1,750-2,500 g. Clinical and resource use data were obtained from literature reviews. The measure of benefit was quality-adjusted life-years. Uncertainty was evaluated using cost-effectiveness acceptability curves and sensitivity analyses. RESULTS: The intervention was less costly and more effective than the comparator in the base-case analysis for each birth weight group. The results were quite robust to the sensitivity analyses performed. CONCLUSIONS: This is the first economic evaluation in this complex field and offers a model to be developed in future research. The results provide preliminary indications that enhanced staff contact may be cost-effective. However, the limited evidence available, and the limited UK data in particular, suggest that further research is required to provide results with confidence.