Quantification of Hox and Surfactant Protein-B Transcription during Murine Lung Development.

Abstract BACKGROUND: Genetic processes underlying fetal lung development and maturation are incompletely understood. Better knowledge of these processes would provide insights into the causes of lung malformations and prevention of respiratory distress syndrome and the potential adverse effects of glucocorticoids. Hox genes are involved in the lung branching morphogenesis and maturation of respiratory epithelium, but their expression pattern remains to be defined. OBJECTIVES: We hypothesized that genes involved in lung branching would be downregulated during early development, whereas those involved in maturation would be unchanged or upregulated. METHODS: TaqMan real-time primers and probes were designed for all 39 murine Hox genes, and the murine SP-B gene and transcription profiles of these genes were obtained from whole lungs isolated at e14.5, e16.5, e18.5, e19.5 and postnatal days 1 and 20. RESULTS: Hox genes in clusters A and B, specifically those between paralog groups 3 and 7, were the most represented, with Hoxa4 and Hoxa5 being the most highly transcribed. A wave of reduced transcription in 16 Hox genes, coincident with increased SP-B transcription, was observed with advancing gestation. Consistently high transcription of Hoxa5 from e14.5 to postnatal day 20 may indicate that sustained transcription is required for normal lung maturation. When e15.5 lungs were cultured with dexamethasone, Hoxb6, Hoxb7 and Hoxb8 levels were significantly upregulated, creating the potential for modulation of diverse downstream target genes. CONCLUSIONS: Improved understanding of the genetic processes underlying lung development afforded by our Q-PCR platform may allow development of more specific methods for inducing fetal lung maturation.

The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.:the results of the LRF AML14 trial

The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.

Fathers’ Views and Understanding of their Roles in Families with a Child with Acute Lymphoblastic Leukaemia: An Interpretative Phenomenological Analysis

This study explored how fathers of children diagnosed with acute lymphoblastic leukaemia (ALL) perceived and understood the roles they had within their family over the course of their child’s illness and treatment. In-depth semi-structured interviews were conducted with five fathers. Transcripts were analysed using interpretative phenomenological analysis (IPA). The major themes that emerged were: adjusting to the diagnosis; the experience of maternal gate-keeping; striving for normalization; experiences of giving and receiving support. Overall, the fathers perceived themselves as having significant responsibility in helping their child and family cope with the illness experience. Clinical implications, including the need for professionals to recognize and more openly acknowledge the father’s position, are considered.

Child Welfare Interventions: Patterns of Social Work Practice

Some 10 years ago one of the authors embarked on a research study examining the potential for social workers to shift from a child protection to a child welfare practice orientation (Spratt, 2000; 2001; Spratt and Callan, 2004). The research reported here develops that work; examining how social workers respond to ‘child care problems’ (CCPs). The results indicate that Northern Irish Health and Social Services Trusts (equivalent to Local Authorities in England and Wales) have responded to social policy goals to balance the protection of a lesser number of children whilst meeting the welfare needs of the greater by reducing the number of referrals designated ‘child protection investigations’ (CPIs) and increasing the number of CCPs. Closer analysis reveals, however, that a filtering system has been developed by social workers to address perceived child protection risks within CCP cases. Paradoxically, this leads to early closure of the more concerning cases, with service provision largely confined to the least concerning. The authors argue that the ways in which social workers balance social policing and supportive functions in practice may indicate possible responses to an increase in referred families anticipated within Every Child Matters (Chief Secretary to the Treasury, 2003).

An Innovative Model for the Provision of Practice Learning Opportunities in Family and Child Care: Newry Student Unit, Southern Health and Social Care Trust.

This article describes the work of Newry Student Unit which operates in the Southern Health and Social Care Trust. The background to the unit is outlined and its development is discussed in the context of practice learning provision in Northern Ireland. The operation of the unit in providing Family and Child Care practice learning opportunities (PLOs) for student social workers is outlined and findings from evaluation questionnaires completed by students, college tutors and team leaders are presented. The paper highlights both the advantages and disadvantages of this model of PLO provision and concludes that it is a valuable resource for practice learning. Proposals for the development of the unit are discussed and it is suggested that the model has the potential be replicated in other areas of Northern Ireland.

Imaging the future: theatre and change within the child protection system

The use of social pedagogy as a paradigm for critically appraising developments within child and family social work has been largely neglected. This paper outlines the work of Augusto Boal and his adoption of social pedagogy as a method for empowering oppres-sed social groups in Brazil. It is argued that Boal’s approach can be adapted by using action research techniques to analyse and effect change in situations where child care professionals face daily contradictions in their attempts to both protect children and support families. To demonstrate its relevance to child care practice, a description is provided of how the approach was used with two groups of social work students – one undertaking qualifying training, the other post-qualifying training. The results of this application suggest a new theoretical framework for practice which aims to establish communicative consensus around the needs of children and a mutual appreciation of roles and responsibilities.