Epithelial sodium channel in airway epithelium of the newborn infant : Implications for postnatal pulmonary adaptation

The aim of the present thesis was to study the role of the epithelial sodium channel (ENaC) in clearance of fetal lung fluid in the newborn infant by measurement of airway epithelial expression of ENaC, of nasal transepithelial potential difference (N-PD), and of lung compliance (LC). In addition, the effect of postnatal dexamethasone on airway epithelial ENaC expression was measured in preterm infants with bronchopulmonary dysplasia (BPD). The patient population was formed of selected term newborn infants born in the Department of Obstetrics (Studies II-IV) and selected preterm newborn infants treated in the neonatal intensive care unit of the Hospital for Children and Adolescents (Studies I and IV) of the Helsinki University Central Hospital in Finland. A small population of preterm infants suffering from BPD was included in Study I. Studies I, III, and IV included airway epithelial measurement of ENaC and in Studies II and III, measurement of N-PD and LC. In Study I, ENaC expression analyses were performed in the Research Institute of the Hospital for Sick Children in Toronto, Ontario, Canada. In the following studies, analyses were performed in the Scientific Laboratory of the Hospital for Children and Adolescents. N-PD and LC measurements were performed at bedside in these hospitals. In term newborn infants, the percentage of amiloride-sensitive N-PD, a surrogate for ENaC activity, measured during the first 4 postnatal hours correlates positively with LC measured 1 to 2 days postnatally. Preterm infants with BPD had, after a therapeutic dose of dexamethasone, higher airway epithelial ENaC expression than before treatment. These patients were subsequently weaned from mechanical ventilation, probably as a result of the clearance of extra fluid from the alveolar spaces. In addition, we found that in preterm infants ENaC expression increases with gestational age (GA). In preterm infants, ENaC expression in the airway epithelium was lower than in term newborn infants. During the early postnatal period in those born both preterm and term airway epithelial βENaC expression decreased significantly. Term newborn infants delivered vaginally had a significantly smaller airway epithelial expression of αENaC after the first postnatal day than did those delivered by cesarean section. The functional studies showed no difference in N-PD between infants delivered vaginally and by cesarean section. We therefore conclude that the low airway epithelial expression of ENaC in the preterm infant and the correlation of N-PD with LC in the term infant indicate a role for ENaC in the pathogenesis of perinatal pulmonary adaptation and neonatal respiratory distress. Because dexamethasone raised ENaC expression in preterm infants with BPD, and infants were subsequently weaned from ventilator therapy, we suggest that studies on the treatment of respiratory distress in the preterm infant should include the induction of ENaC activity.

The Effect of Intrauterine Growth Restriction on Long-Term Outcome in Very or Extremely Low Birth Weight Infants

The project consisted of two long-term follow-up studies of preterm children addressing the question whether intrauterine growth restriction affects the outcome. Assessment at 5 years of age of 203 children with a birth weight less than 1000 g born in Finland in 1996-1997 showed that 9% of the children had cognitive impairment, 14% cerebral palsy, and 4% needed a hearing aid. The intelligence quotient was lower (p<0.05) than the reference value. Thus, 20% exhibited major, 19% minor disabilities, and 61% had no functional abnormalities. Being small for gestational age (SGA) was associated with sub-optimal growth later. In children born before 27 gestational weeks, the SGA had more neuropsychological disabilities than those appropriate for gestational age (AGA). In another cohort with birth weight less than 1500 g assessed at 5 years of age, echocardiography showed a thickened interventricular septum and a decreased left ventricular end-diastolic diameter in both SGA and AGA born children. They also had a higher systolic blood pressure than the reference. Laser-Doppler flowmetry showed different endothelium-dependent and -independent vasodilation responses in the AGA children compared to those of the controls. SGA was not associated with cardio-vascular abnormalities. Auditory event-related potentials (AERPs) were recorded using an oddball paradigm with frequency deviants (standard tone 500 Hz and deviant 750-Hz with 10% probability). At term, the P350 was smaller in SGA and AGA infants than in controls. At 12 months, the automatic change detection peak (mismatch negativity, MMN) was observed in the controls. However, the pre-term infants had a difference positivity that correlated with their neurodevelopment scores. At 5 years of age, the P1-deflection, which reflects primary auditory processing, was smaller, and the MMN larger in the preterm than in the control children. Even with a challenging paradigm or a distraction paradigm, P1 was smaller in the preterm than in the control children. The SGA and AGA children showed similar AERP responses. Prematurity is a major risk factor for abnormal brain development. Preterm children showed signs of cardiovascular abnormality suggesting that prematurity per se may carry a risk for later morbidity. The small positive amplitudes in AERPs suggest persisting altered auditory processing in the preterm in-fants.

Organisation Carescapes: Researching Organisations, Work and Care

This working paper develops an approach to the analysis of care as it is evident in the policies and practices of employing organisations. We identify how notions of care are incorporated in myriad and multi-faceted ways that may support, survey and control workers, as well as having implications for employers, managers, employees and workers. Aspects of care can be found in a range of statutory duties, policies and related activities, including: health and safety, equality and diversity, parental leave, religious observance, bullying and harassment, personal development, voluntary redundancy, early retirement, employer pension schemes, grievance procedures, and dismissal. The conceptual framework of organisation carescapes is offered as an aid to the analysis of employee policies and services. These policies and services are transformed by shifts in supranational and national policies such as European Union (EU) economic strategies and national legislation on disability rights legislation, age discrimination and flexible working, and changes in labour market competitiveness. In conclusion, we consider how the framework of organisation carescapes is informing research design in our and our colleagues’ ongoing programme of research.

The Quest for Well-being in Growth Industries: Contexts, Research Design and Methodological Development

This Working Paper reports the background to the first stage of the ongoing research project, The Quest for Well-being in Growth Industries: A Collaborative Study in Finland and Scotland, conducted under the auspices of the Academy of Finland research programme The Future of Work and Well-being (2008-2011). This collaborative project provides national and transnational data, analysis and outputs. The study is being conducted in the Department of Management and Organisation, Hanken School of Economics, Finland, in collaboration with Glasgow Caledonian University, University of East London, Heriot-Watt University and Reading University, UK. The project examines policies and practices towards the enhancement of work-related well-being in growth industries, and contradictory pressures and tensions posed in this situation. The overall aim is to evaluate the development, implementation and use of work-related well-being policies in four selected growth industries. These sectors – electronics, care, finance and accounting, and tourism – have been selected on the basis of European Union and national forecasts, and demographic and socio-economic trends in employment. In this working paper we outline the background to the research study, the initial research plan, and how the survey of employers has been constructed. The working paper concludes with a brief discussion of general ongoing research issues arising in the project.

Tree mortality, fire scar formation and regeneration 8 years after low-intensity fire in managed Pinus sylvestris stands

Fire is an important driver of the boreal forest ecosystem, and a useful tool for the restoration of degraded forests. However, we lack knowledge on the ecological processes initiated by prescribed fires, and whether they bring about the desired restoration effects. The purpose of this study was to investigate the impacts of low-intensity experimental prescribed fires on four ecological processes in young commercial Scots pine (Pinus sylvestris) stands eight years after the burning. The processes of interest were tree mortality, dead wood creation, regeneration and fire scar formation. These were inventoried in twelve study plots, which were 30 m x 30 m in size. The plots belonged to two different stand age classes: 30-35 years or 45 years old at the time of burning. The study was partly a follow-up of study plots researched by Sidoroff et al. (2007) one year after burning in 2003. Tree mortality increased from 183 stems ha-1 in 2003 to 259 stems ha-1 in 2010, corresponding to 15 % and 21 % of stem number respectively. Most mortality was experienced in the stands of the younger age class, in smaller diameter classes and among species other than Scots pine. By 2010, the average mortality of Scots pine per plot was 18%, but varied greatly ranging from 0% to 63% of stem number. Delayed mortality, i.e. mortality that occurred between 2 and 8 years after fire, seemed to become more important with increasing diameter. The input of dead wood also varied greatly between plots, from none to 72 m3 ha-1, averaging at 12 m3 ha-1. The amount of fire scarred trees per plot ranged from none to 20 %. Four out of twelve plots (43 %) did not have any fire scars. Scars were on average small: 95% of scars were less than 4 cm in width, and 75% less than 40 cm in length. Owing to the light nature of the fire, the remaining overstorey and thick organic layer, regeneration was poor overall. The abundance of pine and other seedlings indicated a viable seed source existed, but the seedlings failed to establish under dense canopy. The number of saplings ranged from 0 to 12 333 stems ha-1. The results of this study indicate that a low intensity fire does not necessarily initiate the ecological processes of tree mortality, dead wood creation and regeneration in the desired scale. Fire scars, which form the basis of fire dating in fire history studies, did not form in all cases.