Background. The research proposed herein, is in line with the Swedish Research Council's current focus on International collaborations and postdoctoral work abroad. In this case the child brain and translational and clinical infant brain research. Neonatal hypoxic ischemic encephalopathy in term infants constitutes a serious health problem, not the least due to its often life-long consequences in the form of cerebral palsy and other forms of brain dysfunction.

An estimated 3-5 of every 1000 live term births are affected, a quarter of which with severe symptoms; 10-30% of the affected children do not survive, 30% suffer life-long disabilities \[1-9\]. The incidence may be 10-fold higher in the developing world. In Sweden, an estimated 200 children are born each year with hypoxic ischemic asphyxia or oxygen deprivation during delivery of a severity necessitating treatment, in order to reduce future handicap. Not only the brain, but also other organs, such as the heart, liver or kidney can be damaged by hypoxic ischemia.

In clinical trials, proof has been obtained that cooling can have positive effects counteracting brain injury induced by oxygen deprivation (asphyxia) \[1-7, 9\]. Recent research suggests that cooling may also have a positive effect in stroke (30000 new cases/year in Sweden) during the pre-treatment/transportation to hospital phase.

PCM. A material with phase change properties (PCM) can be a chemical element, a solution or a substance with high melting energy \[10-13\]. It melts/solidifies at a precise temperature and can store considerable amounts of energy (heat) before changing from one phase to another. The study project have used elements or solutions that change between solid and fluid phases within a narrow temperature interval. The most common use of PCM today is for energy storage, accomplished by having the PCM change between solid and fluid phases. Phase changes that include other PCMs, high temperatures and/or gas phases are less useful in medical applications due to the need of either large volumes in a low pressure setting or smaller amounts in a high pressure setting, increasing the risk for mistakes or secondary injury to medical staff or patients. For the clinical purposes of hypothermic treatment described here, the Glauber salt-based PCM in a mattress form developed by the applicant has near ideal properties; it is completely safe, does not cause over-cooling, can be reused many times, eliminates cooling fluctuations, is easy to handle and biodegradable. III. Methods Whole body cooling with PCM mattresses is straightforward. Rectal temperature will be monitored in standard ways. Several other vital parameters, such as LDH in blood, and standard procedures will be used to monitor condition of the infants continuously. 15 days after treatment, MRI will be carried out at the National Hospital of Pediatrics in Hanoi. Follow up of the treated and control children will be carried out at 18 months of age and will be the bases of the final evaluation of the clinical trial.

Design. The project is based on the applicant's dual expertise in engineering and medicine. The applicant developed a key technology, cooling using a special PCM composition, recently. The applicant has also participated in multicenter hypothermia studies of newborn infants (including the TOBY trial). As part of the PhD program, the applicant has also participated in animal research using a large newborn anesthetized piglet therapeutic hypothermia model in collaboration with Dr. Nicola Robertson and her team at University College of London. These experiences enable design of the current project.

Assessment is done continuously during the first 60 minutes. If criteria A and B are fulfilled, treatment is started before 6 hours of life. Amplitude-integrated EEG is not mandatory to start hypothermia treatment. V. Significance The significance of the research project would be to demonstrate that a novel PCM-technology based method, previously not clinically tested, and could be developed all the way to clinical implementation. In infants, the method has the specific advantage of being easily applied already during transport to a hospital, which makes it possible to begin cooling of many children within the current 6 hr. age limit. If hypoxic ischemic encephalopathy can be prevent fully or partly by hypothermia with PCM, major life-long health improvements for many children worldwide, would result. PCM-based cooling is safe, simple, reusable, environmentally safe, non-toxic, and independent of clean water and electricity and a method where the risk of temperature undershooting causing additional damage is eliminated.