Objective To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE). Study design We enrolled infants in the Intensive Care Nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to four doses adjusted for volume and RBC content,1 – 5 × 107cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post- infusion vital signs. As exploratory analyses we compared cell recipients’ hospital outcomes (mortality, oral feeds at discharge) and one year survival with Bayley III scores ≥ 85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells. Results Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 milliliters. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1 year outcomes survived with scores ≥ 85. Conclusions Collection, preparation and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.

IMPORTANCE Hypothermia at 33.5°C for 72 hours for neonatal hypoxic ischemic encephalopathy reduces death or disability to 44% to 55%; longer cooling and deeper cooling are neuroprotective in animal models. OBJECTIVE To determine if longer duration cooling (120 hours), deeper cooling (32.0°C), or both are superior to cooling at 33.5°C for 72 hours in neonates who are full-term with moderate or severe hypoxic ischemic encephalopathy. DESIGN, SETTING, AND PARTICIPANTS Arandomized, 2 × 2 factorial design clinical trial performed in 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network between October 2010 and November 2013. INTERVENTIONS Neonates were assigned to 4 hypothermia groups; 33.5°C for 72 hours, 32.0°C for 72 hours, 33.5°C for 120 hours, and 32.0°C for 120 hours. MAIN OUTCOMES AND MEASURES The primary outcome of death or disability at 18 to 22 months is ongoing. The independent data and safety monitoring committee paused the trial to evaluate safety (cardiac arrhythmia, persistent acidosis, major vessel thrombosis and bleeding, and death in the neonatal intensive care unit [NICU]) after the first 50 neonates were enrolled, then after every subsequent 25 neonates. The trial was closed for emerging safety profile and futility analysis after the eighth review with 364 neonates enrolled (of 726 planned). This report focuses on safety and NICU deaths by marginal comparisons of 72 hours’ vs 120 hours’ duration and 33.5°C depth vs 32.0°C depth (predefined secondary outcomes). RESULTS The NICU death rates were 7 of 95 neonates (7%) for the 33.5°C for 72 hours group, 13 of 90 neonates (14%) for the 32.0°C for 72 hours group, 15 of 96 neonates (16%) for the 33.5°C for 120 hours group, and 14 of 83 neonates (17%) for the 32.0°C for 120 hours group. The adjusted risk ratio (RR) for NICU deaths for the 120 hours group vs 72 hours group was 1.37 (95% CI, 0.92–2.04) and for the 32.0°C group vs 33.5°C group was 1.24 (95% CI, 0.69–2.25). Safety outcomes were similar between the 120 hours group vs 72 hours group and the 32.0°C group vs 33.5°C group, except major bleeding occurred among 1% in the 120 hours group vs 3% in the 72 hours group (RR, 0.25 [95% CI, 0.07–0.91]). Futility analysis determined that the probability of detecting a statistically significant benefit for longer cooling, deeper cooling, or both for NICU death was less than 2%. CONCLUSIONS AND RELEVANCE Among neonates who were full-term with moderate or severe hypoxic ischemic encephalopathy, longer cooling, deeper cooling, or both compared with hypothermia at 33.5°C for 72 hours did not reduce NICU death. These results have implications for patient care and design of future trials.

Scholars from a range of disciplines use the term 'frame' to mean a variety of disjointed and incompatible concepts. This paper examines a range of framing literature, from the writings of authors including Erving Goffman, Tuen van Dijk, Serge Moscovici, George Lakoff, Alan Johnson, William Gamson, David Snow, Robert Benford and Paolo Donati. Then it develops the theoretical case for defining frames as semi-structured elements of discourse which people use to make sense of information they encounter. Additionally, this paper demonstrates the need to include social system frames, which provide patterns for understanding social relations, among the presently acknowledged frame types. Frames develop in parallel with language, vary across cultures, and shape, but are distinct from other extra-linguistic discourse forms, including myths and ideologies.

Objective To evaluate the temperature distribution among moderately preterm (MPT, 29–33 weeks) and extremely preterm (EPT, <29 weeks) infants upon neonatal intensive care unit (NICU) admission in 2012–2013, the change in admission temperature distribution for EPT infants between 2002–2003 and 2012–2013, and associations between admission temperature and mortality and morbidity for both MPT and EPT infants. Study design Prospectively collected data from 18 centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were used to examine NICU admission temperature of inborn MPT and EPT infants. Associations between admission temperature and mortality and morbidity were determined by multivariable logistic regression. EPT infants from 2002–2003 and 2012–2013 were compared. Results MPT and EPT cohorts consisted of 5818 and 3213 infants, respectively. The distribution of admission temperatures differed between the MPT vs EPT (P < .01), including the percentage <36.5°C (38.6% vs 40.9%), 36.5°C–37.5°C (57.3% vs 52.9%), and >37.5°C (4.2% vs 6.2%). For EPT infants in 2012–2013 compared with 2002–2003, the percentage of temperatures between 36.5°C and 37.5°C more than doubled and the percentage of temperatures >37.5°C more than tripled. Admission temperature was inversely associated with in-hospital mortality. Conclusions Low and high admission temperatures are more frequent among EPT than MPT infants. Compared with a decade earlier, fewer EPT infants experience low admission temperatures but more have elevated temperatures. In spite of a change in distribution of NICU admission temperature, an inverse association between temperature and mortality risk persists.

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