Recommendations for the design of therapeutic trials for neonatal seizures

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from welldesigned clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population

A Comparison of Resting State Brain Activity in Humans and Chimpanzees

In humans, the wakeful resting condition is characterized by a default mode of brain function involving high levels of activity within a functionally connected network of brain regions. This network has recently been implicated in mental self-projection into the past, the future, or another individual's perspective. Here we use [(18)F]-fluorodeoxyglucose positron emission tomography imaging to assess resting-state brain activity in our closest living relative, the chimpanzee, as a potential window onto their mental world and compare these results with those of a human sample. We find that, like humans, chimpanzees show high levels of activity within default mode areas, including medial prefrontal and medial parietal cortex. Chimpanzees differ from our human sample in showing higher levels of activity in ventromedial prefrontal cortex and lower levels of activity in left-sided cortical areas involved in language and conceptual processing in humans. Our results raise the possibility that the resting state of chimpanzees involves emotionally laden episodic memory retrieval and some level of mental self-projection, albeit in the absence of language and conceptual processing

An Artificial Placenta Protects against Lung Injury and Promotes Continued Lung Development in Extremely Premature Lambs

An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could protect premature lungs from injury and promote continued development. Preterm lambs at estimated gestational age (EGA) 114-128 days (term = 145) were delivered by Caesarian section and managed in one of three groups: AP, mechanical ventilation (MV), or tissue control (TC). Artificial placenta lambs (114 days EGA, n = 3; 121 days, n = 5) underwent venovenous (VV)-ECLS with jugular drainage and umbilical vein reinfusion for 7 days, with a fluid-filled, occluded airway. Mechanical ventilation lambs (121 days, n = 5; 128 days, n = 5) underwent conventional MV until failure or maximum 48 hours. Tissue control lambs (114 days, n = 3; 121 days, n = 5; 128 days, n = 5) were sacrificed at delivery. At the conclusion of each experiment, lungs were procured and sectioned. Hematoxylin and eosin (H&E) slides were scored 0-4 in seven injury categories, which were summed for a total injury score. Slides were also immunostained for platelet-derived growth factor receptor (PDGFR)-α and α-actin; lung development was quantified by the area fraction of double-positive tips of secondary alveolar septa. Support duration of AP lambs was 163 ± 9 (mean ± SD) hours, 4 ± 3 for early MV lambs, and 40 ± 6 for late MV lambs. Total injury scores at 121 days were 1.7 ± 2.1 for AP vs. 5.5 ± 1.6 for MV (p = 0.02). Using immunofluorescence, double-positive tip area fraction at 121 days was 0.017 ± 0.011 in AP lungs compared with 0.003 ± 0.003 in MV lungs (p < 0.001) and 0.009 ± 0.005 in TC lungs. At 128 days, double-positive tip area fraction was 0.012 ± 0.007 in AP lungs compared with 0.004 ± 0.004 in MV lungs (p < 0.001) and 0.016 ± 0.009 in TC lungs. The AP is protective against lung injury and promotes lung development compared with mechanical ventilation in premature lambs.http://deepblue.lib.umich.edu/bitstream/2027.42/192081/2/an_artificial_placenta_protects_against_lung.12.pdfPublished versio