Hypothermia for encephalopathy in low and middle-income countries (HELIX): Study protocol for a randomised controlled trial

BACKGROUND: Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18-22 months after neonatal encephalopathy, in LMICs. METHODS: We will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1-2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months. DISCUSSION: Upon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387385. Registered on 27 February 2015

Geographic origin and taxonomic status of the invasive Privet, <i>Ligustrum robustum</i> (Oleaceae) in the Mascarene Islands, determined by chloroplast DNA and RAPDs.

Information concerning the area of origin, genetic diversity and possible acquisition of germplasm through hybridisation is fundamental to understanding the evolution, ecology and possible control measures for an introduced invasive plant species. Among the most damaging of alien plants that are invading and degrading native vegetation in the Mascarene Islands of the Indian Ocean is the Tree Privet, Ligustrum robustum. Exact information about the geographic source of introduced material of this species is lacking, in part because Ligustrum is a taxonomically difficult genus. Native material of L. robustum ssp. walkeri from Sri Lanka, L. robustum ssp. robustum from northeastern India, and the closely related L. perrottetii from southern India was compared with introduced material from La Reunion and Mauritius using chloroplast DNA RFLP markers and random amplified polymorphic DNA (RAPDs). Sri Lankan and introduced material was monomorphic for the same cpDNA haplotype that was absent from south and northeast Indian Ligustrum. Sri Lankan and introduced material was also clearly distinguished from Indian Ligustrum by RAPDs. It was concluded that material introduced and established in the Mascarene Islands is derived from the Sri Lankan subspecies L. robustum ssp. walkeri. No geographic structuring of genetic variation within Sri Lanka was detected for this taxon, so the location(s) within Sri Lanka from which introduced material is derived could not be pinpointed. RAPDs indicate that L. robustum ssp. walkeri in Sri Lanka is more similar to south Indian L. perrottetii than to northeast Indian L. robustum ssp. robustum. Moreover, RAPDs showed that introduced material in La Reunion has undergone little or no loss of genetic diversity since introduction. However, there was no evidence that it is introgressed with germplasm from two other alien Ligustrum species present on La Reunion.</p