The Diderot meteorite: The second chassignite

The Diderot meteorite is a dunite discovered in Sahara. The martian origin is unambiguous and Diderot shares strong petrographical similarities with Chassigny

Petrology, geochemistry, and cosmic-ray exposure age of lherzolitic shergottite Northwest Africa 1950

Northwest Africa (NWA) 1950 is a new member of the lherzolitic shergottite clan of the Martian meteorites recently found in the Atlas Mountains. The petrological, mineralogical, and geochemical data are very close to those of the other known lherzolitic shergottites. The meteorite has a cumulate gabbroic texture and its mineralogy consists of olivine (Fo66 to Fo75), low and high-Ca pyroxenes (En78Fs19Wo2- En60Fs26W14; En53Fs16Wo31-En45Fs14Wo41), and plagioclase (An57Ab41Or1 to An40Ab57Or3; entirely converted into maskelynite during intense shock metamorphism). Accessory minerals include phosphates (merrillite), chromite and spinels, sulfides, and a glass rich in potassium. The oxygen isotopic values lie on the fractional line defined by the other SNC meteorites (Δ17O = 0.312 ‰). The composition of NWA 1950 is very similar to the other lherzolitic shergottites and suggests an origin from the same magmatic system, or at least crystallization from a close parental melt. Cosmogenic ages indicate an ejection age similar to those of the other lherzolitic shergottites. The intensity of the shock is similar to that observed in other shergottites, as shown by the occurrence of small melt pockets containing glass interwoven with stishovite

Prolonged duration of early antibiotic therapy in extremely premature infants.

BackgroundProlonged early antibiotics in extremely premature infants may have negative effects. We aimed to assess prevalence and outcomes of provision of prolonged early antibiotics to extremely premature infants in the absence of culture-confirmed infection or NEC.MethodsCohort study of infants from 13 centers born without a major birth defect from 2008-2014 who were 401-1000 grams birth weight, 22-28 weeks gestation, and survived ≥5 days without culture-confirmed infection, NEC, or spontaneous intestinal perforation. We determined the proportion of infants who received prolonged early antibiotics, defined as ≥5 days of antibiotic therapy started at ≤72 h of age, by center and over time. Associations between prolonged early antibiotics and adverse outcomes were assessed using multivariable logistic regression.ResultsA total of 5730 infants were included. The proportion of infants receiving prolonged early antibiotics varied from 30-69% among centers and declined from 49% in 2008 to 35% in 2014. Prolonged early antibiotics was not significantly associated with death (adjusted odds ratio 1.17 [95% CI: 0.99-1.40], p = 0.07) and was not associated with NEC.ConclusionsThe proportion of extremely premature infants receiving prolonged early antibiotics decreased, but significant center variation persists. Prolonged early antibiotics were not significantly associated with increased odds of death or NEC

Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains

The respiratory syncytial virus (RSV) group A variant with the 72-nucleotide duplication in the G gene, genotype ON1, was first detected in Kilifi in 2012 and has almost completely replaced previously circulating genotype GA2 strains. This replacement suggests some fitness advantage of ON1 over the GA2 viruses, and might be accompanied by important genomic substitutions in ON1 viruses. Close observation of such a new virus introduction over time provides an opportunity to better understand the transmission and evolutionary dynamics of the pathogen. We have generated and analyzed 184 RSV-A whole genome sequences (WGS) from Kilifi (Kenya) collected between 2011 and 2016, the first ON1 genomes from Africa and the largest collection globally from a single location. Phylogenetic analysis indicates that RSV-A transmission into this coastal Kenya location is characterized by multiple introductions of viral lineages from diverse origins but with varied success in local transmission. We identify signature amino acid substitutions between ON1 and GA2 viruses within genes encoding the surface proteins (G, F), polymerase (L) and matrix M2-1 proteins, some of which were identified as positively selected, and thereby provide an enhanced picture of RSV-A diversity. Furthermore, five of the eleven RSV open reading frames (ORF) (i.e. G, F, L, N and P), analyzed separately, formed distinct phylogenetic clusters for the two genotypes. This might suggest that coding regions outside of the most frequently studied G ORF play a role in the adaptation of RSV to host populations with the alternative possibility that some of the substitutions are nothing more than genetic hitchhikers. Our analysis provides insight into the epidemiological processes that define RSV spread, highlights the genetic substitutions that characterize emerging strains, and demonstrates the utility of large-scale WGS in molecular epidemiological studies

Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants

Objective This study aims to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants. Study Design In this retrospective database study, we included all ELBW infants who were 180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG > 150 mg/dL and > 200 mg/dL was performed. Results A total of 24,548 infants were included; 2,547 (10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66-1.17). Hyperglycemia and insulin use were not associated with severe ROP (OR, 1.43; 95% CI, 0.91-2.23). BG > 150 mg/dL and insulin use were associated with severe ROP (OR, 1.34; 95% CI, 1.02-1.76). Conclusions Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP.National Center for Advancing Translational Sciences of the National Institutes of Health (NIH)U.S. governmentNational Institute of Child Health and Human DevelopmentNIHNational Center for Advancing Translational Sciences of the NIHU.S. Food and Drug AdministrationCempra PharmaceuticalsDuke Univ, Dept Pediat, Sch Med, Durham, NC 27706 USADuke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USAKK Womens & Childrens Hosp, Childrens Intens Care Unit, Singapore, SingaporeUniv Fed Sao Paulo, Ecola Paulista Med, Div Neonatal Med, Sao Paulo, BrazilUniv N Carolina, Dept Pediat, Chapel Hill, NC USAMEDNAX Inc, Pediat Med Grp, Jacksonville, FL USAUniv Fed Sao Paulo, Ecola Paulista Med, Div Neonatal Med, Sao Paulo, BrazilNIH: UL1TR001117U.S. government: HHSN267200700051CNational Institute of Child Health and Human Development: K23HD068497National Institute of Child Health and Human Development: HHSN275201000003INational Institute of Child Health and Human Development: 1R01-HD081044-01National Center for Advancing Translational Sciences of the NIH: UL1TR001117U.S. Food and Drug Administration: 1R18-FD005292-01Cempra Pharmaceuticals: HHS0100201300009CWeb of Scienc

Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants

To determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely-low-birth-weight (ELBW) infants

Inhaled PGE1 in neonates with hypoxemic respiratory failure: two pilot feasibility randomized clinical trials.

BackgroundInhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized the treatment of neonatal hypoxemic respiratory failure (NHRF). However, there is lack of sustained improvement in 30 to 46% of infants. Aerosolized prostaglandins I2 (PGI2) and E1 (PGE1) have been reported to be effective selective pulmonary vasodilators. The objective of this study was to evaluate the feasibility of a randomized controlled trial (RCT) of inhaled PGE1 (IPGE1) in NHRF.MethodsTwo pilot multicenter phase II RCTs are included in this report. In the first pilot, late preterm and term neonates with NHRF, who had an oxygenation index (OI) of ≥15 and <25 on two arterial blood gases and had not previously received INO, were randomly assigned to receive two doses of IPGE1 (300 and 150 ng/kg/min) or placebo. The primary outcome was the enrollment of 50 infants in six to nine months at 10 sites. The first pilot was halted after four months for failure to enroll a single infant. The most common cause for non-enrollment was prior initiation of INO. In a re-designed second pilot, co-administration of IPGE1 and INO was permitted. Infants with suboptimal response to INO received either aerosolized saline or IPGE1 at a low (150 ng/kg/min) or high dose (300 ng/kg/min) for a maximum duration of 72 hours. The primary outcome was the recruitment of an adequate number of patients (n = 50) in a nine-month-period, with fewer than 20% protocol violations.ResultsNo infants were enrolled in the first pilot. Seven patients were enrolled in the second pilot; three in the control, two in the low-dose IPGE1, and two in the high-dose IPGE1 groups. The study was halted for recruitment futility after approximately six months as enrollment targets were not met. No serious adverse events, one minor protocol deviation and one pharmacy protocol violation were reported.ConclusionsThese two pilot RCTs failed to recruit adequate eligible newborns with NHRF. Complex management RCTs of novel therapies for persistent pulmonary hypertension of the newborn (PPHN) may require novel study designs and a longer period of time from study approval to commencement of enrollment.Trial registrationCLINICALTRIALS.GOV: Pilot one: NCT number: 00598429 registered on 10 January 2008. Last updated: 3 February 2011. Pilot two: NCT number: 01467076 17 October 2011. Last updated: 13 February 2013

Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury

In term and near-term neonates with neonatal encephalopathy, therapeutic hypothermia protocols are well established. The current focus is on how to improve outcomes further and the challenge is to find safe and complementary therapies that confer additional protection, regeneration or repair in addition to cooling. Following hypoxia-ischemia, brain injury evolves over three main phases (latent, secondary and tertiary), each with a different brain energy, perfusion, neurochemical and inflammatory milieu. While therapeutic hypothermia has targeted the latent and secondary phase, we now need therapies that cover the continuum of brain injury that spans hours, days, weeks and months after the initial event. Most agents have several therapeutic actions but can be broadly classified under a predominant action (e.g., free radical scavenging, anti-apoptotic, anti-inflammatory, neuroregeneration, and vascular effects). Promising early/secondary phase therapies include Allopurinol, Azithromycin, Exendin-4, Magnesium, Melatonin, Noble gases and Sildenafil. Tertiary phase agents include Erythropoietin, Stem cells and others. We review a selection of promising therapeutic agents on the translational pipeline and suggest a framework for neuroprotection and neurorestoration that targets the evolving injury

Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae.

Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups