Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention

Unconfined Specimens

ABSTRACT: Effective diffusion coefficients, D*, of chloride and zinc diffusing in saturated, unconfined specimens of a compacted sandclay mixture are measured for three specimen lengths, L (2.91, 5.83, and 11.60 cm) and three test durations (7, 14, and 21 days). For a specimen length of 2.91 cm, both the chloride and zinc D* values tend to decrease with increasing test duration, possibly due to the measurement of concentration-dependent D* values. For a 14-day test duration, no consistent trend in D* with specimen length is observed, but the overall effect of specimen length on D* is minor relative to the range of measured D* values. A 21-day test duration provides the best correlation between the D* values based on reservoir concentrations, DiScs, and the D* values based on soil concentrations, D~oil, for chloride for a given test regardless of the specimen length. The effect of test duration on the correlation between D~cs and D~oit for zinc is minor based on the relatively narrow range of measured zinc D* values. The observed effects of specimen length on the correlation between D~¢s and D~oil for a given test are consistent with the more uniform final porosity distributions in the shorter specimens and the contrasting effects of the non-linear distributions in porosity and dry density that become less significant as the specimen length increases. KEYWORDS: adsorption, attapulgite clay, batch equilibrium, chloride diffusion, contaminant transport, diffusion testing, Freundlich isotherm, sand-clay mixture, swelling, zinc diffusion Over the past -30 years, diffusion testing has been performed in several different disciplines (e.g., soil science, geology, oceanography, geotechnical engineering) for several different purposes, including diffusion of nutrients to plant roots (Olsen and Kemper 1968), characterization of pore water in geologic deposits Several different types of diffusion testing procedures can be used, test durations have ranged from a few hours to several months, and the specimen volumes have ranged from as small as 10 cm 3 to more than 944 cm 3 (Shacketford 1991). Practical limitations to some, if not all, of the different test methods undoubtedly exist, and variability in test duration and specimen size may have an effect on determination of the measured diffusion coefficients. As a result, an evaluation of the factors potentially affecting the measurement of effective diffusion coefficients is needed. Such an evaluation is particularly of interest to geotechnical engineers associated with the design and evaluation of waste containment barriers because of the increasing importance placed on contaminant transport, in general, and diffusive transport, in particular, in such applications. The primary objective of this study is to evaluate the potential influence of test duration and specimen length on the diffusion of chloride and zinc in compacted, unconfined specimens of a sandclay mixture. The evaluation is based on the single reservoir, decreasing source concentration method that has been used extensively in the measurement of effective diffusion coefficients associated with waste disposal applications Materials and Methods Soil The soil used in this study is a mixture of 75% sand and 25% attapulgite clay (dry weight basis). Physical and chemical properties of the sand and attapulgite clay are provided i

Implementation and evaluation of a transit dosimetry system for treatment verification

PURPOSE: To evaluate a formalism for transit dosimetry using a phantom study and prospectively evaluate the protocol on a patient population undergoing 3D conformal radiotherapy. METHODS: Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. The measured EPID dose map was back-projected using the planning CT images to calculate dose at pre-specified points within the patient using commercially available software, EPIgray (DOSIsoft, France). This software compared computed back-projected dose with treatment planning system dose. A series of tests were performed on solid water phantoms (linearity, field size effects, off-axis effects). 37 patients were enrolled in the prospective study. RESULTS: The EPID dose response was stable and linear with dose. For all tested field sizes the agreement was good between EPID-derived and treatment planning system dose in the central axis, with performance stability up to a measured depth of 18cm (agreement within -0.5% at 10cm depth on the central axis and within -1.4% at 2cm off-axis). 126 transit images were analysed of 37 3D-conformal patients. Patient results demonstrated the potential of EPIgray with 91% of all delivered fields achieved the initial set tolerance level of ΔD of 0±5-cGy or %ΔD of 0±5%. CONCLUSIONS: The in vivo dose verification method was simple to implement, with very few commissioning measurements needed. The system required no extra dose to the patient, and importantly was able to detect patient position errors that impacted on dose delivery in two of cases

Propagation en contexte arrière-arc : premiers résultats de la campagne ProFeTi (Bassin Nord-Fidjien, Pacifique SW)

Au centre du bassin Nord-Fidjien, le segment d'accrétion NS, qui se propage vers le Nord aux dépens du segment N15 depuis au moins 1 Ma, a été échantillonné pendant la campagne ProFeTi du NO Alis. Malgré sa position arrière-arc, aucune contamination géochimique caractéristique d'une subduction n'est perceptible. L'échantillonnage étudié montre que les réservoirs magmatiques de ce segment en propagation évoluent dans une perpétuelle dynamique de recherche d'équilibre thermique et chimique, perturbée par les actions conjuguées suivantes : l'éloignement de la pointe du propagateur par rapport aux zones de réalimentations focalisées sous le centre du segment, des réalimentations successives par des liquides primitifs évoluant avec l'état de maturité du propagateur, et un effet de paroi froide provenant du segment N15, dans lequel la lithosphère de la pointe du segment NS se propage. (Résumé d'auteur

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Gene transfer into hepatocytes using asialoglycoprotein receptor mediated endocytosis of DNA complexed with an artificial tetra-antennary galactose ligand

We have constructed an artificial ligand for the hepatocyte-specific asialoglycoprotein receptor for the purpose of generating a synthetic delivery system for DNA. This ligand has a tetra-antennary structure, containing four terminal galactose residues on a branched carrier peptide. The carbohydrate residues of this glycopeptide were introduced by reductive coupling of lactose to the alpha- and epsilon-amino groups of the two N-terminal lysines on the carrier peptide. The C-terminus of the peptide, containing a cysteine separated from the branched N-terminus by a 10 amino acid spacer sequence, was used for conjugation to 3-(2-pyridyldithio)propionate-modified polylysine via disulfide bond formation. Complexes containing plasmid DNA bound to these galactose-polylysine conjugates have been used for asialoglycoprotein receptor-mediated transfer of a luciferase gene into human (HepG2) and murine (BNL CL.2) hepatocyte cell lines. Gene transfer was strongly promoted when amphipathic peptides with pH-controlled membrane-disruption activity, derived from the N-terminal sequence of influenza virus hemagglutinin HA-2, were also present in these DNA complexes. Thus, we have essentially borrowed the small functional domains of two large proteins, asialoglycoprotein and hemagglutinin, and assembled them into a supramolecular complex to generate an efficient gene-transfer system

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

Les adakites et les andésites riches en Mg du volcan Pichincha (Equateur) : témoins de la fusion de la croûte océanique et de la métasomatose adakitique sous la zone volcanique nord des Andes

Situatedin the fore-arc of the Northern Volcanic Zone (NVZ) of the Andes in Ecuador, Pichincha volcano is an active edifice where have been erupted unusual magmas as adakites and high-Mg andesites. The particular geodynamic setting of the ecuadorian margin (i.e. the flat subduction of the Carnegie Ridge) suggests that thermo-barometric conditions for the partial melting of the oceanic crust are accomplished beneath this volcano. Pichincha adakites possess all the geochemical and isotopic characteristics of slab melts described in various other arc settings. High-Mg andesites with geochemical characteristics close to those of adakites present strong enrichments in MgO that suggest that, once they were produced by ca. 10 % partial melting of the downgoing subducted slab, some adakites en route to the surface strongly interacted with the peridotitic mantle wedge. Adakitic magmas could then represent, as in many other arcs where slab melting occurs, the principal metasomatic agent of the mantle in the NVZ in Ecuador

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