Global shortage of neonatal and paediatric antibiotic trials: rapid review.

OBJECTIVES: There have been few clinical trials (CTs) on antibiotics that inform neonatal and paediatric drug labelling. The rate of unlicensed and off-label prescribing in paediatrics remains high. It is unclear whether the current neonatal and paediatric antibiotic research pipeline is adequate to inform optimal drug dosing. Using the ClinicalTrials.gov registry, this review aims to establish the current global status of antibiotic CTs in children up to 18 years of age. METHODS: Studies were identified using key word searches of the ClinicalTrials.gov registry and were manually filtered using prespecified inclusion/exclusion criteria. RESULTS: 76 registered open CTs of antibiotics in children were identified globally; 23 (30%) were recruiting newborns (only 8 (11%) included preterm neonates), 52 (68%) infants and toddlers, 58 (76%) children and 54 (71%) adolescents. The majority of registered trials were late phase (10 (15%) phase 3 and 23 (35%) phase 4/pharmacovigilance). Two-thirds were sponsored by non-profit organisations, compared with pharmaceutical companies (50 (66%) vs 26 (34%), respectively). A greater proportion of non-profit funded trials were efficacy-based strategic trials (n=34, 68%), in comparison with industry-led trials, which were most often focused on safety or pharmacokinetic data (n=17, 65%). Only 2 of the 37 antibiotics listed on the May 2016 Pew Charitable Trusts antibiotic development pipeline, currently being studied in adults, appear to be currently recruiting in open paediatric CTs. CONCLUSIONS: This review highlights that very few paediatric antibiotic CTs are being conducted globally, especially in neonates. There is a striking disparity noted between antibiotic drug development programmes in adults and children

Tagging Scientific Publications using Wikipedia and Natural Language Processing Tools. Comparison on the ArXiv Dataset

In this work, we compare two simple methods of tagging scientific publications with labels reflecting their content. As a first source of labels Wikipedia is employed, second label set is constructed from the noun phrases occurring in the analyzed corpus. We examine the statistical properties and the effectiveness of both approaches on the dataset consisting of abstracts from 0.7 million of scientific documents deposited in the ArXiv preprint collection. We believe that obtained tags can be later on applied as useful document features in various machine learning tasks (document similarity, clustering, topic modelling, etc.)

On the flexibility of the design of Multiple Try Metropolis schemes

The Multiple Try Metropolis (MTM) method is a generalization of the classical Metropolis-Hastings algorithm in which the next state of the chain is chosen among a set of samples, according to normalized weights. In the literature, several extensions have been proposed. In this work, we show and remark upon the flexibility of the design of MTM-type methods, fulfilling the detailed balance condition. We discuss several possibilities and show different numerical results

Computation of Solar Radiative Fluxes by 1D and 3D Methods Using Cloudy Atmospheres Inferred from A-train Satellite Data

The main point of this study was to use realistic representations of cloudy atmospheres to assess errors in solar flux estimates associated with 1D radiative transfer models. A scene construction algorithm, developed for the EarthCARE satellite mission, was applied to CloudSat, CALIPSO, and MODIS satellite data thus producing 3D cloudy atmospheres measuring 60 km wide by 13,000 km long at 1 km grid-spacing. Broadband solar fluxes and radiances for each (1 km)2 column where then produced by a Monte Carlo photon transfer model run in both full 3D and independent column approximation mode (i.e., a 1D model)

The effects of socioeconomic status and indices of physical environment on reduced birth weight and preterm births in Eastern Massachusetts

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors.Methods: A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes ( birth weight, small for gestational age and preterm births), in a two-level hierarchical model.Results: We found effects of both individual ( education, race, prenatal care index) and area-based ( median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outcomes and a strong confounder for both area-based SEM and indices of physical environment. The effects of traffic and land use differed by level of education and median household income.Conclusion: Overall, the findings of the study suggested greater likelihood of reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health.This work is supported by the Harvard Environmental Protection Agency (EPA) Center, Grants R827353 and R-832416, and National Institute for Environmental Health Science (NIEHS) ES-0002

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Search for intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network

Gravitational-wave astronomy has been firmly established with the detection of gravitational waves from the merger of ten stellar-mass binary black holes and a neutron star binary. This paper reports on the all-sky search for gravitational waves from intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network. The search uses three independent algorithms: two based on matched filtering of the data with waveform templates of gravitational-wave signals from compact binaries, and a third, model-independent algorithm that employs no signal model for the incoming signal. No intermediate mass black hole binary event is detected in this search. Consequently, we place upper limits on the merger rate density for a family of intermediate mass black hole binaries. In particular, we choose sources with total masses M=m1+m2ϵ[120,800] M and mass ratios q=m2/m1ϵ[0.1,1.0]. For the first time, this calculation is done using numerical relativity waveforms (which include higher modes) as models of the real emitted signal. We place a most stringent upper limit of 0.20 Gpc-3 yr-1 (in comoving units at the 90% confidence level) for equal-mass binaries with individual masses m1,2=100 M and dimensionless spins χ1,2=0.8 aligned with the orbital angular momentum of the binary. This improves by a factor of ∼5 that reported after Advanced LIGO's first observing run

All-sky search for short gravitational-wave bursts in the second Advanced LIGO and Advanced Virgo run

We present the results of a search for short-duration gravitational-wave transients in the data from the second observing run of Advanced LIGO and Advanced Virgo. We search for gravitational-wave transients with a duration of milliseconds to approximately one second in the 32-4096 Hz frequency band with minimal assumptions about the signal properties, thus targeting a wide variety of sources. We also perform a matched-filter search for gravitational-wave transients from cosmic string cusps for which the waveform is well modeled. The unmodeled search detected gravitational waves from several binary black hole mergers which have been identified by previous analyses. No other significant events have been found by either the unmodeled search or the cosmic string search. We thus present the search sensitivities for a variety of signal waveforms and report upper limits on the source rate density as a function of the characteristic frequency of the signal. These upper limits are a factor of 3 lower than the first observing run, with a 50% detection probability for gravitational-wave emissions with energies of ∼10-9 Mc2 at 153 Hz. For the search dedicated to cosmic string cusps we consider several loop distribution models, and present updated constraints from the same search done in the first observing run

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells