Costs of Constraint Based Networks on a Sphere

This paper estimates the link costs of constraint based nonblocking ATM networks on a sphere. Analytical results are obtained when switches are uniformly distributed on the surface of a unit sphere and every switch has source and sink capacity of one, and the results are compared with simulations

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators

Annual prediction of shoreline erosion and subsequent recovery

publisher: Elsevier articletitle: Annual prediction of shoreline erosion and subsequent recovery journaltitle: Coastal Engineering articlelink: http://dx.doi.org/10.1016/j.coastaleng.2017.09.008 content_type: article copyright: Crown Copyright © 2017 Published by Elsevier B.V. All rights reserved

Rational Group Decision Making. A random field Ising model at T=0

A modified version of a finite random field Ising ferromagnetic model in an external magnetic field at zero temperature is presented to describe group decision making. Fields may have a non-zero average. A postulate of minimum inter-individual conflicts is assumed. Interactions then produce a group polarization along one very choice which is however randomly selected. A small external social pressure is shown to have a drastic effect on the polarization. Individual bias related to personal backgrounds, cultural values and past experiences are introduced via quenched local competing fields. They are shown to be instrumental in generating a larger spectrum of collective new choices beyond initial ones. In particular, compromise is found to result from the existence of individual competing bias. Conflict is shown to weaken group polarization. The model yields new psycho-sociological insights about consensus and compromise in groups.Comment: 25 pages, late

WHO essential medicines for children 2011-2019: age-appropriateness of enteral formulations

INTRODUCTION: The WHO Essential Medicine List for children (EMLc) is used for promoting access to medicines. The age-appropriateness of enteral (oral and rectal) formulations for children depend on their adaptability/flexibility to allow age-related or weight-related doses to be administered/prescribed and the child's ability to swallow, as appropriate. There is scant information on the age-appropriateness of essential enteral medicines for children. OBJECTIVE: To evaluate the age-appropriateness of enteral essential medicines. MATERIALS AND METHODS: Age-appropriateness of all enteral formulations indicated and recommended in the EMLc 3rd to 7th (2011-2019) editions were determined by assessing swallowability and/or dose adaptability for children under 12 years, stratified into five age groups. RESULTS: Enteral formulations in the EMLc were more age-appropriate for older children aged 6-11 years than for younger children. In the 3rd edition, for older children, 77%, n=342, of formulations were age-appropriate. For younger children, age-appropriateness decreased with age group: 34% in those aged 3-5 years, 30% in those aged 1-2 years, 22% among those aged 28 days to 11 months and 15% in those aged 0-27 days. Overall, similar proportions were found for the 7th edition. In contrast, the majority of medicines in the 7th list were age-appropriate in targeted diseases like HIV and tuberculosis. CONCLUSION: Most recommended enteral essential medicines in EMLc 2011 and 2019 were not age-appropriate for children <6 years. Medicines which are not age-appropriate must be manipulated before administration, leading to potential issues of safety and efficacy. Evaluation of the age-appropriateness of formulations for medicines to be included in EMLc could improve access to better medicines for children in the future

Settlement Of Oyster (Crassostrea-Virginica) Larvae - Effects Of Water-Flow And A Water-Soluble Chemical Cue

Although previous evidence indicates that larvae of benthic marine invertebrates can respond to waterborne cues in still water, the importance of waterborne cues in mediating natural settlement out of flowing water has been questioned. Here, we summarize the results of flume experiments demonstrating enhanced settlement of oyster larvae in small target wells (circles of 7-cm diam) with the release of a waterborne settlement cue compared to identical substrates without the cue. In concurrent still-water experiments, more oyster larvae settled in solutions of waterborne cue than in seawater controls. Velocity and electrochemical measurements of a conservative tracer verified that at low flow velocities (2 and 6 cm s(-1)) with U* value

The N-end rule pathway is a sensor of heme

The conjugation of arginine, by arginyl-transferase, to N-terminal aspartate, glutamate or oxidized cysteine is a part of the N-end rule pathway of protein degradation. We report that arginyl-transferase of either the mouse or the yeast Saccharomyces cerevisiae is inhibited by hemin (Fe3+-heme). Furthermore, we show that hemin inhibits arginyl-transferase through a redox mechanism that involves the formation of disulfide between the enzyme's Cys-71 and Cys-72 residues. Remarkably, hemin also induces the proteasome-dependent degradation of arginyl-transferase in vivo, thus acting as both a "stoichiometric" and "catalytic" down-regulator of the N-end rule pathway. In addition, hemin was found to interact with the yeast and mouse E3 ubiquitin ligases of the N-end rule pathway. One of substrate-binding sites of the yeast N-end rule's ubiquitin ligase UBR1 targets CUP9, a transcriptional repressor. This site of UBR1 is autoinhibited but can be allosterically activated by peptides that bear destabilizing N-terminal residues and interact with two other substrate-binding sites of UBR1. We show that hemin does not directly occlude the substrate-binding sites of UBR1 but blocks the activation of its CUP9-binding site by dipeptides. The N-end rule pathway, a known sensor of short peptides, nitric oxide, and oxygen, is now a sensor of heme as well. One function of the N-end rule pathway may be to coordinate the activities of small effectors, both reacting to and controlling the redox dynamics of heme, oxygen, nitric oxide, thiols, and other compounds, in part through conditional degradation of specific transcription factors and G protein regulators