Randomized controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with intrauterine infection: study protocol

Background: Spontaneous preterm deliveries that occur before the 34th week of gestation, and particularly before the 32nd week of gestation, have been strongly associated to intrauterine infection, ascending from vagina, and represent the largest portion of neonatal deaths and neurological problems. Bacterial vaginosis, characterized by a diminished or absent flora of lactobacilli and increased colonization of several anaerobic or facultative microorganisms, increases two times the risk of preterm delivery before the 34th week. Trials of antibiotics failed to show efficacy and effectiveness against spontaneous preterm birth related to bacterial vaginosis. Some studies indicate benefit from selected probiotics to treat genitourinary infections, including bacterial vaginosis. Objective: The purpose of this study is to evaluate the effectiveness of the early administration of selected probiotics to pregnant women with asymptomatic bacterial vaginosis/intermediate degree infection to reduce the occurrence of spontaneous preterm delivery and related neonatal mortality and morbidity. Methods/Design: Women attending public prenatal care services in Rio de Janeiro will be screened to select asymptomatic pregnant women, less than 20 weeks' gestation, with no indication of elective preterm delivery. Those with vaginal pH > = 4.5 and a Nugent score between 4 and 10 (intermediate degree infection or bacterial vaginosis) will be randomized to either the placebo or the intervention group, after written informed consent. Intervention consists in the use of probiotics, Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, 2 capsules a day, each capsule containing more than one million bacilli of each strain, for 6-12 weeks, up to the 24th-25th wk of gestation. Ancillary analyses include quantification of selected cervicovaginal cytokines and genotyping of selected polymorphisms. The randomization process is stratified for history of preterm delivery and blocked. Allocation concealment was designed as well as blinding of women, caregivers and outcome evaluators. The study will be supervised by an independent monitoring committee. Outcomes under study are preterm delivery (< 34- < 32 weeks of gestation) and associated neonatal complications: early neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, and prematurity-related retinopathy; definitions were adapted from those recommended by the 2002 version of the Vermont-Oxford Network. Trial registration at NIH register: NCT00303082

Accelerating Cold Dark Matter Cosmology (ΩΛ≡0\Omega_{\Lambda}\equiv 0)

A new kind of accelerating flat model with no dark energy that is fully dominated by cold dark matter (CDM) is investigated. The number of CDM particles is not conserved and the present accelerating stage is a consequence of the negative pressure describing the irreversible process of gravitational particle creation. A related work involving accelerating CDM cosmology has been discussed before the SNe observations [Lima, Abramo & Germano, Phys. Rev. D53, 4287 (1996)]. However, in order to have a transition from a decelerating to an accelerating regime at low redshifts, the matter creation rate proposed here includes a constant term of the order of the Hubble parameter. In this case, $H_0$ does not need to be small in order to solve the age problem and the transition happens even if the matter creation is negligible during the radiation and part of the matter dominated phase. Therefore, instead of the vacuum dominance at redshifts of the order of a few, the present accelerating stage in this sort of Einstein-de Sitter CDM cosmology is a consequence of the gravitational particle creation process. As an extra bonus, in the present scenario does not exist the coincidence problem that plagues models with dominance of dark energy. The model is able to harmonize a CDM picture with the present age of the universe, the latest measurements of the Hubble parameter and the Supernovae observations.Comment: 9 pages, 6 figures, typos corrected, references added, discussion in Appendix B extende

Loss of AMP-activated protein kinase alpha 2 subunit in mouse beta-cells impairs glucose-stimulated insulin secretion and inhibits their sensitivity to hypoglycaemia

AMPK (AMP-activated protein kinase) signalling plays a key role in whole-body energy homoeostasis, although its precise role in pancreatic β-cell function remains unclear. In the present stusy, we therefore investigated whether AMPK plays a critical function in β-cell glucose sensing and is required for the maintenance of normal glucose homoeostasis. Mice lacking AMPKα2 in β-cells and a population of hypothalamic neurons (RIPCreα2KO mice) and RIPCreα2KO mice lacking AMPKα1 (α1KORIPCreα2KO) globally were assessed for whole-body glucose homoeostasis and insulin secretion. Isolated pancreatic islets from these mice were assessed for glucose-stimulated insulin secretion and gene expression changes. Cultured β-cells were examined electrophysiologically for their electrical responsiveness to hypoglycaemia. RIPCreα2KO mice exhibited glucose intolerance and impaired GSIS (glucose-stimulated insulin secretion) and this was exacerbated in α1KORIPCreα2KO mice. Reduced glucose concentrations failed to completely suppress insulin secretion in islets from RIPCreα2KO and α1KORIPCreα2KO mice, and conversely GSIS was impaired. β-Cells lacking AMPKα2 or expressing a kinase-dead AMPKα2 failed to hyperpolarize in response to low glucose, although KATP (ATP-sensitive potassium) channel function was intact. We could detect no alteration of GLUT2 (glucose transporter 2), glucose uptake or glucokinase that could explain this glucose insensitivity. UCP2 (uncoupling protein 2) expression was reduced in RIPCreα2KO islets and the UCP2 inhibitor genipin suppressed low-glucose-mediated wild-type mouse β-cell hyperpolarization, mimicking the effect of AMPKα2 loss. These results show that AMPKα2 activity is necessary to maintain normal pancreatic β-cell glucose sensing, possibly by maintaining high β-cell levels of UCP2

The age of the Galactic thin disk from Th/Eu nucleocosmochronology III. Extended sample

The first determination of the age of the Galactic thin disk from Th/Eu nucleocosmochronology was accomplished by us in Papers I and II. The present work aimed at reducing the age uncertainty by expanding the stellar sample with the inclusion of seven new objects - an increase by 37%. A set of [Th/Eu] abundance ratios was determined from spectral synthesis and merged with the results from Paper I. Abundances for the new, extended sample were analyzed with the aid of a Galactic disk chemical evolution (GDCE) model developed by us is Paper II. The result was averaged with an estimate obtained in Paper II from a conjunction of literature data and our GDCE model, providing our final, adopted disk age T_G = (8.8 +/- 1.7) Gyr with a reduction of 0.1 Gyr (6%) in the uncertainty. This value is compatible with the most up-to-date white dwarf age determinations (<~ 10 Gyr). Considering that the halo is currently presumed to be (13.5 +/- 0.7) Gyr old, our result prompts groups developing Galactic formation models to include an hiatus of (4.7 +/- 1.8) Gyr between the formation of halo and disk.Comment: 7 pages, 5 Postscript figures, accepted for publication in Astronomy & Astrophysic

Involving seldom-heard groups in a PPI process to inform the design of a proposed trial on the use of probiotics to prevent preterm birth: a case study

Background Patient and public involvement (PPI) is an important tool in approaching research challenges. However, involvement of socially and ethnically diverse populations remains limited and practitioners need effective methods of involving a broad section of the population in planning and designing research. Methods In preparation for the development of a pilot randomised controlled trial (RCT) on the use of probiotics to prevent preterm birth, we conducted a public consultation exercise in a socially disadvantaged and ethnically diverse community. The consultation aimed to meet and engage local service users in considering the acceptability of the proposed protocol, and to encourage their participation in future and ongoing patient and public involvement activities. Four discussion groups were held in the community with mothers of young children within the proposed trial region, using an inclusive approach that incorporated a modified version of the Nominal Group Technique (NGT). Bringing the consultation to the community supported the involvement of often seldom-heard participants, such as those from minority ethnic groups. Results The women involved expressed a number of concerns about the proposed protocol, including adherence to the probiotic supplement regimen and randomisation. The proposal for the RCT in itself was perceived as confirmation that probiotic supplements had potentially beneficial effects, but also that they had potentially harmful side-effects. The complexity of the women’s responses provided greater insights into the challenges of even quite simple trial designs and enabled the research team to take these concerns into account while planning the pilot trial. Conclusions The use of the NGT method allowed for a consultation of a population traditionally less likely to participate in medical research. A carefully facilitated PPI exercise can allow members to express unanticipated concerns that may not have been elicited by a survey method. Findings from such exercises can be utilised to improve clinical trial design, provide insight into the feasibility of trials, and enable engagement of often excluded population groups

Discrete symmetries, invisible axion and lepton number symmetry in an economic 3-3-1 model

We show that Peccei-Quinn and lepton number symmetries can be a natural outcome in a 3-3-1 model with right-handed neutrinos after imposing a Z_11 x Z_2 symmetry. This symmetry is suitably accommodated in this model when we augmented its spectrum by including merely one singlet scalar field. We work out the breaking of the Peccei-Quinn symmetry, yielding the axion, and study the phenomenological consequences. The main result of this work is that the solution to the strong CP problem can be implemented in a natural way, implying an invisible axion phenomenologically unconstrained, free of domain wall formation and constituting a good candidate for the cold dark matter.Comment: 17 pages, Revtex

IceCube-Gen2: A Vision for the Future of Neutrino Astronomy in Antarctica

The recent observation by the IceCube neutrino observatory of an astrophysical flux of neutrinos represents the "first light" in the nascent field of neutrino astronomy. The observed diffuse neutrino flux seems to suggest a much larger level of hadronic activity in the non-thermal universe than previously thought and suggests a rich discovery potential for a larger neutrino observatory. This document presents a vision for an substantial expansion of the current IceCube detector, IceCube-Gen2, including the aim of instrumenting a $10\,\mathrm{km}^3$ volume of clear glacial ice at the South Pole to deliver substantial increases in the astrophysical neutrino sample for all flavors. A detector of this size would have a rich physics program with the goal to resolve the sources of these astrophysical neutrinos, discover GZK neutrinos, and be a leading observatory in future multi-messenger astronomy programs.Comment: 20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Open and Hidden Charm Production in 920 GeV Proton-Nucleus Collisions

The HERA-B collaboration has studied the production of charmonium and open charm states in collisions of 920 GeV protons with wire targets of different materials. The acceptance of the HERA-B spectrometer covers negative values of xF up to xF=-0.3 and a broad range in transverse momentum from 0.0 to 4.8 GeV/c. The studies presented in this paper include J/psi differential distributions and the suppression of J/psi production in nuclear media. Furthermore, production cross sections and cross section ratios for open charm mesons are discussed.Comment: 5 pages, 9 figures, to be published in the proceedings of the 6th International Conference on Hyperons, Charm & Beauty Hadrons (BEACH04), Chicago, IL, June 27 - July 3, 200