Use of biochemical tests of placental function for improving pregnancy outcome

BACKGROUND: The placenta has an essential role in determining the outcome of pregnancy. Consequently, biochemical measurement of placentally-derived factors has been suggested as a means to improve fetal and maternal outcome of pregnancy. OBJECTIVES: To assess whether clinicians' knowledge of the results of biochemical tests of placental function is associated with improvement in fetal or maternal outcome of pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised, cluster-randomised or quasi-randomised controlled trials assessing the merits of the use of biochemical tests of placental function to improve pregnancy outcome.Studies were eligible if they compared women who had placental function tests and the results were available to their clinicians with women who either did not have the tests, or the tests were done but the results were not available to the clinicians. The placental function tests were any biochemical test of placental function carried out using the woman's maternal biofluid, either alone or in combination with other placental function test/s. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and assessed trial quality. Authors of published trials were contacted for further information. MAIN RESULTS: Three trials were included, two quasi-randomised controlled trials and one randomised controlled trial. One trial was deemed to be at low risk of bias while the other two were at high risk of bias. Different biochemical analytes were measured - oestrogen was measured in one trial and the other two measured human placental lactogen (hPL). One trial did not contribute outcome data, therefore, the results of this review are based on two trials with 740 participants.There was no evidence of a difference in the incidence of death of a baby (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.36 to 2.13, two trials, 740 participants (very low quality evidence)) or the frequency of a small-for-gestational-age infant (RR 0.44, 95% CI 0.16 to 1.19, one trial, 118 participants (low quality evidence)).In terms of this review's secondary outcomes, there was no evidence of a clear difference between women who had biochemical tests of placental function compared with standard antenatal care for the incidence of stillbirth (RR 0.56, 95% CI 0.16 to 1.88, two trials, 740 participants (very low quality evidence)) or neonatal death (RR 1.62, 95% CI 0.39 to 6.74, two trials, 740 participants, very low quality evidence)) although the directions of any potential effect were in opposing directions. There was no evidence of a difference between groups in elective delivery (RR 0.98, 95% CI 0.84 to 1.14, two trials, 740 participants (low quality evidence)), caesarean section (one trial, RR 0.48, 95% CI 0.15 to 1.52, one trial, 118 participants (low quality evidence)), change in anxiety score (mean difference -2.40, 95% CI -4.78 to -0.02, one trial, 118 participants), admissions to neonatal intensive care (RR 0.32, 95% CI 0.03 to 3.01, one trial, 118 participants), and preterm birth before 37 weeks' gestation (RR 2.90, 95% CI 0.12 to 69.81, one trial, 118 participants). One trial (118 participants) reported that there were no cases of serious neonatal morbidity. Maternal death was not reported.A number of this review's secondary outcomes relating to the baby were not reported in the included studies, namely: umbilical artery pH seven days, pre-eclampsia, eclampsia, and women's perception of care). AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of biochemical tests of placental function to reduce perinatal mortality or increase identification of small-for-gestational-age infants. However, we were only able to include data from two studies that measured oestrogens and hPL. The quality of the evidence was low or very low.Two of the trials were performed in the 1970s on women with a variety of antenatal complications and this evidence cannot be generalised to women at low-risk of complications or groups of women with specific pregnancy complications (e.g. fetal growth restriction). Furthermore, outcomes described in the 1970s may not reflect what would be expected at present. For example, neonatal mortality rates have fallen substantially, such that an infant delivered at 28 weeks would have a greater chance of survival were those studies repeated; this may affect the primary outcome of the meta-analysis.With data from just two studies (740 women), this review is underpowered to detect a difference in the incidence of death of a baby or the frequency of a small-for-gestational-age infant as these have a background incidence of approximately 0.75% and 10% of pregnancies respectively. Similarly, this review is underpowered to detect differences between serious and/or rare adverse events such as severe neonatal morbidity. Two of the three included studies were quasi-randomised, with significant risk of bias from group allocation. Additionally, there may be performance bias as in one of the two studies contributing data, participants receiving standard care did not have venepuncture, so clinicians treating participants could identify which arm of the study they were in. Future studies should consider more robust randomisation methods and concealment of group allocation and should be adequately powered to detect differences in rare adverse events.The studies identified in this review examined two different analytes: oestrogens and hPL. There are many other placental products that could be employed as surrogates of placental function, including: placental growth factor (PlGF), human chorionic gonadotrophin (hCG), plasma protein A (PAPP-A), placental protein 13 (PP-13), pregnancy-specific glycoproteins and progesterone metabolites and further studies should be encouraged to investigate these other placental products. Future randomised controlled trials should test analytes identified as having the best predictive reliability for placental dysfunction leading to small-for-gestational-age infants and perinatal mortality

Small-amplitude normal modes of a vortex in a trapped Bose-Einstein condensate

We consider a cylindrically symmetric trap containing a small Bose-Einstein condensate with a singly quantized vortex on the axis of symmetry. A time-dependent variational Lagrangian analysis yields the small-amplitude dynamics of the vortex and the condensate, directly determining the equations of motion of the coupled normal modes. As found previously from the Bogoliubov equations, there are two rigid dipole modes and one anomalous mode with a negative frequency when seen in the laboratory frame.Comment: 4 pages, no figures, Revte

Development of core outcome sets for studies relating to awareness and clinical management of reduced fetal movement

Objective: This study aimed to create core outcome sets (COSs) for use in research studies relating to the awareness and clinical management of reduced fetal movement (RFM). Design: Delphi survey and consensus process. Setting: International. Population: A total of 128 participants (40 parents, 19 researchers and 65 clinicians) from 16 countries. Methods: A systematic literature review was conducted to identify outcomes in studies of interventions relating to the awareness and the clinical management of RFM. Using these outcomes as a preliminary list, stakeholders rated the importance of these outcomes for inclusion in COSs for studies of: (i) awareness of RFM; and (ii) clinical management of RFM. Main outcome measures: Preliminary lists of outcomes were discussed at consensus meetings where two COSs (one for studies of RFM awareness and one for studies of clinical management of RFM). Results: The first round of the Delphi survey was completed by 128 participants, 66% of whom (n = 84) completed all three rounds. Fifty outcomes identified by the systematic review, after multiple definitions were combined, were voted on in round one. Two outcomes were added in round one, and as such 52 outcomes were voted on in two lists in rounds two and three. The COSs for studies of RFM awareness and clinical management are comprised of eight outcomes (four maternal and four neonatal) and 10 outcomes (two maternal and eight neonatal), respectively. Conclusions: These COSs provide researchers with the minimum set of outcomes to be measured and reported in studies relating to the awareness and the clinical management of RFM.</p

Entanglement of a Single Spin-1 Object: An Example of Ubiquitous Entanglement

Using a single spin-1 object as an example, we discuss a recent approach to quantum entanglement. The key idea of the approach consists in presetting of basic observables in the very definition of quantum system. Specification of basic observables defines the dynamic symmetry of the system. Entangled states of the system are then interpreted as states with maximal amount of uncertainty of all basic observables. The approach gives purely physical picture of entanglement. In particular, it separates principle physical properties of entanglement from inessential. Within the model example under consideration, we show relativity of entanglement with respect to dynamic symmetry and argue existence of single-particle entanglement. A number of physical examples are considered.Comment: 12 pages, 2 figure : title has been changed, paper is re-organized, new section "Violation of Bell-type condition by single spin-1" is adde

RHESSI Results -- Time For a Rethink?

Hard X-rays and gamma-rays are the most direct signatures of energetic electrons and ions in the sun's atmosphere which is optically thin at these energies and their radiation involves no coherent processes. Being collisional they are complementary to gyro-radiation in probing atmospheric density as opposed to magnetic field and the electrons are primarily 10--100 keV in energy, complementing the (>100 keV) electrons likely responsible for microwave bursts. The pioneering results of the Ramaty High Energy Solar Spectroscopic Imager (RHESSI) are raising the first new major questions concerning solar energetic particles in many years. Some highlights of these results are discussed -- primarily around RHESSI topics on which the authors have had direct research involvement -- particularly when they are raising the need for re-thinking of entrenched ideas. Results and issues are broadly divided into discoveries in the spatial, temporal and spectral domains, with the main emphasis on flare hard X-rays/fast electrons but touching also on gamma-rays/ions, non-flare emissions, and the relationship to radio bursts.Comment: Proceedings CESRA Workshop 2004: "The High Energy Solar Corona: Waves, Eruptions, Particles", Lecture Notes in Physics, 2006 (accepted

A compensatory mutagenesis study of a conserved hairpin in the M gene segment of influenza A virus shows its role in virus replication

RNA structures are increasingly recognized to be of importance during influenza A virus replication. Here, we investigated a predicted conserved hairpin in the M gene segment (nt 967-994) within the region of the vRNA 5′ packaging signal. The existence of this RNA structure and its possible role in virus replication was investigated using a compensatory mutagenesis approach. Mutations were introduced in the hairpin stem, based on natural variation. Virus replication properties were studied for the mutant viruses with disrupted and restored RNA structures. Viruses with structure-disrupting mutations had lower virus titers and a significantly reduced median plaque size when compared with the wild-type (WT) virus, while viruses with structure restoring-mutations replicated comparable to WT. Moreover, virus replication was also reduced when mutations were introduced in the hairpin loop, suggesting its involvement in RNA interactions. Northern blot and FACS experiments were performed to study differences in RNA levels as well as production of M1 and M2 proteins, expressed via alternative splicing. Stem-disruptive mutants caused lower vRNA and M2 mRNA levels and reduced M2 protein production at early time-points. When the RNA structure was restored, vRNA, M2 mRNA and M2 protein levels were increased, demonstrating a compensatory effect. Thus, this study provides evidence for functional importance of the predicted M RNA structure and suggests its role in splicing regulation

Gupta–Bleuler Quantization of the Maxwell Field in Globally Hyperbolic Space-Times

We give a complete framework for the Gupta–Bleuler quantization of the free electromagnetic field on globally hyperbolic space-times. We describe one-particle structures that give rise to states satisfying the microlocal spectrum condition. The field algebras in the so-called Gupta–Bleuler representations satisfy the time-slice axiom, and the corresponding vacuum states satisfy the microlocal spectrum condition. We also give an explicit construction of ground states on ultrastatic space-times. Unlike previous constructions, our method does not require a spectral gap or the absence of zero modes. The only requirement, the absence of zero-resonance states, is shown to be stable under compact perturbations of topology and metric. Usual deformation arguments based on the time-slice axiom then lead to a construction of Gupta–Bleuler representations on a large class of globally hyperbolic space-times. As usual, the field algebra is represented on an indefinite inner product space, in which the physical states form a positive semi-definite subspace. Gauge transformations are incorporated in such a way that the field can be coupled perturbatively to a Dirac field. Our approach does not require any topological restrictions on the underlying space-time

Vortices and dynamics in trapped Bose-Einstein condensates

I review the basic physics of ultracold dilute trapped atomic gases, with emphasis on Bose-Einstein condensation and quantized vortices. The hydrodynamic form of the Gross-Pitaevskii equation (a nonlinear Schr{\"o}dinger equation) illuminates the role of the density and the quantum-mechanical phase. One unique feature of these experimental systems is the opportunity to study the dynamics of vortices in real time, in contrast to typical experiments on superfluid $^4$He. I discuss three specific examples (precession of single vortices, motion of vortex dipoles, and Tkachenko oscillations of a vortex array). Other unusual features include the study of quantum turbulence and the behavior for rapid rotation, when the vortices form dense regular arrays. Ultimately, the system is predicted to make a quantum phase transition to various highly correlated many-body states (analogous to bosonic quantum Hall states) that are not superfluid and do not have condensate wave functions. At present, this transition remains elusive. Conceivably, laser-induced synthetic vector potentials can serve to reach this intriguing phase transition.Comment: Accepted for publication in Journal of Low Temperature Physics, conference proceedings: Symposia on Superfluids under Rotation (Lammi, Finland, April 2010