Curves of Placental Weights of Live-Born Twins

The purpose of this study is to present curves of estimated placental growth in twins and to evaluate the relative contribution of gestational age, zygosity, chorionicity, fusion of the placentas, sex of the individual and of the twin pair, site of the umbilical cord insertion, birth order, maternal age, and parity. Perinatal data and placental data were obtained from 6315 live-born twin pairs from the East Flanders Prospective Twin Survey. Of 4318 twin pairs, with no missing values, the placental weights of different gestational ages were analyzed using a nonlinear multivariate Gaussian regression. Two groups were distinguished: (1) twins with two separate placentas, and (2) twins with only one placental mass (one placenta in case of monochorionic twins or two fused placentas in case of dichorionic placentas). Overall, placental weight was influenced by gestational age, fusion of the placentas, and parity. In the case of one placental mass, monozygotic dichorionic twins had the lowest weights. If two separate placentas were present, birth order played a role in favor of the first-born twin. For parity and zygosity, the differences were most pronounced between 27 and 29 weeks, whereas the difference for birth order was most pronounced between 33 and 37 weeks. In conclusion, basic physiological characteristics, routinely examined at birth, influence placental weight. Taking these covariates into account allows a better evaluation of the placental weight given a gestational age, as an indicator of growth

A general scaling relation for the critical current density in Nb3Sn

We review the scaling relations for the critical current density (Jc) in Nb3Sn wires and include recent findings on the variation of the upper critical field (Hc2) with temperature (T) and A15 composition. We highlight deficiencies in the Summers/Ekin relations, which are not able to account for the correct Jc(T) dependence. Available Jc(H) results indicate that the magnetic field dependence for all wires can be described with Kramer's flux shear model, if non-linearities in Kramer plots are attributed to A15 inhomogeneities. The strain (eps) dependence is introduced through a temperature and strain dependent Hc2*(T,eps) and Ginzburg- Landau parameter kappa1(T,eps) and a strain dependent critical temperature Tc(eps). This is more consistent than the usual Ekin unification, which uses two separate and different dependencies on Hc2*(T) and Hc2*(eps). Using a correct temperature dependence and accounting for the A15 inhomogeneities leads to a remarkable simple relation for Jc(H,T,eps). Finally, a new relation for s(eps) is proposed, based on the first, second and third strain invariants.Comment: Accepted Topical Review for Superconductor, Science and Technolog

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Indisulam targets RNA splicing and metabolism to serve as a therapeutic strategy for high-risk neuroblastoma

Neuroblastoma is the most common paediatric solid tumour and prognosis remains poor for high-risk cases despite the use of multimodal treatment. Analysis of public drug sensitivity data showed neuroblastoma lines to be sensitive to indisulam, a molecular glue that selectively targets RNA splicing factor RBM39 for proteosomal degradation via DCAF15-E3-ubiquitin ligase. In neuroblastoma models, indisulam induces rapid loss of RBM39, accumulation of splicing errors and growth inhibition in a DCAF15-dependent manner. Integrative analysis of RNAseq and proteomics data highlight a distinct disruption to cell cycle and metabolism. Metabolic profiling demonstrates metabolome perturbations and mitochondrial dysfunction resulting from indisulam. Complete tumour regression without relapse was observed in both xenograft and the Th-MYCN transgenic model of neuroblastoma after indisulam treatment, with RBM39 loss, RNA splicing and metabolic changes confirmed in vivo. Our data show that dual-targeting of metabolism and RNA splicing with anticancer indisulam is a promising therapeutic approach for high-risk neuroblastoma

Molecule-Electrode Interface Energetics in Molecular Junction: a Transition Voltage Spectroscopy Study

We assess the performances of the transition voltage spectroscopy (TVS) method to determine the energies of the molecular orbitals involved in the electronic transport though molecular junctions. A large number of various molecular junctions made with alkyl chains but with different chemical structure of the electrode-molecule interfaces are studied. In the case of molecular junctions with clean, unoxidized electrode-molecule interfaces, i.e. alkylthiols and alkenes directly grafted on Au and hydrogenated Si, respectively, we measure transition voltages in the range 0.9 - 1.4 V. We conclude that the TVS method allows estimating the onset of the tail of the LUMO density of states, at energy located 1.0 - 1.2 eV above the electrode Fermi energy. For oxidized interfaces (e.g. the same monolayer measured with Hg or eGaIn drops, or monolayers formed on a slightly oxidized silicon substrate), lower transition voltages (0.1 - 0.6 V) are systematically measured. These values are explained by the presence of oxide-related density of states at energies lower than the HOMO-LUMO of the molecules. As such, the TVS method is a useful technique to assess the quality of the molecule-electrode interfaces in molecular junctions.Comment: Accepted for publication in J. Phys. Chem C. One pdf file including manuscript, figures and supporting informatio

The DEMO magnet system – Status and future challenges

We present the pre-concept design of the European DEMO Magnet System, which has successfully passed the DEMO plant-level gate review in 2020. The main design input parameters originate from the so-called DEMO 2018 baseline, which was produced using the PROCESS systems code. It defines a major and minor radius of 9.1 m and 2.9 m, respectively, an on-axis magnetic field of 5.3 T resulting in a peak field on the toroidal field (TF) conductor of 12.0 T. Four variants, all based on low-temperature superconductors (LTS), have been designed for the 16 TF coils. Two of these concepts were selected to be further pursued during the Concept Design Phase (CDP): the first having many similarities to the ITER TF coil concept and the second being the most innovative one, based on react-and-wind (RW) Nb3Sn technology and winding the coils in layers. Two variants for the five Central Solenoid (CS) modules have been investigated: an LTS-only concept resembling to the ITER CS and a hybrid configuration, in which the innermost layers are made of high-temperature superconductors (HTS), which allows either to increase the magnetic flux or to reduce the outer radius of the CS coil. Issues related to fatigue lifetime which emerged in mechanical analyses will be addressed further in the CDP. Both variants proposed for the six poloidal field coils present a lower level of risk for future development. All magnet and conductor design studies included thermal-hydraulic and mechanical analyses, and were accompanied by experimental tests on both LTS and HTS prototype samples (i.e. DC and AC measurements, stability tests, quench evolution etc.). In addition, magnet structures and auxiliary systems, e.g. cryogenics and feeders, were designed at pre-concept level. Important lessons learnt during this first phase of the project were fed into the planning of the CDP. Key aspects to be addressed concern the demonstration and validation of critical technologies (e.g. industrial manufacturing of RW Nb3Sn and HTS long conductors, insulation of penetrations and joints), as well as the detailed design of the overall Magnet System and mechanical structures

Advance in the conceptual design of the European DEMO magnet system

The European DEMO, i.e. the demonstration fusion power plant designed in the framework of the Roadmap to Fusion Electricity by the EUROfusion Consortium, is approaching the end of the pre-conceptual design phase, to be accomplished with a Gate Review in 2020, in which all DEMO subsystems will be reviewed by panels of independent experts. The latest 2018 DEMO baseline has major and minor radius of 9.1 m and 2.9 m, plasma current 17.9 MA, toroidal field on the plasma axis 5.2 T, and the peak field in the toroidal-field (TF) conductor 12.0 T. The 900 ton heavy TF coil is prepared in four lowerature-superconductor (LTS) variants, some of them differing slightly, other significantly, from the ITER TF coil design. Two variants of the CS coils are investigated - a purely LTS one resembling the ITER CS, and a hybrid coil, in which the innermost layers made of HTS allow the designers either to increase the magnetic flux, and thus the duration of the fusion pulse, or to reduce the outer radius of the CS coil. An issue presently investigated by mechanical analyzes is the fatigue load. Two variants of the poloidal field coils are being investigated. The magnet and conductor design studies are accompanied by the experimental tests on both LTS and HTS prototype samples, covering a broad range of DC and AC tests. Testing of quench behavior of the 15 kA HTS cables, with size and layout relevant for the fusion magnets and cooled by forced flow helium, is in preparation.</p

Predicting infectious complications in neutropenic children and young people with cancer (IPD protocol)

<p>Abstract</p> <p>Background</p> <p>A common and potentially life-threatening complication of the treatment of childhood cancer is infection, which frequently presents as fever with neutropenia. The standard management of such episodes is the extensive use of intravenous antibiotics, and though it produces excellent survival rates of over 95%, it greatly inconveniences the three-fourths of patients who do not require such aggressive treatment. There have been a number of studies which have aimed to develop risk prediction models to stratify treatment. Individual participant data (IPD) meta-analysis in therapeutic studies has been developed to improve the precision and reliability of answers to questions of treatment effect and recently have been suggested to be used to answer questions regarding prognosis and diagnosis to gain greater power from the frequently small individual studies.</p> <p>Design</p> <p>In the IPD protocol, we will collect and synthesise IPD from multiple studies and examine the outcomes of episodes of febrile neutropenia as a consequence of their treatment for malignant disease. We will develop and evaluate a risk stratification model using hierarchical regression models to stratify patients by their risk of experiencing adverse outcomes during an episode. We will also explore specific practical and methodological issues regarding adaptation of established techniques of IPD meta-analysis of interventions for use in synthesising evidence derived from IPD from multiple studies for use in predictive modelling contexts.</p> <p>Discussion</p> <p>Our aim in using this model is to define a group of individuals at low risk for febrile neutropenia who might be treated with reduced intensity or duration of antibiotic therapy and so reduce the inconvenience and cost of these episodes, as well as to define a group of patients at very high risk of complications who could be subject to more intensive therapies. The project will also help develop methods of IPD predictive modelling for use in future studies of risk prediction.</p