Developing a core outcome set for future infertility research: an international consensus development study

Study question: Can a core outcome set to standardize outcome selection, collection, and reporting across future infertility research be developed? Summary answer: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCT) and systematic reviews evaluating potential treatments for infertility. What is known already: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. Study design, size, duration: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). Participants/materials, setting, methods: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. Main results and the role of chance: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Limitations, reasons for caution: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition, and an arbitrary consensus threshold. Wider implications of the findings: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Ferility and Sterility, and Human Reproduction, have committed to implementing this core outcome set. Study funding/competing interest(s): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. Hans Evers reports being the Editor Emeritus of Human Reproduction. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Annika Strandell reports consultancy fees from Guerbet. Ernest Ng reports research sponsorship from Merck. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. Trial registration number: Core Outcome Measures in Effectiveness Trials Initiative: 1023. Keywords: Consensus development study; core outcome sets; modified Delphi method; modified Nominal Group Technique; outcome measures; outcomes

A Search for Wolf-Rayet Stars in the Small Magellanic Cloud

We conducted an extensive search for Wolf-Rayet stars (W-Rs) in the SMC, using the same interference filter imaging techniques that have proved successful in finding W-Rs in more distant members of the Local Group. Photometry of some 1.6 million stellar images resulted in some 20 good candidates, which we then examined spectroscopically. Two of these indeed proved to be newly found W-Rs, bringing the total known in the SMC from 9 to 11. Other finds included previously unknown Of-type stars (one as early as O5f?p)),the recovery of the Luminous Blue Variable S18, and the discovery of a previously unknown SMC symbiotic star. More important, however, is the fact that there does not exist a significant number of W-Rs waiting to be discovered in the SMC. The number of W-Rs in the SMC is a factor of 3 lower than in the LMC (per unit luminosity), and we argue this is the result of the SMC's low metallicity on the evolution of the most massive stars.Comment: Accepted by Astrophysical Journal. Postscript version available via ftp.lowell.edu/pub/massey/smcwr.ps.gz Revised version contains slightly revised spectral types for the Of stars but is otherwise unchange

Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer.

Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases implicated in cancer invasion and metastasis. Gelatin zymography was performed on 84 human breast carcinomas and seven normal breast tissues. The precursor form of MMP-2 (72 kDa) was found in 11 (12%) samples, while its two activated forms, i.e. 62 kDa and 59 kDa, were found in three (6%) and 34 (40%) samples respectively. In contrast to MMP-2, most of the samples (52%) contained MMP-9 in its precursor form. Using ELISA, MMP-1 levels were found in 12% of the samples while MMP-3 levels were found in only 2% of the samples. Levels of MMP-2, -3 and -9 correlated inversely with numbers of nodal metastases. Neither MMP-2 nor -9 levels were significantly related to patient outcome. However, patients with high levels of a 50-kDa gelatinase band after zymography had a significantly better survival than patients with low levels. This species was never observed in normal breast tissue

The curious case of thin-body Ge crystallization

The authors investigate the templated crystallization of thin-body Ge fin structures with high aspect ratios. Experimental variables include fin thickness and thermal treatments, with fin structures oriented in the direction. Transmission electron microscopy determined that various crystal defects form during crystallization of amorphous Ge regions, most notably (111) stacking faults, twin boundaries, and small crystallites. In all cases, the nature of the defects is dependent on the fin thickness and thermal treatments applied. Using a standard 600 degrees C rapid-thermal-anneal, Ge structures with high aspect ratios crystallize with better crystal quality and fewer uncured defects than the equivalent Si case, which is a cause for optimism for thin-film Ge devices. (C) 2011 American Institute of Physics. (doi:10.1063/1.3643160

Study protocol: developing, disseminating, and implementing a core outcome set for selective fetal growth restriction in monochorionic twin pregnancies.

BACKGROUND: Selective fetal growth restriction in monochorionic twin pregnancies is associated with an increased risk of perinatal mortality and morbidity and represents a clinical dilemma. Interventions include expectant management with early preterm delivery if there are signs of fetal compromise, selective termination of the compromised twin, fetoscopic laser coagulation of the communicating placental vessels or termination of the whole pregnancy. Previous studies evaluating interventions have reported many different outcomes and outcome measures. Such variation makes comparing, contrasting, and combining results challenging, limiting ongoing research on this uncommon condition to inform clinical practice. We aim to produce, disseminate, and implement a core outcome set for selective fetal growth restriction research in monochorionic twin pregnancies. METHODS: An international steering group, including professionals, researchers, and lay experts, has been established to oversee the development of this core outcome set. The methods have been guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. Potential core outcomes will be developed by undertaking a systematic review of studies evaluating interventions for selective fetal growth restriction in monochorionic twin pregnancies. Potential core outcomes will be entered into a three-round Delphi survey and key stakeholders including clinical professionals, researchers, and lay experts will be invited to participate. Repeated reflection and rescoring of individual outcomes should encourage group and individual stakeholder convergence towards consensus outcomes which will be entered into a modified Nominal Group Technique to finalize the core outcome set. Once core outcomes have been agreed, we will establish standardized definitions and recommend high-quality measurement instruments for each outcome. DISCUSSION: The development, dissemination, and implementation of a core outcome set for selective fetal growth restriction should ensure that future research protocols select, collect, and report outcomes and outcome measures in a standardized manner. Data synthesis will be possible on a broad level and rigorous implementation should advance the quality of research studies and their effective use in order to guide clinical practice, improve patient care, maternal, short-term perinatal outcomes, and long-term neurodevelopmental outcomes. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials (COMET) registration number: 998. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42018092697 . 18th April 2018

Description of Fischer Clusters Formation in Supercooled Liquids Within Framework of Continual Theory of Defects

Liquid is represented as complicated system of disclinations according to defect description of liquids and glasses. The expressions for the linear disclination field of an arbitrary form and energy of inter-disclination interaction are derived in the framework of gauge theory of defects. It allows us to describe liquid as a disordered system of topological moments and reduce this model to the Edwards--Anderson model with large-range interaction. Within the framework of this approach vitrifying is represented as a "hierarchical" phase transition. The suggested model allows us to explain the process of the Fischer clusters formation and the slow dynamics in supercooled liquids close to the liquid--glass transition point

Nearly universal crossing point of the specific heat curves of Hubbard models

A nearly universal feature of the specific heat curves C(T,U) vs. T for different U of a general class of Hubbard models is observed. That is, the value C_+ of the specific heat curves at their high-temperature crossing point T_+ is almost independent of lattice structure and spatial dimension d, with C_+/k_B \approx 0.34. This surprising feature is explained within second order perturbation theory in U by identifying two small parameters controlling the value of C_+: the integral over the deviation of the density of states N(\epsilon) from a constant value, characterized by \delta N=\int d\epsilon |N(\epsilon)-1/2|, and the inverse dimension, 1/d.Comment: Revtex, 9 pages, 6 figure

Sodium atoms and clusters on graphite: a density functional study

Sodium atoms and clusters (N<5) on graphite (0001) are studied using density functional theory, pseudopotentials and periodic boundary conditions. A single Na atom is observed to bind at a hollow site 2.45 A above the surface with an adsorption energy of 0.51 eV. The small diffusion barrier of 0.06 eV indicates a flat potential energy surface. Increased Na coverage results in a weak adsorbate-substrate interaction, which is evident in the larger separation from the surface in the cases of Na_3, Na_4, Na_5, and the (2x2) Na overlayer. The binding is weak for Na_2, which has a full valence electron shell. The presence of substrate modifies the structures of Na_3, Na_4, and Na_5 significantly, and both Na_4 and Na_5 are distorted from planarity. The calculated formation energies suggest that clustering of atoms is energetically favorable, and that the open shell clusters (e.g. Na_3 and Na_5) can be more abundant on graphite than in the gas phase. Analysis of the lateral charge density distributions of Na and Na_3 shows a charge transfer of about 0.5 electrons in both cases.Comment: 20 pages, 6 figure