External validation of models for predicting cumulative live birth over multiple complete cycles of IVF treatment

Acknowledgements We are grateful to the HFEA for their permission to analyse the database, extracting the requested information, and assisting with all our queries in an efficient manner. We are also thankful to the data management support of the Grampian Data Safe Haven (DaSH) and the associated financial support of NHS Research Scotland, through NHS Grampian investment in the Grampian DaSH (www.abdn.ac.uk/iahs/facilities/grampian-data-safe-haven.php). Funding This work was supported by the Elphinstone scholarship scheme at the University of Aberdeen and the Assisted Reproduction Unit at Aberdeen Fertility Centre, University of Aberdeen. The funder did not have any role in the study design; data collection, data analysis, and interpretation of data; the writing of the report; nor the decision to submit the paper for publication. S.B. has a commitment of research funding from Merck.Peer reviewedPublisher PD

350 mV, 5 GHz Class-D Enhanced Swing Differential and Quadrature VCOs in 65 nm CMOS

A new enhanced swing class-D VCO which operates from a supply voltage as low as 300 mV is presented. The architectural advantages are described along with an analysis for the oscillation frequency. Prototype differential and quadrature variants of the proposed VCO have been implemented in a 65 nm RF CMOS process with a 5 GHz VCO oscillation frequency. At a 350 mV supply, the measured phase noise performance for the quadrature VCO with a 5% tuning range is -137.1 dBc/Hz at 3 MHz offset with a power dissipation of 2.1 mW from a 0.35 V supply. The highest resulting figure-of-merit (FoM) is 198.3 dBc/Hz.©2015 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works

Factors associated with failed treatment : an analysis of 121,744 women embarking on their first IVF cycles

Peer reviewedPublisher PD

Effect of Body Mass Index on pregnancy outcomes in nulliparous women delivering singleton babies

Peer reviewedPublisher PD

Symptomatic benefits of testosterone treatment in patient subgroups : a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Acknowledgments This work was supported by the UK National Institute for Health and Care Research (NIHR)'s Health Technology Assessment Programme (project number 17/68/01). The views expressed herein are those of the authors and not necessarily those of the National Health Service, the NIHR Health Technology Assessment Programme, or the UK Department of Health and Social Care. The Health Services Research Unit at the University of Aberdeen is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, and an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. WSD is funded by an NIHR Research Professorship. CNJ is funded by an NIHR Post-Doctoral Fellowship. ShB receives NIH research grant funding. The authors are grateful to the clinical and methodological experts and patient partners who contributed to the advisory group for this study.Peer reviewedPublisher PD

In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver

Background: Maternal smoking is one of the most important modifiable risk factors for low birthweight, which is strongly associated with increased cardiometabolic disease risk in adulthood. Maternal smoking reduces the levels of the methyl donor vitamin B12 and is associated with altered DNA methylation at birth. Altered DNA methylation may be an important mechanism underlying increased disease susceptibility; however, the extent to which this can be induced in the developing fetus is unknown. Methods: In this retrospective study, we measured concentrations of cobalt, vitamin B12, and mRNA transcripts encoding key enzymes in the 1-carbon cycle in 55 fetal human livers obtained from 11 to 21 weeks of gestation elective terminations and matched for gestation and maternal smoking. DNA methylation was measured at critical regions known to be susceptible to the in utero environment. Homocysteine concentrations were analyzed in plasma from 60 fetuses. Results: In addition to identifying baseline sex differences, we found that maternal smoking was associated with sex-specific alterations of fetal liver vitamin B12, plasma homocysteine and expression of enzymes in the 1-carbon cycle in fetal liver. In the majority of the measured parameters which showed a sex difference, maternal smoking reduced the magnitude of that difference. Maternal smoking also altered DNA methylation at the imprinted gene IGF2 and the glucocorticoid receptor (GR/NR3C1). Conclusions: Our unique data strengthen studies linking in utero exposures to altered DNA methylation by showing, for the first time, that such changes are present in fetal life and in a key metabolic target tissue, human fetal liver. Furthermore, these data propose a novel mechanism by which such changes are induced, namely through alterations in methyl donor availability and changes in 1-carbon metabolism

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Background Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. Methods We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. Findings 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60–72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95–7·10]; τ²=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40–2·89]; τ²=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males’ Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). Interpretation In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-mediumterm testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity

Chromia microspheres by the sol-gel technique

Chromia microspheres were synthesized by the sol-emulsion-gel method. The solvent extraction technique was followed for the preparation of the sols. Cr2O3 crystallized as single phase in the temperature range 400 to 1300 degrees C. Complete crystallization occurred at 1300 degrees C. Spherical morphology of the powder was confirmed by scanning electron microscopy. A size range of 3-30 mu m was observed in the powder calcined at 1300 degrees C

Solvent extraction equilibria of palladium(ll) complex with 5,8-diethyl-7- hydroxydodecan-6-one oxime in some organic diluents

116-119The extraction equilibrium behaviour of palladium (II) from aqueous chloride solution with 5,8-diethyl- 7-hydroxydodecan-6-one oxime (LIX 63) in seven organic solvents has been studied. The overall extraction equilibrium is represented by the expression:Pd2 + 2 HL (0) PdL2(0)+2H- The distribution constant (KDR) of LlX 63, determined between the organic solventsand water, increases in the order: n-heptane n-hexane Kex ) is found to be independent of the solvent. Acid dissociation constant of the reagent LlX 63 is determined from 70% (vol/vol) ethanol-water medium and the overall extraction is predicted to be independent of the nature of solvent