Designing and implementing online assessment in the clinical workplace

Peer reviewe

Digital assessment in the clinical workplace : Design, implementation, opportunities, challenges

Peer reviewe

Anti-Müllerian hormone for the diagnosis and prediction of menopause:a systematic review

Background: The early onset of menopause is associated with increased risks of cardiovascular disease and osteoporosis. As a woman’s circulating anti-Müllerian hormone (AMH) concentration reflects the number of follicles remaining in the ovary and declines towards the menopause, serum AMH may be of value in the early diagnosis and prediction of age at menopause. Objective and Rationale: This systematic review was undertaken to determine whether there is evidence to support the use of AMH alone, or in conjunction with other markers, to diagnose menopause, to predict menopause, or to predict and/or diagnose premature ovarian insufficiency (POI). Search Methods: A systematic literature search for publications reporting on AMH in relation to menopause or POI was conducted in PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials up to 31 May 2022. Data were extracted and synthesized using the Synthesis Without Meta-analysis for diagnosis of menopause, prediction of menopause, prediction of menopause with a single/repeat measurement of AMH, validation of prediction models, short-term prediction in perimenopausal women, and diagnosis and prediction of POI. Risk-of-bias was evaluated using the Tool to Assess Risk of Bias in Cohort Studies protocol and studies at high risk of bias were excluded. Outcomes: A total of 3207 studies were identified, and 41, including 28 858 women, were deemed relevant and included. Of the three studies that assessed AMH for the diagnosis of menopause, one showed that undetectable AMH had equivalent diagnostic accuracy to elevated FSH (>22.3 mIU/ml). No study assessed whether AMH could be used to shorten the 12 months of amenorrhoea required for a formal diagnosis of menopause. Studies assessing AMH with the onset of menopause (27 publications [n = 23 835 women]) generally indicated that lower age-specific AMH concentrations are associated with an earlier age at menopause. However, AMH alone could not be used to predict age at menopause with precision (with estimates and CIs ranging from 2 to 12 years for women aged <40 years). The predictive value of AMH increased with age, as the interval of prediction (time to menopause) shortened. There was evidence that undetectable, or extremely low AMH, may aid early diagnosis of POI in young women with a family history of POI, and women presenting with primary or secondary amenorrhoea (11 studies [n = 4537]). Wider Implications: The findings of this systematic review support the use of serum AMH to study the age of menopause in population studies. The increased sensitivity of current AMH assays provides improved accuracy for the prediction of imminent menopause, but diagnostic use for individual patients has not been rigorously examined. Prediction of age at menopause remains imprecise when it is not imminent, although the finding of very low AMH values in young women is both of clinical value in indicating an increased risk of developing POI and may facilitate timely diagnosis

Association of the functional ovarian reserve with serum metabolomic profiling by nuclear magnetic resonance spectroscopy:A cross sectional study of ~400 women

Background: Women with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown. Methods: A cross-sectional study of 398 women intending to undergo IVF with pre-treatment early follicular AMH and AFC measurements. Serum lipids, lipoprotein subclasses and low-molecular-weight metabolites were quantified by NMR spectroscopy (155 metabolic measures). Associations were analysed using multivariable regression. Results: Participants were mean 35.5 (SD 4.43) years old and had a median AMH of 16 pmol/l (IQR 8.8, 28.0 pmol/l) and a median AFC of 12 (IQR 7.16). AMH showed positive associations with HDL, omega-6 and polyunsaturated fatty acids and the amino acids isoleucine, leucine and tyrosine, with effects ranging from 0.11 (95%CI 0.004 to 0.21) for total lipids in small HDL to 0.16 (0.06 to 0.26) for isoleucine, for a mean difference of one SD of metabolite per one SD increment in AMH, and negatively with acetate: − 0.31(− 0.22, − 0.004) SD per 1 SD AMH. AFC was positively associated with alanine, glutamine and glycine. Results were consistent, though less precisely estimated, when restricted to those women who were preparing for treatment because of their partner’s infertility. Conclusions: In women intending to have IVF, AMH and AFC were not associated with traditional lipid measured but were associated with a number of novel cardiovascular risk factors. Prospective studies will be required for replication, determination of causality and confirmation that ovarian reserve is impacting on metabolism rather than variation in metabolism is influencing ovarian reserve

Characterising encapsulated nuclear waste using cosmic-ray muon tomography

Tomographic imaging techniques using the Coulomb scattering of cosmic-ray muons have been shown previously to successfully identify and characterise low- and high-Z materials within an air matrix using a prototype scintillating-fibre tracker system. Those studies were performed as the first in a series to assess the feasibility of this technology and image reconstruction techniques in characterising the potential high-Z contents of legacy nuclear waste containers for the UK Nuclear Industry. The present work continues the feasibility study and presents the first images reconstructed from experimental data collected using this small-scale prototype system of low- and high-Z materials encapsulated within a concrete-filled stainless-steel container. Clear discrimination is observed between the thick steel casing, the concrete matrix and the sample materials assayed. These reconstructed objects are presented and discussed in detail alongside the implications for future industrial scenarios.Comment: 6 pages, 4 figure

ISO observations and models of galaxies with Hidden Broad Line Regions

We present ISO mid-infrared spectrophotometry and far-infrared photometry of galaxies with Hidden Broad Line Regions (HBLR). We also present radiative transfer models of their spectral energy distributions which enable us to separate the contributions from the dusty disc of the AGN and the dusty starbursts. We find that the combination of tapered discs (discs whose thickness increases with distance from the central source in the inner part but stays constant in the outer part) and starbursts provide good fits to the data. The tapered discs dominate in the mid-infrared part of the spectrum and the starbursts in the far-infrared. After correcting the AGN luminosity for anisotropic emission we find that the ratio of the AGN luminosity to the starburst luminosity, L(AGN)/L(SB), ranges from about unity for IRAS14454-4343 to about 13 for IRAS01475-0740. Our results suggest that the warm IRAS colours of HBLR are due to the relatively high L(AGN)/L(SB). Our fits are consistent with the unified model and the idea that the infrared emission of AGN is dominated by a dusty disc in the mid-infrared and starbursts in the far-infrared.Comment: A&A accepeted, 8pages 2 Figures, final versio

Association of the serum metabolomic profile by nuclear magnetic resonance spectroscopy with sperm parameters: a cross-sectional study of 325 men

Objective: To determine whether 155 circulating metabolic measures relevant to lifestyle and metabolic health are associated with sperm parameters, as measured by concentration, motility and total motile sperm count (TMSC). Study design: Cross-sectional. Setting: University Hospital. Patients: 325 men prospectively recruited between April 1, 2017 and March 31, 2019. Intervention(s): Non-fasting serum lipids, lipoprotein subclasses, and low-molecular weight metabolites (including amino acids, glycolysis and inflammatory markers) were quantified by NMR spectroscopy. Detailed demographic, lifestyle, fertility and medical history and semen analysis. Main Outcome Measure(s): Associations of serum metabolic profiles with sperm parameters. Results: Participants were mean 37.2 (SD 5.7) years, with a median sperm concentration of 35 million/ml (IQR 15, 69) and median motility of 53% (IQR 42,67). 76% of men had a TMSC >15 Million, 10% 5-15 Million and 14% <5 Million. In both univariate and confounder adjusted analyses an extensive range of lipids and lipoproteins, glycolysis related metabolites, amino acids, ketone bodies, creatinine or albumin, did not show strong statistical evidence of associated with sperm concentration, motility, or the odds of having a reduced or low TMSC (all PBonferroni > 0.0029). Higher levels of glycolysis metabolites and ketone bodies were associated with increased odds of TMSC <15M compared with ≥15M (odds ratios of ∼1.2 to 1.3), and several lipids/lipoprotein concentrations appeared to protect against very low TMSC (<5M compared with ≥5M) with odds ratios of ∼0.8 or greater. Conclusion: Several metabolites exhibit potentially clinically relevant strength of association with the odds of a low TMSC and warrant replication

The valence-fluctuating ground state of plutonium

A central issue in material science is to obtain understanding of the electronic correlations that control complex materials. Such electronic correlations frequently arise because of the competition of localized and itinerant electronic degrees of freedom. Although the respective limits of well-localized or entirely itinerant ground states are well understood, the intermediate regime that controls the functional properties of complex materials continues to challenge theoretical understanding. We have used neutron spectroscopy to investigate plutonium, which is a prototypical material at the brink between bonding and nonbonding configurations. Our study reveals that the ground state of plutonium is governed by valence fluctuations, that is, a quantum mechanical superposition of localized and itinerant electronic configurations as recently predicted by dynamical mean field theory. Our results not only resolve the long-standing controversy between experiment and theory on plutonium’s magnetism but also suggest an improved understanding of the effects of such electronic dichotomy in complex materials.JRC.E.6-Actinide researc