Crystallographic imperfections significantly alter material properties and their response to external stimuli, including solute-induced phase transformations. Despite recent progress in imaging ...defects using electron and X-ray techniques, in situ three-dimensional imaging of defect dynamics remains challenging. Here, we use Bragg coherent diffractive imaging to image defects during the hydriding phase transformation of palladium nanocrystals. During constant-pressure experiments we observe that the phase transformation begins after dislocation nucleation close to the phase boundary in particles larger than 300 nm. The three-dimensional phase morphology suggests that the hydrogen-rich phase is more similar to a spherical cap on the hydrogen-poor phase than to the core-shell model commonly assumed. We substantiate this using three-dimensional phase field modelling, demonstrating how phase morphology affects the critical size for dislocation nucleation. Our results reveal how particle size and phase morphology affects transformations in the PdH system.
Over 15% of probands in a large cohort of more than 1500 inherited retinal degeneration patients present with a clinical diagnosis of Stargardt disease (STGD1), a recessive form of macular dystrophy ...caused by biallelic variants in the ABCA4 gene. Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of ABCA4, sequencing of the entire ABCA4 gene or whole genome sequencing. ABCA4 c.4539 + 2028C > T, p.= ,Arg1514Leufs*36 is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour ABCA4 c.4539 + 2028C > T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that ABCA4 c.4539 + 2028C > T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.
Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine ...receptor (GlyR) α1 subunit (GLRA1). Genetic heterogeneity has been confirmed in rare sporadic cases, with mutations affecting other postsynaptic glycinergic proteins including the GlyR β subunit (GLRB), gephyrin (GPHN) and RhoGEF collybistin (ARHGEF9). However, many individuals diagnosed with sporadic hyperekplexia do not carry mutations in these genes. Here we show that missense, nonsense and frameshift mutations in SLC6A5 (ref. 8), encoding the presynaptic glycine transporter 2 (GlyT2), also cause hyperekplexia. Individuals with mutations in SLC6A5 present with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. SLC6A5 mutations result in defective subcellular GlyT2 localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na+ binding sites.
Background
Developing a shared agenda is an important step in ensuring future research has the necessary relevance.
Objective
To characterise research priority setting partnerships (PSPs) relevant to ...women’s health.
Search strategy
Included studies were identified by searching MEDLINE and the James Lind Alliance (JLA) database.
Selection criteria
Priority setting partnerships using formal consensus methods.
Data collection and analysis
Descriptive narrative to describe the study characteristics, methods, and results.
Main results
Ten national and two international PSPs were identified. All PSPs used the JLA method to identify research priorities. Nine PSPs had published a protocol. Potential research uncertainties were gathered from guidelines (two studies), Cochrane reviews (five studies), and surveys (12 studies). The number of healthcare professionals (31–287), patients (44–932), and others (33–139) who responded to the survey, and the number of uncertainties submitted (52–4767) varied. All PSPs entered confirmed research uncertainties (39–104) into interim priority setting surveys and healthcare professionals (31–287), patients (44–932), and others (33–139) responded. All PSPs entered a short list of research uncertainties into a consensus development meeting, which enabled healthcare professionals (six to 21), patients (eight to 14), and others (two to 13) to identify research priorities (ten to 15). Four PSPs have published their results.
Conclusion
Future research priority setting studies should publish a protocol, use formal consensus development methods, and ensure their methods and results are comprehensively reported.
Tweetable
Research published in @BJOGtweets highlights future research priorities across women’s health, including @FertilityTop10, @jamesmnduffy.
Tweetable
Research published in @BJOGtweets highlights future research priorities across women’s health, including @FertilityTop10, @jamesmnduffy.
This paper includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights16150
Improvement of sex education in schools is a key part of the UK government's strategy to reduce teenage pregnancy in England. We examined the effectiveness of one form of peer-led sex education in a ...school-based randomised trial of over 8000 pupils.
29 schools were randomised to either peer-led sex education (intervention) or to continue their usual teacher-led sex education (control). In intervention schools, peer educators aged 16–17 years delivered three sessions of sex education to 13–14 year-old pupils from the same schools. Primary outcome was unprotected (without condom) first heterosexual intercourse by age 16 years. Analysis was by intention to treat.
By age 16 years, significantly fewer girls reported intercourse in the peer-led arm than in the control arm, but proportions were similar for boys. The proportions of pupils reporting unprotected first sex did not differ for girls (8·4% intervention vs 8·3% control) or for boys (6·2%vs 4·7%). Stratified estimates of the difference between arms were –0·4% (95% CI –3·7% to 2·8%, p=0·79) for girls and –1·4% (–4·4% to 1·6%, p=0·36) for boys. At follow-up (mean age 16·0 years SD 0·32), girls in the intervention arm reported fewer unintended pregnancies, although the difference was borderline (2·3%vs 3·3%, p=0·07). Girls and boys were more satisfied with peer-led than teacher-led sex education, but 57% of girls and 32% of boys wanted sex education in single-sex groups.
Peer-led sex education was effective in some ways, but broader strategies are needed to improve young people's sexual health. The role of single-sex sessions should be investigated further.
Dissolution is critical to nanomaterial stability, especially for partially dealloyed nanoparticle catalysts. Unfortunately, highly active catalysts are often not stable in their reactive ...environments, preventing widespread application. Thus, focusing on the structure–stability relationship at the nanoscale is crucial and will likely play an important role in meeting grand challenges. Recent advances in imaging capability have come from electron, X-ray, and other techniques but tend to be limited to specific sample environments and/or two-dimensional images. Here, we report investigations into the defect-stability relationship of silver nanoparticles to voltage-induced electrochemical dissolution imaged in situ in three-dimensional detail by Bragg coherent diffractive imaging. We first determine the average dissolution kinetics by stationary probe rotating disk electrode in combination with inductively coupled plasma mass spectrometry, which allows in situ measurement of Ag+ ion formation. We then observe the dissolution and redeposition processes in single nanocrystals, providing unique insight about the role of surface strain, defects, and their coupling to the dissolution chemistry. The methods developed and the knowledge gained go well beyond a “simple” silver electrochemistry and are applicable to all electrocatalytic reactions where functional links between activity and stability are controlled by structure and defect dynamics.
Afar is undergoing the final stages of continental rifting and hosts the triple junction between the Red Sea, Gulf of Aden, and Main Ethiopian rifts. To better understand the nature of the crust and ...continental breakup in the region, we calculate teleseismic receiver functions across northeastern Afar and the Danakil microplate, using new data from a regional deployment in Eritrea. We estimate the Moho depth and bulk crustal VP/VS ratio using the H‐κ stacking method. The heterogeneity of our crustal thickness estimates (∼19–35 km) indicates that the Danakil microplate has undergone stretching and crustal thinning. By investigating the relationship between crustal thickness and topographic elevation, we estimate the regional crustal bulk density as ρc ≈ 2,850 ± 20 kg m−3, which is higher than expected, given the crustal thickness of the region. We show that topography is 1.5 ± 0.4 km higher than would be expected due to crustal isostasy alone. We propose that this topography is supported by the same hot mantle upwelling suggested to be responsible for the onset of rifting in East Africa. Uplift is generated due to the presence of a hot thermal anomaly beneath the plate and by thinning of the lithospheric mantle. Our results are consistent with a number of independent constraints on the thermal structure of the asthenospheric and lithospheric mantle. Evidence of melt within the crust is provided by anomalously high VP/VS ratios of >1.9, demonstrating that magma‐assisted extension continues to be important in the final stages of continental breakup.
Plain Language Summary
Afar is an area of northern Ethiopia that extends into Eritrea. It hosts three tectonic plate boundaries that are pulling apart from one another (rifting) as continental breakup is occurring. These rifting processes have led to a complicated tectonic history; isolating a small microcontinent (the Danakil) and giving rise to volcanism across the region. To better understand the nature of the crust, we study seismic data to estimate the crustal thickness and the ratio of seismic wave speeds. Our results indicate that the crust shows substantial variation in thickness, meaning that the Danakil microplate has undergone crustal thinning. We use our results to determine that dynamic mantle processes are responsible for supporting the elevation of the region. We also show that partially molten rock (magma) is likely to be present in the crust beneath northeastern Afar and the Danakil microplate, which is evidence that magma assists with continental breakup.
Key Points
Receiver functions produce the first estimates of Eritrean bulk crustal properties
The crust of Afar and the Danakil microplate is denser than global average and highly heterogeneous
Evidence found for melt within crust and for support from hotter mantle propping up topography beneath Afar and the Danakil microplate
According to recent experiments and predictions, the orientation of the polarization at the surface of a ferroelectric material can affect its surface chemistry. Here we demonstrate the converse ...effect: the chemical environment can control the polarization orientation in a ferroelectric film. In situ synchrotron x-ray scattering measurements show that high or low oxygen partial pressure induces outward or inward polarization, respectively, in an ultrathin PbTiO3 film. Ab initio calculations provide insight into surface structure changes observed during chemical switching.
A septate uterus is a uterine anomaly that may affect reproductive outcome, and is associated with an increased risk for miscarriage, subfertility and preterm birth. Resection of the septum is ...subject of debate. There is no convincing evidence concerning its effectiveness and safety. This study aims to assess whether hysteroscopic septum resection improves reproductive outcome in women with a septate uterus.
A multi-centre randomised controlled trial comparing hysteroscopic septum resection and expectant management in women with recurrent miscarriage or subfertility and diagnosed with a septate uterus. The primary outcome is live birth, defined as the birth of a living foetus beyond 24 weeks of gestational age. Secondary outcomes are ongoing pregnancy, clinical pregnancy, miscarriage and complications following hysteroscopic septum resection. The analysis will be performed according to the intention to treat principle. Kaplan-Meier curves will be constructed, estimating the cumulative probability of conception leading to live birth rate over time. Based on retrospective studies, we anticipate an improvement of the live birth rate from 35% without surgery to 70% with surgery. To demonstrate this difference, 68 women need to be randomised.
Hysteroscopic septum resection is worldwide considered as a standard procedure in women with a septate uterus. Solid evidence for this recommendation is lacking and data from randomised trials is urgently needed.
Dutch trial registry ( NTR1676 , 18th of February 2009).
Objective
To present the first national‐level report card on the state of women's preconception health in England.
Design
Cross‐sectional population‐based study.
Setting
Maternity services, England.
...Population
All pregnant women in England with a first antenatal (booking) appointment recorded in the national Maternity Services Dataset (MSDS) from April 2018 to March 2019 (n = 652 880).
Methods
We analysed the prevalence of 32 preconception indicator measures in the overall population and across socio‐demographic subgroups. Ten of these indicators were prioritised for ongoing surveillance based on modifiability, prevalence, data quality and ranking by multidisciplinary UK experts.
Results
The three most prevalent indicators were the proportion of the 22.9% of women who smoked 1 year before pregnancy who did not quit smoking before pregnancy (85.0%), those who had not taken folic acid supplementation before pregnancy (72.7%) and previous pregnancy loss (38.9%). Inequalities were observed by age, ethnicity and area‐based deprivation level. The ten indicators prioritised were not taking folic acid supplementation before pregnancy, obesity, complex social factors, living in the most deprived areas, smoking around the time of conception, overweight, pre‐existing mental health condition, pre‐existing physical health condition, previous pregnancy loss and previous obstetric complication.
Conclusions
Our findings suggest important opportunities to improve the state of preconception health and reduce socio‐demographic inequalities for women in England. In addition to MSDS data, other national data sources that record further and possibly better quality indicators could be explored and linked to build a comprehensive surveillance infrastructure.
Linked article: This article is commented on by Mairead Black, pp. 1196 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471‐0528.17483.
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