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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Optical tracking systems typically trade off between astrometric precision and field of view. In this work, we showcase a networked approach to optical tracking using very wide field-of-view imagers that have relatively low astrometric precision on the scheduled OSIRIS-REx slingshot manoeuvre around Earth on 22 Sep 2017. As part of a trajectory designed to get OSIRIS-REx to NEO 101955 Bennu, this flyby event was viewed from 13 remote sensors spread across Australia and New Zealand to promote triangulatable observations. Each observatory in this portable network was constructed to be as lightweight and portable as possible, with hardware based off the successful design of the Desert Fireball Network. Over a 4-h collection window, we gathered 15 439 images of the night sky in the predicted direction of the OSIRIS-REx spacecraft. Using a specially developed streak detection and orbit determination data pipeline, we detected 2 090 line-of-sight observations. Our fitted orbit was determined to be within about 10 km of orbital telemetry along the observed 109 262 km length of OSIRIS-REx trajectory, and thus demonstrating the impressive capability of a networked approach to Space Surveillance and Tracking.
Sulfur-bearing monazite-(Ce) occurs in silicified carbonatite at Eureka, Namibia, forming rims up to ~0.5 mm thick on earlier-formed monazite-(Ce) megacrysts. We present X-ray photoelectron spectroscopy data demonstrating that sulfur is accommodated predominantly in monazite-(Ce) as sulfate, via a clino-anhydrite-type coupled substitution mechanism. Minor sulfide and sulfite peaks in the X-ray photoelectron spectra, however, also indicate that more complex substitution mechanisms incorporating S2– and S4+ are possible. Incorporation of S6+ through clino-anhydrite-type substitution results in an excess of M2+ cations, which previous workers have suggested is accommodated by auxiliary substitution of OH– for O2–. However, Raman data show no indication of OH–, and instead we suggest charge imbalance is accommodated through F– substituting for O2–. The accommodation of S in the monazite-(Ce) results in considerable structural distortion that may account for relatively high contents of ions with radii beyond those normally found in monazite-(Ce), such as the heavy rare earth elements, Mo, Zr and V. In contrast to S-bearing monazite-(Ce) in other carbonatites, S-bearing monazite-(Ce) at Eureka formed via a dissolution–precipitation mechanism during prolonged weathering, with S derived from an aeolian source. While large S-bearing monazite-(Ce) grains are likely to be rare in the geological record, formation of secondary S-bearing monazite-(Ce) in these conditions may be a feasible mineral for dating palaeo-weathering horizons.
We present low-frequency spectral energy distributions of 60 known radio pulsars observed with the Murchison Widefield Array telescope. We searched the GaLactic and Extragalactic All-sky Murchison Widefield Array survey images for 200-MHz continuum radio emission at the position of all pulsars in the Australia Telescope National Facility (ATNF) pulsar catalogue. For the 60 confirmed detections, we have measured flux densities in 20 × 8 MHz bands between 72 and 231 MHz. We compare our results to existing measurements and show that the Murchison Widefield Array flux densities are in good agreement.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
The relative contribution of demographic, lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood.
To assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample.
Cross-sectional study of 145 991 UK Biobank participants: multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes, adjusting for confounding factors.
There were significant associations between mood disorder features and ‘any cardiovascular disease’ (depression odds ratio (OR) = 1.15, 95% CI 1.12–1.19; bipolar OR = 1.28, 95% CI 1.14–1.43) and with hypertension (depression OR = 1.15, 95% CI 1.13–1.18; bipolar OR = 1.26, 95% CI 1.12–1.42). Individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction (depression OR = 1.47, 95% CI 1.24–1.73; bipolar OR = 2.23, 95% CI 1.53–3.57) and stroke (depression OR = 2.46, 95% CI 2.10–2.80; bipolar OR = 2.31, 95% CI 1.39–3.85).
Associations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic, lifestyle and medication confounders. Psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder.
This study aims to compare conventional simultaneous integrated boost (SIB) planning technique with a hybrid SIB intensity-modulated radiation therapy (IMRT) technique with varying open tangent to IMRT field dose ratios. Furthermore, we investigated which of the dose ratios proves the most favourable as a class solution across a sample.
In total, 15 patients with conventional SIB treatment plans were re-planned with hybrid SIB IMRT technique using three differing open field:IMRT dose ratios, that is, 80:20, 70:30 and 60:40. Plans were compared using dosimetric comparison of organs at risk (OARs) and homogeneity and conformity indexes across target structures.
All hybrid plans reduced dose maximums and showed a reduction of high doses to both lungs but increased lower doses, that is, V5, with similar results discovered for the heart. Contralateral breast dose was shown to decrease V5 and V1 measures by hybrid arms, whereas increasing the V2. Left anterior descending artery dose and non-irradiated structures were reduced by all hybrid arms. The homogeneity and conformity increased across all hybrid arms. Qualitative assessment of all plans also favoured hybrid plans.
Hybrid plans produced superior dose conformity, homogeneity, reduced dose maximums and showed an improvement in most OAR parameters. The 70:30 hybrid technique exhibited greater benefits as a class solution to the sample than conventional plans due to superior dose conformity and homogeneity to target volumes.
Nepal has a high prevalence of chronic suppurative otitis media and hearing impairment. An improved understanding of patients' knowledge, attitudes, beliefs and practices is therefore important for effective healthcare planning and intervention.
Questionnaires designed to explore their current knowledge, attitudes, beliefs and practices were completed by 153 participants: 71 were affected by a known ear disease and 82 were unaffected.
In the unaffected group, 31.7 per cent considered breast milk to be a risk factor for ear infection. Home remedies (e.g. leaf paste, oils, and urine and/or bodily fluids) had been used by 42.3 per cent of the affected group. Most participants (71.9 per cent) believed that society discriminates against those with hearing impairment.
Knowledge deficits and false beliefs were found in both groups, along with a significant use of home remedies and a perception of discrimination against people with hearing impairment. These findings are relevant for healthcare providers and may aid the development of policy, interventions and public education initiatives.
In support of the Radioactive Waste Management (RWM) safety case for a geological disposal facility (GDF) in the UK, there is a regulatory requirement to consider the likelihood and consequences of nuclear criticality. Waste packages are designed to ensure that criticality is not possible during the transport and operational phases of a GDF and for a significant period post-closure. However, over longer post-closure timescales, conditions in the GDF will evolve.
For waste packages containing spent fuel, it can be shown that, under certain conditions, package flooding could result in a type of criticality event referred to as 'quasi-steady-state' (QSS). Although unlikely, this defines a 'what-if' scenario for understanding the potential consequences of post-closure criticality. This paper provides an overview of a methodology to understand QSS criticality and its application to a spent fuel waste package.
The power of such a hypothetical criticality event is typically estimated to be a few kilowatts: comparable with international studies of similar systems and the decay heat for which waste packages are designed. This work has built confidence in the methodology and supports RWM's demonstration that post-closure criticality is not a significant concern.
The ex situ lift out (EXLO) adhesion forces are reviewed and new applications of EXLO for focused ion beam (FIB)-prepared specimens are described. EXLO is used to manipulate electron transparent specimens on microelectromechanical systems carrier devices designed for in situ electron microscope analysis. A new patented grid design without a support film is described for EXLO. This new slotted grid design provides a surface for holding the specimen in place and also allows for post lift out processing. Specimens may be easily manipulated into a backside orientation to reduce FIB curtaining artifacts with this slotted grid. Large EXLO specimens can be manipulated from Xe+ plasma FIB prepared specimens. Finally, applications of EXLO and manipulation of FIB specimens using a vacuum probe lift out method are shown. The vacuum probe provides more control for placing specimens on the new slotted grids and also allows for easy manipulation into a backside configuration.