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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
We demonstrate the importance of radio selection in probing heavily obscured galaxy populations. We combine Evolutionary Map of the Universe (EMU) Early Science data in the Galaxy and Mass Assembly (GAMA) G23 field with the GAMA data, providing optical photometry and spectral line measurements, together with Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry, providing IR luminosities and colours. We investigate the degree of obscuration in star-forming galaxies, based on the Balmer decrement (BD), and explore how this trend varies, over a redshift range of $0<z<0.345$. We demonstrate that the radio-detected population has on average higher levels of obscuration than the parent optical sample, arising through missing the lowest BD and lowest mass galaxies, which are also the lower star formation rate (SFR) and metallicity systems. We discuss possible explanations for this result, including speculation around whether it might arise from steeper stellar initial mass functions in low mass, low SFR galaxies.
The building of online atomic and molecular databases for astrophysics and for other research fields started with the beginning of the internet. These databases have encompassed different forms: databases of individual research groups exposing their own data, databases providing collected data from the refereed literature, databases providing evaluated compilations, databases providing repositories for individuals to deposit their data, and so on. They were, and are, the replacement for literature compilations with the goal of providing more complete and in particular easily accessible data services to the users communities. Such initiatives involve not only scientific work on the data, but also the characterization of data, which comes with the “standardization” of metadata and of the relations between metadata, as recently developed in different communities. This contribution aims at providing a representative overview of the atomic and molecular databases ecosystem, which is available to the astrophysical community and addresses different issues linked to the use and management of data and databases. The information provided in this paper is related to the keynote lecture “Atomic and Molecular Databases: Open Science for better science and a sustainable world” whose slides can be found at DOI : doi.org/10.5281/zenodo.6979352 on the Zenodo repository connected to the “cb5-labastro” Zenodo Community (https://zenodo.org/communities/cb5-labastro).
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Sleep disturbances are important symptoms to monitor in people with bipolar disorder (BD) but the precise longitudinal relationships between sleep and mood remain unclear. We aimed to examine associations between stable and dynamic aspects of sleep and mood in people with BD, and assess individual differences in the strength of these associations.
Methods
Participants (N = 649) with BD-I (N = 400) and BD-II (N = 249) provided weekly self-reports of insomnia, depression and (hypo)mania symptoms using the True Colours online monitoring tool for 21 months. Dynamic structural equation models were used to examine the interplay between weekly reports of insomnia and mood. The effects of clinical and demographic characteristics on associations were also assessed.
Results
Increased variability in insomnia symptoms was associated with increased mood variability. In the sample as a whole, we found strong evidence of bidirectional relationships between insomnia and depressive symptoms but only weak support for bidirectional relationships between insomnia and (hypo)manic symptoms. We found substantial variability between participants in the strength of prospective associations between insomnia and mood, which depended on age, gender, bipolar subtype, and a history of rapid cycling.
Conclusions
Our results highlight the importance of monitoring sleep in people with BD. However, researchers and clinicians investigating the association between sleep and mood should consider subgroup differences in this relationship. Advances in digital technology mean that intensive longitudinal data on sleep and mood are becoming increasingly available. Novel methods to analyse these data present an exciting opportunity for furthering our understanding of BD.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
$270 \,\mathrm{deg}^2$
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
$\mu\mathrm{Jy\ beam}^{-1}$
rms at a spatial resolution of
$\sim$
11–18 arcsec, resulting in a catalogue of
$\sim$
220 000 sources, of which
$\sim$
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
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.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
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.
Results
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.
Conclusions
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.
No crucial experiment demonstrates that four hue categories
are needed to describe color appearance. Instead, converging lines
of evidence suggest that the terms red, yellow, green, and blue
are sufficient and precise enough for deriving color discrimination
functions and for a useful model constraining relations between color
appearance and neuronal responses. Such a model need not be based
on linguistic universals. Until something better is available, this
“standard model” holds.
With the growing human population, and their improving wealth, it is predicted that there will be significant increases in demand for livestock products (mainly meat and milk). Recent years have demonstrated that the growth in livestock production has generally had significant impacts on wildlife worldwide; and these are, usually, negative. Here I review the interactions between livestock and wildlife and assess the mechanisms through which these interactions occur. The review is framed within the context of the socio-ecological system whereby people are as much a part of the interaction between livestock and wildlife as the animal species themselves. I highlight areas of interaction that are mediated through effects on the forage supply (vegetation) – neutral, positive and negative – however, the review broadly analyses the impacts of livestock production activities. The evidence suggests that it is not the interaction between the species themselves but the ancillary activities associated with livestock production (e.g. land use change, removal of predators, provision of water points) that are the major factors affecting the outcome for wildlife. So in future, there are two key issues that need to be addressed – first, we need to intensify livestock production in areas of ‘intensive’ livestock production in order to reduce the pressure for land use change to meet the demand for meat (land sparing). And second, if wildlife is to survive in areas where livestock production dominates, it will have to be the people part of the socio-ecological system that sees the benefits of having wildlife co-exist with livestock on farming lands (land sharing and win-win).
Sugarcane is an important forage resource in sub-tropical and tropical areas as it is used during the winter or dry season when the growth rate of pastures is significantly reduced. The current research study assessed the effect of four vertical sections of sugarcane in a pen trial and the level of sugarcane utilization in a grazing trial on the ingestive behaviour and forage intake of two age groups of steers (1 and 2 years old). The pen trial was comprised of two simultaneous 4 × 4 balanced Latin square designs (one for each age group of animals) of four periods, four animals and four feeding treatments, which consisted of four equal vertical sections of sugarcane. Dry matter (DM) and digestible DM (DDM) intake per kilogram of metabolic weight declined gradually from top to bottom of the sugarcane, with no significant differences between the age groups of steers. This difference in intake was associated with a decline in intake of neutral detergent fibre (NDF) as a proportion of the liveweight of the animal and an increase of total chewing time per kilogram of DM or NDF from top to bottom of the sugarcane. It was concluded that the toughness of plant material played a significant role regulating intake, which was higher for the top sections of sugarcane. In the grazing trial, steers of both age groups grazed down sugarcane in three plots over 9 days. Steers grazed up to four distinctive grazing strata. Digestible DM intake (DDM intake) was high at low levels of horizontal utilization of the top grazing stratum but DDM intake started to decline sharply when this stratum was removed in 0·92 of paddock area (i.e. equivalent to 0·08 of the pasture area remaining un-grazed). It was concluded that the proportion of un-grazed area of the pasture can be used as a grazing management strategy to control forage intake for sugarcane.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Northern Appalachian Basin deposits and associated fossils have served as exemplars for ecological-evolutionary investigations, and as the reference interval for the concept of coordinated stasis. Here, we examine faunal and environmental changes within the uppermost Hamilton and lowermost Genesee Groups of the late Middle Devonian succession of New York State. Dramatic diversity loss, faunal migrations, and ecological restructuring recognized in these strata have been used previously to define the end of the Hamilton ecological-evolutionary subunit, and, furthermore, these strata and corresponding faunal changes represent the type region for the global Taghanic Biocrisis. We present and analyze a new, high-resolution data set of post-Taghanic Genesee fossil assemblages, in which we recognize 11 biofacies corresponding to an onshore-offshore (depth) gradient. The Genesee Fauna shows an unexpectedly high taxonomic similarity to nearshore biofacies of the pre-Taghanic Hamilton Fauna, related to the persistence of siliciclastic-dominated nearshore settings through the Taghanic Biocrisis, whereas the onset of anoxic/dysoxic conditions typified offshore portions of the environmental gradient. The “Nearshore Refugium Model” of Erwin offers a possible explanation for the persistence of taxa through the biocrisis in nearshore settings. This constriction was followed by subsequent expansion of these residual taxa to offshore environments in relatively similar associations, as increased Acadian orogenic activity and resultant delta progradation increased habitable space offshore by decreasing the extent of deeper-water, oxygen-poor settings. Although taxonomic similarity was high between the Hamilton and Genesee Faunas, biofacies structure differed primarily because of tectonically driven physical transformations to the basin and associated biotic turnover. Nevertheless, the combination of high taxonomic persistence of Hamilton nearshore taxa and the introduction of relatively few new taxa in the Genesee Fauna resulted in a taxonomic holdover that was much higher than observed in the original formulation of coordinated stasis.
In the last decades many techniques have been proposed to manufacture thin (<50µm) silicon solar cells. The main issues in manufacturing thin solar cells are the unavailability of a reliable method to produce thin silicon foils with contained material losses (kerf-losses) and the difficulties in handling and processing such fragile foils. A way to solve both issues is to grow an epitaxial foil on top of a weak sintered porous silicon layer. The porous silicon layer is formed by electrochemical etching on a thick silicon substrate and then annealed to close the top surface. This surface is employed as seed layer for the epitaxial growth of a silicon layer which can be partially processed while attached on the substrate that provides mechanical support. Afterward, the foil can be bonded on glass, detached and further processed at module level. The efficiency of the final solar cell will depend on the quality of the epitaxial layer which, in turn, depends on the seed layer smoothness.
Several parameters can be adjusted to change the morphology and, hence, the properties of the porous layer, both in the porous silicon formation and the succeeding thermal treatment. This work focuses on the effect of the parameters that control the porous silicon formation on the structure of the porous silicon layer after annealing and, more specifically, on the roughness of the top surface. The reported analysis shows how the roughness of the seed layer can be reduced to improve the quality of the epitaxial growth.
This Summary for Policymakers presents key findings from the Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation (SREX). The SREX approaches the topic by assessing the scientific literature on issues that range from the relationship between climate change and extreme weather and climate events (‘climate extremes’) to the implications of these events for society and sustainable development. The assessment concerns the interaction of climatic, environmental, and human factors that can lead to impacts and disasters, options for managing the risks posed by impacts and disasters, and the important role that non-climatic factors play in determining impacts. Box SPM.1 defines concepts central to the SREX.
The character and severity of impacts from climate extremes depend not only on the extremes themselves but also on exposure and vulnerability. In this report, adverse impacts are considered disasters when they produce widespread damage and cause severe alterations in the normal functioning of communities or societies. Climate extremes, exposure, and vulnerability are influenced by a wide range of factors, including anthropogenic climate change, natural climate variability, and socioeconomic development (Figure SPM.1). Disaster risk management and adaptation to climate change focus on reducing exposure and vulnerability and increasing resilience to the potential adverse impacts of climate extremes, even though risks cannot fully be eliminated (Figure SPM.2). Although mitigation of climate change is not the focus of this report, adaptation and mitigation can complement each other and together can significantly reduce the risks of climate change. [SYR AR4, 5.3]