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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.
Many benign and malignant conditions are treated with fertility-threatening medical or surgical therapies. Fertility preservation is a recourse critical to discuss prior to initiation of these therapies. This chapter describes contemporary and future fertility preservation approaches while also exploring barriers in access to their use as well as key decision-making strategies helpful for clinicians caring for patients with a range of medical conditions.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Since the 1980s, the existence of one or more extinction events in the late Ediacaran has been the subject of debate. Discussion surrounding these events has intensified in the last decade, in concert with efforts to understand drivers of global change over the Ediacaran–Cambrian transition and the appearance of the more modern-looking Phanerozoic biosphere. In this paper we review the history of thought and work surrounding late Ediacaran extinctions, with a particular focus on the last 5 years of paleontological, geochemical, and geochronological research. We consider the extent to which key questions have been answered, and pose new questions which will help to characterize drivers of environmental and biotic change. A key challenge for future work will be the calculation of extinction intensities that account for limited sampling, the duration of Ediacaran ‘assemblage’ zones, and the preponderance of taxa restricted to a single ‘assemblage’; without these data, the extent to which Ediacaran bioevents represent genuine mass extinctions comparable to the ‘Big 5’ extinctions of the Phanerozoic remains to be rigorously tested. Lastly, we propose a revised model for drivers of late Ediacaran extinction pulses that builds off recent data and growing consensus within the field. This model is speculative, but does frame testable hypotheses that can be targeted in the next decade of work.
We describe here the early Spathian (Early Triassic) Paris Biota decapod fauna from the western USA basin. This fauna contains two taxa of Aegeridae (Dendobranchiata), namely Anisaeger longirostrus n. sp. and Aeger sp. that are the oldest known representatives of their family, thus extending its temporal range by 5 Myr back into the Early Triassic. This fauna also includes two representatives of Glypheida (Pleocyemata) with Litogaster turnbullensis and Pemphix krumenackeri n. sp., confirming for the former and extending for the latter the temporal ranges of their respective superfamilies back to the Early Triassic. Overall, the Paris Biota decapods are some of the oldest known representatives of Decapoda, filling in an important gap in the evolutionary history of this group, especially during the Triassic that marks the early diversification of this clade. Additionally, we compile and provide overviews for all known Triassic decapods, which leads to the revision of four species of Middle and Late Triassic Aegeridae, and to a revised family assignment of a Middle Triassic Glypheida. Based on this refined dataset, we also investigate decapod diversity throughout the Triassic. We show that the apparent increase in decapod taxonomic richness is probably driven by the heterogeneity of the fossil record and/or sampling effort, and that the decapod alpha diversity is actually relatively high as soon as the Early Triassic and remains rather stable throughout the Triassic.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
${\sim}60\%$
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
This study integrated an experimental medicine approach and a randomized cross-over clinical trial design following CONSORT recommendations to evaluate a cognitive training (CT) intervention for attention deficit hyperactivity disorder (ADHD). The experimental medicine approach was adopted because of documented pathophysiological heterogeneity within the diagnosis of ADHD. The cross-over design was adopted to provide the intervention for all participants and make maximum use of data.
Methods
Children (n = 93, mean age 7.3 +/− 1.1 years) with or sub-threshold for ADHD were randomly assigned to CT exercises over 15 weeks, before or after 15 weeks of treatment-as-usual (TAU). Fifteen dropped out of the CT/TAU group and 12 out of the TAU/CT group, leaving 66 for cross-over analysis. Seven in the CT/TAU group completed CT before dropping out making 73 available for experimental medicine analyses. Attention, response inhibition, and working memory were assessed before and after CT and TAU.
Results
Children were more likely to improve with CT than TAU (27/66 v. 13/66, McNemar p = 0.02). Consistent with the experimental medicine hypotheses, responders improved on all tests of executive function (p = 0.009–0.01) while non-responders improved on none (p = 0.27–0.81). The degree of clinical improvement was predicted by baseline and change scores in focused attention and working memory (p = 0.008). The response rate was higher in inattentive and combined subtypes than hyperactive-impulsive subtype (p = 0.003).
Conclusions
Targeting cognitive dysfunction decreases clinical symptoms in proportion to improvement in cognition. Inattentive and combined subtypes were more likely to respond, consistent with targeted pathology and clinically relevant heterogeneity within ADHD.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
New growth rate estimates for nine species from three genera of New Zealand Crassatellidae (Mollusca: Bivalvia), combined with existing morphometric ontogenetic descriptions, allow identification of heterochronic processes in the evolution of these genera. Both paedomorphosis (progenesis and neoteny) and peramorphosis (hypermorphosis and acceleration) have occurred within the clade. Overall, morphological variability and response to environmental pressure in this nonsiphonate group is restricted by the interplay of anatomical and life habit constraints. Stability in the substrate, predator avoidance, sluggish burrowing speed, and inability to escape by deep burial are suggested as key drivers of, or constraints on, morphological change. Two groups of shell characters are identified: heavy, armored “anchors” and elongate “snorkels,” which combine juvenile and adult traits in shells of different sizes and ages, produced by heterochronic variation in developmental timing. Anchors and snorkels both represent different “solutions” to the problems of life as a nonsiphonate, infaunal bivalve.
Ageing is associated with a prolonged and exaggerated postprandial lipaemia. This study aimed to examine the contribution of alterations in chylomicron synthesis, size and lipid composition to increased lipaemia. Healthy older (60–75 years; n 15) and younger (20–25 years; n 15) subjects consumed a high-fat breakfast. Chylomicron dynamics and fatty acid composition were analysed for 5 h in the postprandial state. Plasma TAG levels were elevated following the meal in the older subjects, relative to younger subjects (P<0·01). For older subjects compared with younger subjects, circulating chylomicron particle size was smaller (P<0·05), with greater apoB content (P<0·05) at all postprandial time points. However, total chylomicron TAG concentration between the groups was unaltered post-meal. Compared with younger subjects, the older subjects exhibited a greater proportion of oleic acid in the TAG and phospholipid (PL) fraction (P<0·05), plus lower proportions of linoleic acid in the TAG fraction of the chylomicrons (P<0·01). Thus, following the ingestion of a high-fat meal, older individuals demonstrate both smaller, more numerous chylomicrons, with a greater total MUFA and lower PUFA contents. These data suggest that the increased postprandial lipaemia of ageing cannot be attributed to increased chylomicron TAG. Rather, ageing is associated with changes in chylomicron particle size, apoB content and fatty acid composition of the chylomicron TAG and PL fractions.
Tall fescue toxicosis adversely affects calving rate and weight gainsreducing returns to cow-calf producers in the south–central United States.This grazing study estimated animal and economic performance implications ofendophyte-infected fescue and calving season. Establishing novelendophyte-infected tall fescue on 25% of pasture acres resulted in improvedcalving rates (87% vs. 70%), weaning weights (532 lbs vs. 513 lbs), andpartial returns per acre ($257 vs. $217). Additionally, fall-calving cowshad higher calving rates (91% vs. 67%), weaning weights (550 lbs vs. 496lbs), and partial returns per acre ($269 vs. $199) than spring calvingcows.
Edited by
Susanna Pietropaolo, Centre National de la Recherche Scientifique (CNRS), Paris,Frans Sluyter, University of Portsmouth,Wim E. Crusio, Centre National de la Recherche Scientifique (CNRS), Paris