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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.
The transient shear-induced particle migration of frictional non-Brownian suspensions is studied using particle-resolved simulations. The numerical method – the fictitious domain method – is well suited to heterogeneous flows thanks to a frame-invariant formulation of the subgrid (lubrication) corrections that does not involve the ambient flow (Orsi et al., J. Comput. Phys., vol. 474, 2023, 111823). The paper aims to give an accurate quantitative picture of the mass and momentum balance during the flow. The various assumptions and local constitutive laws that together form the suspension balance model (SBM) are thoroughly examined. To this purpose, the various quantities of interest are locally averaged in space and time, and their profile across the channel is extensively studied, with specific attention to the time evolution of the different contributions, either hydrodynamic in nature or from contact interactions, to the shear and normal stresses. The latter, together with the velocity gradient in the wall-normal direction and the volume fraction profile, yield the local constitutive laws, which are compared with their counterpart obtained in homogeneous shear flow. A fair agreement is observed except in a layering area at the boundaries and at the very centre of the channel. In addition, the main assumption of the SBM, i.e. the local relation between the hydrodynamic force on the particles and the particle flux, is meticulously investigated. The hydrodynamic force is found to be mainly a drag, except in the lower range of the probed volume fractions, where a non-drag contribution is observed.
To measure the effects of health-related food taxes on the environmental impact of consumer food purchases in a virtual supermarket.
Design:
This is a secondary analysis of data from a randomised controlled trial in which participants were randomly assigned to a control condition with regular food prices (n 152), an experimental condition with a sugar-sweetened beverage (SSB) tax (n 131) or an experimental condition with a nutrient profiling tax based on Nutri-Score (n 112). Participants were instructed to undertake their typical weekly grocery shopping for their households. Primary outcome measures were three environmental impact indicators: greenhouse gas (GHG) emissions, land use and blue water use per household per week. Data were analysed using linear regression analyses.
Setting:
Three-dimensional virtual supermarket.
Participants:
Dutch adults (≥ 18 years) who were responsible for grocery shopping in their household (n 395).
Results:
GHG emissions (–7·6 kg CO2-eq; 95 % CI –12·7, –2·5) and land use (–3·9 m2/year; 95 % CI –7·7, –0·2) were lower for the food purchases of participants in the nutrient profiling tax condition than for those in the control condition. Blue water use was not affected by the nutrient profiling tax. Moreover, the SSB tax had no significant effect on any of the environmental impact indicators.
Conclusions:
A nutrient profiling tax based on Nutri-Score reduced the environmental impact of consumer food purchases. An SSB tax did not affect the environmental impact in this study.
Integration of neuropsychological services into multidisciplinary clinics for pediatric patients requiring neurocritical care has previously been shown to improve access to care and promote connection to vital services for children recovering from traumatic brain injuries or other serious insults or infections impacting the brain. As such, the objective of this study is two-fold. First, to explore the unique model of care provided by a neuropsychological inpatient service at the Medical College of Wisconsin/Children’s Wisconsin. Secondly, to describe the benefit of neuropsychology in the Brain Recovery Assessment and Interdisciplinary Needs Clinic (BRAIN) a neurocritical care outpatient follow-up multidisciplinary clinic.
Participants and Methods:
Participants include N =298 pediatric inpatients from a Level 1 Pediatric Trauma center referred to the neuropsychological inpatient consultation service from February 2020 to July 2022. Qualitative methods were used to describe the flow and number of patients initially referred to the neuropsychological inpatient service and then those who followed up in outpatient neuropsychological care prior to and after the implementation of a multi-disciplinary clinic for children admitted to the Neurocritical Care Unit. Rates of follow-up with neuropsychological care were compared pre- and post-establishment of the multidisciplinary clinic. Additional analyses were conducted to explore factors known to impact follow-up with care post-hospitalization (e.g., socioeconomic status, race, ethnicity).
Results:
Prior to the establishment of the BRAIN clinic, approximately 60 to 70% of patients were referred for outpatient neuropsychological follow-up. Approximately 30% of patients referred to the inpatient neuropsychological service following the establishment of the BRAIN clinic were referred for multidisciplinary care, while 20% did not require additional intervention and 50% were referred for outpatient neuropsychological follow-up. Analyses indicated increased follow-up rates with neuropsychological care following the establishment of the BRAIN clinic.
Conclusions:
Integration of neuropsychology into inpatient care and subsequent multidisciplinary settings for pediatric patients with traumatic brain injuries or other serious insults and CNS infections increased access to neuropsychological care. Additional clinical implications will be discussed.
In utero idiopathic constriction of the arterial duct is a rare condition with only a handful reported cases. Ductal aneurysms with thrombus formations on the other hand are significantly more common. We report a case of a term infant who presented with right heart failure due to premature ductal closure and postnatal severe respiratory distress. Subsequent diagnostics revealed paresis of left laryngeal nerve and obstruction of the left pulmonary artery secondary to a ductal aneurysm. Consequently, surgical intervention was considered necessary. Post-operatively, right ventricular function and hoarseness resolved slowly.
OBJECTIVES/GOALS: CTSA Program hubs provide a wide range of research support services (funding, training, consultations, etc.) to individuals and teams. The CTSA Program hub at Columbia University seeks to identify best practices across CTSA hubs in how they facilitate researchers to identify, navigate, and access services at complex academic medical centers. METHODS/STUDY POPULATION: o A landscape analysis across CTSA Program hub websites was conducted during December 2021-February 2022, with the goal of assessing the availability of research navigation services and the ease of accessing and requesting research support services at each hub. Websites of 66 CTSA hubs were accessed and browsed for the following: 1) if a research navigation or concierge service was available; 2) how to request and apply to use common services such as pilot funding, biostatistics, clinical research services; 3) if there was a contact form and/or email address for general inquiries. Binary coding (1=Yes, 2=No) was used to track and summarize if these features were available, and then further classification and observations were noted into the full data set. RESULTS/ANTICIPATED RESULTS: The landscape analysis determined that 68% of CTSA hubs offer a form of research navigation including consultative models (personalized guidance, studios) and web-based models (self-service web portals, graphics, toolkits). Consultative models could be classified into three levels of support ranging from general information sharing to providing scientific expertise to convening more intensive studio sessions. 92% of CTSA hubs have at least 1 system in place for researchers to request services with a majority of hubs using a mix of tools and systems. In addition, 36% of hubs have additional general contact forms and 75% have general email addresses to assist researchers in obtaining more information. DISCUSSION/SIGNIFICANCE: There is a relative lack of data and information on the effectiveness of different research navigation models across the CTSA network, and barriers for researchers to identify services remain (Elworth et al). Our team is planning additional evaluations including interviews with leaders at other CTSA hubs and researchers and trainees at Columbia.
Prenatal closure of foramen ovale without CHD is a rarely reported entity. Therefore, clinical and echocardiographic findings are poorly defined in these patients. We report a patient with prenatal closure of foramen ovale that presented with severe pulmonary hypertension of the newborn and left ventricular failure. Judicious management strategies were utilised to successfully treat both life-threatening conditions.
Effectively addressing public health crises requires dynamic and nimble interdisciplinary collaborations across the translational spectrum, from bench to clinic to community. The Clinical and Translational Science Award (CTSA) Program hubs are uniquely suited to facilitate interdisciplinary collaborations across universities and academic medical centers. This paper describes the activities at the Columbia University CTSA Program hub to address a current public health crisis, the opioid epidemic. Columbia’s CTSA Program hub led a three-phase approach, based on the Conceptual Model of Transdisciplinary Scientific Collaboration as described by Stokols et al.: (1) a university-wide planning and brainstorming phase to identify key leaders across many domains who are influential in addressing the opioid epidemic, (2) a campus-wide and community outreach to identify all interested parties, and (3) ongoing targeted support for collaboration development. Preliminary metrics of success are interdisciplinary collaborations and grant funding. We describe recent examples of how interdisciplinary collaboration, academic-community partnership, and pilot funding contributed to the development and funding of innovative interdisciplinary research, including the New York site of the HEALing Communities initiative. The processes are now being used to support interdisciplinary approaches for other translational public health issues.
Spatially extensive and intense phytoplankton blooms observed off Iberia, in satellite pictures, are driven by significant nutrient supply by upper-ocean vertical mesoscale activity rather than by horizontal advection by coastal upwelling. Productivity of oligotrophic regions is still poorly depicted by discrete instrumental and model data sets. The paleoproductivity reconstructions of these areas represent the mean productivity over long periods, bringing new insights into the total biomass fluxes. Here, we present paleoproductivity records from the oceanic Tore Seamount region, covering the period from 140 to 60 ka. They show higher nutrient supplies during Termination II, Marine Oxygen Isotope Stage (MIS) 4, MIS 6, and warming transitions of the MIS 5 sub-stages. The highest nutrient content (higher productivity) in phase with tracers of bottom-water ventilation (benthic δ13C,231Pa/230Th) establishes a strong linkage with variability of Southern Ocean-sourced waters. Low productivity and ventilation over warm sub-stages of MIS 5 respond instead to North Atlantic Deep Water. Assuming that the Tore Seamount is representative of oligotrophic regions, the glacial-interglacial relationship observed between paleoproductivity and Atlantic Meridional Overturning Circulation strength opens new insights into the importance of estimating the total biomass in these regions. The subtropical gyres might play a considerable role in the carbon cycle over (sub-)glacial-interglacial time scales than previously thought.
Radiocarbon (14C) measurements of foraminifera often provide the only absolute age constraints in marine sediments. However, they are often challenging as their reliability and accuracy can be compromised by reduced availability of adequate sample material. New analytical advances using the MIni CArbon DAting System (MICADAS) allow 14C dating of very small samples, circumventing size limitations inherent to conventional 14C measurements with accelerator mass spectrometry (AMS). Here we use foraminiferal samples and carbonate standard material to assess the reproducibility and precision of MICADAS 14C analyses, quantify contamination biases, and determine foraminiferal 14C blank levels. The reproducibility of conventional 14C ages for our planktic (benthic) foraminiferal samples from gas measurements is 200 (130) yr, and has good precision as illustrated by the agreement between both standards and their reference values as well as between small gas- and larger graphitized foraminiferal samples (within 100±60 yr). We observe a constant contamination bias and slightly higher 14C blanks for foraminifera than for carbonate reference materials, limiting gas (graphite) 14C age determinations for foraminifera from our study sites to ~38 (~42) kyr. Our findings underline the significance of MICADAS gas analyses for 14C on smaller-than-conventional sized foraminiferal samples for paleoclimate reconstructions and dating.
From its original formulation in 1990 the International Trans-Antarctic Scientific Expedition (ITASE) has had as its primary aim the collection and interpretation of a continent-wide array of environmental parameters assembled through the coordinated efforts of scientists from several nations. ITASE offers the ground-based opportunities of traditional-style traverse travel coupled with the modern technology of GPS, crevasse detecting radar, satellite communications and multidisciplinary research. By operating predominantly in the mode of an oversnow traverse, ITASE offers scientists the opportunity to experience the dynamic range of the Antarctic environment. ITASE also offers an important interactive venue for research similar to that afforded by oceanographic research vessels and large polar field camps, without the cost of the former or the lack of mobility of the latter. More importantly, the combination of disciplines represented by ITASE provides a unique, multidimensional (space and time) view of the ice sheet and its history. ITASE has now collected >20 000km of snow radar, recovered more than 240 firn/ice cores (total length 7000 m), remotely penetrated to ~4000m into the ice sheet, and sampled the atmosphere to heights of >20 km.
We investigate and quantify the variability of snow accumulation rate around a medium-depth firn core (160 m) drilled in east Dronning Maud Land, Antarctica (75°00′ S, 15°00’ E; 3470 m h.a.e. (ellipsoidal height)). We present accumulation data from five snow pits and five shallow (20 m) firn cores distributed within a 3.5–7 km distance, retrieved during the 2000/01 Nordic EPICA (European Project for Ice Coring in Antarctica) traverse. Snow accumulation rates estimated for shorter periods show higher spatial variance than for longer periods. Accumulation variability as recorded from the firn cores and snow pits cannot explain all the variation in the ion and isotope time series; other depositional and post-depositional processes need to be accounted for. Through simple statistical analysis we show that there are differences in sensitivity to these processes between the analyzed species. Oxygen isotopes and sulphate are more conservative in their post-depositional behaviour than the more volatile acids, such as nitrate and to some degree chloride and methanesulphonic acid. We discuss the possible causes for the accumulation variability and the implications for the interpretation of ice-core records.
Several lineages of endoparasitoid wasps, which develop inside the body of other insects, have domesticated viruses, used as delivery tools of essential virulence factors for the successful development of their progeny. Virus domestications are major evolutionary transitions in highly diverse parasitoid wasps. Much progress has recently been made to characterize the nature of these ancestrally captured endogenous viruses that have evolved within the wasp genomes. Virus domestication from different viral families occurred at least three times in parasitoid wasps. This evolutionary convergence led to different strategies. Polydnaviruses (PDVs) are viral gene transfer agents and virus-like particles of the wasp Venturia canescens deliver proteins. Here, we take the standpoint of parasitoid wasps to review current knowledge on virus domestications by different parasitoid lineages. Then, based on genomic data from parasitoid wasps, PDVs and exogenous viruses, we discuss the different evolutionary steps required to transform viruses into vehicles for the delivery of the virulence molecules that we observe today. Finally, we discuss how endoparasitoid wasps manipulate host physiology and ensure parasitism success, to highlight the possible advantages of viral domestication as compared with other virulence strategies.
Lateral transport of fine-grained organic carbon particles can complicate the interpretation of paleoclimate records based on organic proxies. Here we investigated the effect of lateral transport on newly developed temperature and soil organic matter proxies, TEX86 and BIT index, respectively, in core MD88–769 recovered from the South East Indian Ridge. Our results show that TEX86 and BIT records in comparison to diatom and foraminifera records were representative for more local climate changes while alkenones and n-alkanes originated from distant areas by oceanic and atmospheric transport, respectively. This suggests that TEX86 and BIT paleoclimate records are primarily influenced by local conditions and less subjected to long-distance lateral transport than other organic proxies in the Southern Ocean.
The enzyme β,β-carotene-15,15′-mono-oxygenase 1 (BCMO1) is responsible for the symmetrical cleavage of β-carotene into retinal. We identified a polymorphism in the promoter of the BCMO1 gene, inducing differences in BCMO1 mRNA levels (high in adenines (AA) and low in guanines (GG)) and colour in chicken breast muscle. The present study was designed to test whether this polymorphism could affect the response to dietary β-carotene. Dietary β-carotene supplementation did not change the effects of the genotypes on breast muscle properties: BCMO1 mRNA levels were lower and xanthophyll contents higher in GG than in AA chickens. Lower vitamin E levels in the plasma and duodenum, plasma cholesterol levels and body weight were also observed in GG than in AA chickens. In both genotypes, dietary β-carotene increased vitamin A storage in the liver; however, it reduced numerous parameters such as SCARB1 (scavenger receptor class B type I) in the duodenum, BCMO1 in the liver, vitamin E levels in the plasma and tissues, xanthophyll contents in the pectoralis major muscle and carcass adiposity. However, several diet × genotype interactions were observed. In the GG genotype, dietary β-carotene increased ISX (intestine-specific homeobox) and decreased BCMO1 mRNA levels in the duodenum, decreased xanthophyll concentrations in the duodenum, liver and plasma, and decreased colour index and HDL-cholesterol concentration in the plasma. Retinol accumulation following dietary β-carotene supplementation was observed in the duodenum of AA chickens only. Therefore, the negative feedback control on β-carotene conversion through ISX appears as functional in the duodenum of GG but not of AA chickens. This could result in a higher availability of β-carotene in the duodenum of GG chickens, reducing the uptake of xanthophylls, liposoluble vitamins and cholesterol.
n-3 PUFA are crucial for health and development. Their effects as regulators of lipid and glucose metabolism are well documented. They also appear to affect protein metabolism, especially by acting on insulin sensitivity. The aim of the present study was to investigate the role of n-3 PUFA, i.e. the precursor α-linolenic acid (ALA) 18 : 3n-3 or long-chain PUFA (LC-PUFA), in chickens, by focusing on their potential function as co-regulators of the insulin anabolic signalling cascade. Ross male broilers were divided into six dietary treatment groups. Diets were isoproteic (22 % crude protein) and isoenergetic (12·54 MJ metabolisable energy/kg) and contained similar lipid levels (6 %) provided by different proportions of various lipid sources: oleic sunflower oil rich in 18 : 1n-9 as control; fish oil rich in LC-PUFA; rapeseed and linseed oils providing ALA. The provision of diets enriched with n-3 PUFA, i.e. rich in LC-PUFA or in the precursor ALA, for 3 weeks improved the growth performance of chickens, whereas that of only the ALA diet enhanced the development of the pectoralis major muscle. At 23 d of age, we studied the insulin sensitivity of the pectoralis major muscle and liver of chickens after an intravenous injection of insulin or saline. The present results indicate that the activation patterns of n-3 PUFA are different in the liver and muscles. An ALA-enriched diet may improve insulin sensitivity in muscles, with greater activation of the insulin-induced 70 kDa ribosomal protein S6 kinase/ribosomal protein S6 pathway involved in the translation of mRNA into proteins, thereby potentially increasing muscle protein synthesis and growth. Our findings provide a basis on which to optimise dietary fatty acid provision in growing animals.