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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 report the discovery of a bow-shock pulsar wind nebula (PWN), named Potoroo, and the detection of a young pulsar J1638$-$4713 that powers the nebula. We present a radio continuum study of the PWN based on 20-cm observations obtained from the Australian Square Kilometre Array Pathfinder (ASKAP) and MeerKAT. PSR J1638$-$4713 was identified using Parkes radio telescope observations at frequencies above 3 GHz. The pulsar has the second-highest dispersion measure of all known radio pulsars (1 553 pc cm$^{-3}$), a spin period of 65.74 ms and a spin-down luminosity of $\dot{E}=6.1\times10^{36}$ erg s$^{-1}$. The PWN has a cometary morphology and one of the greatest projected lengths among all the observed pulsar radio tails, measuring over 21 pc for an assumed distance of 10 kpc. The remarkably long tail and atypically steep radio spectral index are attributed to the interplay of a supernova reverse shock and the PWN. The originating supernova remnant is not known so far. We estimated the pulsar kick velocity to be in the range of 1 000–2 000 km s$^{-1}$ for ages between 23 and 10 kyr. The X-ray counterpart found in Chandra data, CXOU J163802.6$-$471358, shows the same tail morphology as the radio source but is shorter by a factor of 10. The peak of the X-ray emission is offset from the peak of the radio total intensity (Stokes $\rm I$) emission by approximately 4.7$^{\prime\prime}$, but coincides well with circularly polarised (Stokes $\rm V$) emission. No infrared counterpart was found.
Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent–child reading in mitigating the effects of screen time.
Methods
We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent–child reading time was a moderator of the link between screen time and brain network topology.
Results
Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent–child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (β = −0.640, p = 0.005).
Conclusion
Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent–child reading in moderating the association between screen time and topological brain restructuring in early childhood.
In preparation for an experiment with a laser-generated intense proton beam at the Laser Fusion Research Center at Mianyang to investigate the 11B(p,α)2α reaction, we performed a measurement at very low proton energy between 140 keV and 172 keV using the high-voltage platform at the Institute of Modern Physics, Lanzhou. The aim of the experiment was to test the ability to use CR-39 track detectors for cross-section measurements and to remeasure the cross-section of this reaction close to the first resonance using the thick target approach. We obtained the cross-section σ = 45.6 ± 12.5 mb near 156 keV. Our result confirms the feasibility of CR-39 type track detector for nuclear reaction measurement also in low-energy regions.
In a recent survey of nematodes associated with tobacco in Shandong, China, the root-lesion nematode Pratylenchus coffeae was identified using a combination of morphology and molecular techniques. This nematode species is a serious parasite that damages a variety of plant species. The model plant benthi, Nicotiana benthamiana, is frequently used to study plant-disease interactions. However, it is not known whether this plant species is a host of P. coffeae. The objectives of this study were to evaluate the parasitism and pathogenicity of five populations of the root-lesion nematode P. coffeae on N. benthamiana.N. benthamiana seedlings with the same growth status were chosen and inoculated with 1,000 nematodes per pot. At 60 days after inoculation, the reproductive factors (Rf = final population densities (Pf)/initial population densities (Pi)) for P. coffeae in the rhizosphere of N. benthamiana were all more than 1, suggesting that N. benthamiana was a good host plant for P. coffeae.Nicotiana. benthamiana infected by P. coffeae showed weak growth, decreased tillering, high root reduction, and noticeable brown spots on the roots. Thus, we determined that the model plant N. benthamiana can be used to study plant-P. coffeae interactions.
Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from specialists of congenital cardiac disease. The aim of this review is to provide a classification, from the perspective of these specialists, based on an understanding of normal and abnormal morphogenesis and anatomy, with emphasis placed on the features of clinical and surgical relevance. We contend that the description of the congenitally malformed aortic root is simplified when approached in a fashion that recognizes the normal root to be made up of 3 leaflets, supported by their own sinuses, with the sinuses themselves separated by the interleaflet triangles. The malformed root, usually found in the setting of 3 sinuses, can also be found with 2 sinuses, and very rarely with 4 sinuses. This permits description of trisinuate, bisinuate, and quadrisinuate variants, respectively. This feature then provides the basis for classification of the anatomical and functional number of leaflets present. By offering standardized terms and definitions, we submit that our classification will be suitable for those working in all cardiac specialties, whether pediatric or adult. It is of equal value in the settings of acquired or congenital cardiac disease. Our recommendations will serve to amend and/or add to the existing International Paediatric and Congenital Cardiac Code, along with the Eleventh iteration of the International Classification of Diseases provided by the World Health Organization.
To evaluate the change in consumption of specific antibiotics in a neonatal intensive care unit after the implementation of an antimicrobial stewardship program (ASP).
Design:
Retrospective cohort study between January 1, 2010, and December 31,2019.
Setting:
The neonatal intensive care unit at British Columbia Women’s Hospital (Vancouver Canada), a tertiary-care center.
Patients:
Admitted neonates prescribed antibiotics.
Methods:
We implemented an ASP with an early implementation phase starting in January 2014 (period 2) and a later phase starting in January 2017 (period 3). Patient demographics were collected, including birth weight, gestational age, history of necrotizing enterocolitis (NEC), and surgical operations from existing databases. Interrupted time-series analysis was used, and comparison of antibiotic days of therapy (DOT) averages were conducted across the preimplementation period (period 1), period 2, and period 3 regarding total patients and subgroups.
Results:
We identified 4,512 infants. There was a significant decrease in DOT from 472 (95% confidence interval [CI], 431–517) in period 1 to 405 (95% CI, 367–446) in period 2 to 313 (95% CI, 280–350) in period 3. We detected a significant decrease in the use of ampicillin, aminoglycosides, cloxacillin, and linezolid but not in vancomycin or cefotaxime. Subgroup analyses of infants <1,500 g and those without NEC or surgery showed decreases in the use of cloxacillin, aminoglycosides, and linezolid.
Conclusions:
The implementation of an ASP was associated with a significant decrease in the overall DOT and use of certain antibiotics. This study presents important targets for ongoing ASP work.
The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.
Student's t test is valid for statistical inference under the normality assumption or asymptotically. By contrast, although the bootstrap t test was proposed in 1993, it is seldom adopted in medical research. We aim to demonstrate that the bootstrap t test outperforms Student's t test under normality in data. Using random data samples from normal distributions, we evaluated the testing performance, in terms of true-positive rate (TPR) and false-positive rate and diagnostic abilities, in terms of the area under the curve (AUC), of the bootstrap t test and Student's t test. We explore the AUC of both tests with varying sample size and coefficient of variation. We compare the testing outcomes using the COVID-19 serial interval (SI) data in Shenzhen and Hong Kong, China, for demonstration. With fixed TPR, the bootstrap t test maintained the equivalent accuracy in TPR, but significantly improved the true-negative rate from the Student's t test. With varying TPR, the diagnostic ability of bootstrap t test outperformed or equivalently performed as Student's t test in terms of the AUC. The equivalent performances are possible but rarely occur in practice. We find that the bootstrap t test outperforms by successfully detecting the difference in COVID-19 SI, which is defined as the time interval between consecutive transmission generations, due to sex and non-pharmaceutical interventions against the Student's t test. We demonstrated that the bootstrap t test outperforms Student's t test, and it is recommended to replace Student's t test in medical data analysis regardless of sample size.
The linear and nonlinear mechanical properties of recombinant protein polymer networks are reviewed, with particular emphasis on how to tune elastic and dissipative behavior through selection of cross-linking strategy. The design strategies used to produce modular recombinant protein polymer networks through chemical or physical cross-linking will be discussed. In particular, we will highlight how key parameters such as polymer concentration, molecular weight, architecture, cross-link density, and association strength influence mechanics of protein polymer networks. Tuning these parameters enables control of viscoelastic properties and formation of materials with applications in tissue engineering, drug delivery, and sustainable self-healing materials.
The onset of magnetic reconnection in space, astrophysical and laboratory plasmas is reviewed discussing results from theory, numerical simulations and observations. After a brief introduction on magnetic reconnection and approach to the question of onset, we first discuss recent theoretical models and numerical simulations, followed by observations of reconnection and its effects in space and astrophysical plasmas from satellites and ground-based detectors, as well as measurements of reconnection in laboratory plasma experiments. Mechanisms allowing reconnection spanning from collisional resistivity to kinetic effects as well as partial ionization are described, providing a description valid over a wide range of plasma parameters, and therefore applicable in principle to many different astrophysical and laboratory environments. Finally, we summarize the implications of reconnection onset physics for plasma dynamics throughout the Universe and illustrate how capturing the dynamics correctly is important to understanding particle acceleration. The goal of this review is to give a view on the present status of this topic and future interesting investigations, offering a unified approach.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The butterfly plastic zone theory based on Mohr Coulomb criterion has been widely used in coal mine production. In order to verify the universality of the theory, it is necessary to compare the distribution of plastic zone under different strength criteria. Based on the elastic-plastic mechanics, the principal stress distribution function around the circular tunnel is deduced in the paper, and the boundary and radius of the plastic zone under different strength criteria are calculated. The results show that the change laws of the plastic zone around the circular tunnel under different strength criteria has the following commonness: firstly, with the increase of the lateral pressure coefficient, the shape of the plastic zone presents the change laws of “circle ellipse butterfly”; Secondly, with the increase of the lateral pressure coefficient, the radius of the plastic zone is exponential distribution, while the characteristic value is different when the radius of the plastic zone is infinite. At same time, it shows that the butterfly plastic zone has a low sensitivity dependence on the strength criterion, no matter which strength criterion is adopted, and the butterfly plastic zone will inevitably appear in the surrounding rock mass of circular tunnel in the high deviator stress environment; The plastic zone with butterfly shape is highly sensitive to the stress change, and the small stress change may promote the expansion of the plastic zone. This result is significant for us to understand and prevent rock engineering disasters and accidents.
‘Recurrence’ of coronavirus disease 2019 (COVID-19) has triggered numerous discussions of scholars at home and abroad. A total of 44 recurrent cases of COVID-19 and 32 control cases admitted from 11 February to 29 March 2020 to Guanggu Campus of Tongji Hospital affiliated to Tongji Medical College Huazhong University of Science and Technology were enrolled in this study. All the 44 recurrent cases were classified as mild to moderate when the patients were admitted for the second time. The gender and mean age in both cases (recurrent and control) were similar. At least one concomitant disease was observed in 52.27% recurrent cases and 34.38% control cases. The most prevalent comorbidity among them was hypertension. Fever and cough being the most prevalent clinical symptoms in both cases. On comparing both the cases, recurrent cases had markedly elevated concentrations of alanine aminotransferase (ALT) (P = 0.020) and aspartate aminotransferase (AST) (P = 0.007). Moreover, subgroup analysis showed mild to moderate abnormal concentrations of ALT and AST in recurrent cases. The elevated concentrations of ALT and AST may be recognised as predictive markers for the risk of ‘recurrence’ of COVID-19, which may provide insights into the prevention and control of COVID-19 in the future.
To conduct international comparisons of self-reports, collateral reports, and cross-informant agreement regarding older adult psychopathology.
Participants:
We compared self-ratings of problems (e.g. I cry a lot) and personal strengths (e.g. I like to help others) for 10,686 adults aged 60–102 years from 19 societies and collateral ratings for 7,065 of these adults from 12 societies.
Measurements:
Data were obtained via the Older Adult Self-Report (OASR) and the Older Adult Behavior Checklist (OABCL; Achenbach et al., 2004).
Results:
Cronbach’s alphas were .76 (OASR) and .80 (OABCL) averaged across societies. Across societies, 27 of the 30 problem items with the highest mean ratings and 28 of the 30 items with the lowest mean ratings were the same on the OASR and the OABCL. Q correlations between the means of the 0–1–2 ratings for the 113 problem items averaged across all pairs of societies yielded means of .77 (OASR) and .78 (OABCL). For the OASR and OABCL, respectively, analyses of variance (ANOVAs) yielded effect sizes (ESs) for society of 15% and 18% for Total Problems and 42% and 31% for Personal Strengths, respectively. For 5,584 cross-informant dyads in 12 societies, cross-informant correlations averaged across societies were .68 for Total Problems and .58 for Personal Strengths. Mixed-model ANOVAs yielded large effects for society on both Total Problems (ES = 17%) and Personal Strengths (ES = 36%).
Conclusions:
The OASR and OABCL are efficient, low-cost, easily administered mental health assessments that can be used internationally to screen for many problems and strengths.
A study on ${Re} =2000$ and 4000 vortex rings colliding with V-walls with included angles of $\theta =30^{\circ }$ to 120$^{\circ }$ has been conducted. Along the valley plane, higher Reynolds numbers and/or included angles of $\theta \leqslant 60^{\circ }$ lead to secondary/tertiary vortex-ring cores leapfrogging past the primary vortex-ring cores. The boundary layers upstream of the latter separate and the secondary/tertiary vortex-ring cores pair up with these wall-separated vortices to form small daisy-chained vortex dipoles. Along the orthogonal plane, primary vortex-ring cores grow bulbous and incoherent after collisions, especially as the included angle reduces. Secondary and tertiary vortex-ring core formations along this plane also lag those along the valley plane, indicating that they form by propagating from the wall surfaces to the orthogonal plane as the primary vortex ring gradually comes into contact with the entire V-wall. Circulation results show significant variations between the valley and orthogonal plane, and reinforce the notion that the collision behaviour for $\theta \leqslant 60^{\circ }$ is distinctively different from those at larger included angles. Vortex-core trajectories are compared to those for inclined-wall collisions, and secondary vortex-ring cores are found to initiate earlier for the V-walls, postulated to be a result of the opposing circumferential flows caused by the simultaneous collisions of both primary vortex-ring cores with the V-wall surfaces. These circumferential flows produce a bi-helical flow mode (Lim, Exp. Fluids, vol. 7, issue 7, 1989, pp. 453–463) that sees higher vortex compression levels along the orthogonal plane, which limit vortex stretching along the wall surfaces and produce secondary vortex rings earlier. Lastly, vortex structures and behaviour of the present collisions are compared to those associated with flat/inclined walls and round-cylinder-based collisions for a more systematic understanding of their differences.
Previous work led to the proposal that the precision feeding of a high-concentrate diet may represent a potential method with which to enhance feed efficiency (FE) when rearing dairy heifers. However, the physiological and metabolic mechanisms underlying this approach remain unclear. This study used metabolomics analysis to investigate the changes in plasma metabolites of heifers precision-fed diets containing a wide range of forage to concentrate ratios. Twenty-four half-sib Holstein heifers, with a similar body condition, were randomly assigned into four groups and precision fed with diets containing different proportions of concentrate (20%, 40%, 60% and 80% based on DM). After 28 days of feeding, blood samples were collected 6 h after morning feeding and gas chromatography time-of-flight/MS was used to analyze the plasma samples. Parameters of oxidative status were also determined in the plasma. The FE (after being corrected for gut fill) increased linearly (P < 0.01) with increasing level of dietary concentrate. Significant changes were identified for 38 different metabolites in the plasma of heifers fed different dietary forage to concentrate ratios. The main pathways showing alterations were clustered into those relating to carbohydrate and amino acid metabolism; all of which have been previously associated with FE changes in ruminants. Heifers fed with a high-concentrate diet had higher (P < 0.01) plasma total antioxidant capacity and superoxide dismutase but lower (P ≤ 0.02) hydroxyl radical and hydrogen peroxide than heifers fed with a low-concentrate diet, which might indicate a lower plasma oxidative status in the heifers fed a high-concentrate diet. Thus, heifers fed with a high-concentrate diet had higher FE and antioxidant capacity but a lower plasma oxidative status as well as changed carbohydrate and amino acid metabolism. Our findings provide a better understanding of how forage to concentrate ratios affect FE and metabolism in the precision-fed growing heifers.
Conceptual design, as an early phase of the design process, is known to have the highest impact on determining the innovation level of design results. Although many tools exist to support designers in conceptual design, additional knowledge, especially knowledge related to emerging technologies, is still often needed. In this paper the authors aim to propose a data-driven creative concept generation and evaluation approach to support designers in incorporating emerging technologies in the new product early development stage. The approach is demonstrated by means of an illustrated example.
The conventional repetitive transcranial magnetic stimulation (rTMS) has some inadequate of efficacy weak and inadequate for the treatment of depression, easy symptomatic recurrence when stop the treatment. Ours invented the device of sleep electroencephalogram-modulated rTMS (SEM-rTMS) were safe and effective by proved of the animal experiments and clinical pre-test for the treatment of depression. The purpose of this study was to examine the efficacy and safety of SEM-rTMS for the treatment of depression.
Methods
After 7 days without psychoactive medication, 164 patients with clinically defined depression, were randomly assigned to receive SEM-rTMS (N = 57), conventional rTMS (C-rTMS (N = 55), or sham-rTMS (N = 52) for 30 minutes/time/day for 10 days. Before and after scores on the 24-item Hamilton rating scale for depression (HAMD-24) and the clinical outcome at the 10th-day of therapy for all subjects were analyzed.
Results
Twenty two cases in the SEM-rTMS group improved mood as compared to 6 in the C-rTMS group and 2 in the sham-rTMS group (c2 = 15.89, p = 0.0004). After completion of the rTMS phase of the protocol, a (51 ± 5) % reduction of HAMD-24 scores from the baseline in the SEM-rTMS group compared with a (34 ± 4)% in the C-rTMS group ((q = 26.09, p = 0.001) and a (14 ± 3)% in Sham-rTMS group (q = 57.53,p = 0.000). The 88% total efficacy ratio in the SEM-rTMS group was significant higher than 68% in the C-rTMS group and 20% in the sham-rTMS group (c2 = 12.01, p = 0.0025). No significant side effects were noted.
Conclusion
It is efficient and safe to treat depression with repetitive transcranial magnetic stimulation. (The registration. No: ChiCTR-TRC-00000438).