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Schizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear.
To investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes.
A total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic–neural association, bioinformatics enrichment was explored.
There were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network.
The shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic–neural pathological underpinnings of schizophrenia.
Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).
Materials and Methods
Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.
Most patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.
These data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.
The characteristic traits of maize (Zea mays L.) leaves affect light interception and photosynthesis. Measurement or estimation of individual leaf area has been described using discontinuous equations or bell-shaped functions. However, new maize hybrids show different canopy architecture, such as leaf angle in modern maize which is more upright and ear leaf and adjacent leaves which are longer than older hybrids. The original equations and their parameters, which have been used for older maize hybrids and grown at low plant densities, will not accurately represent modern hybrids. Therefore, the aim of this paper was to develop a new empirical equation that captures vertical leaf distribution. To characterize the vertical leaf profile, we conducted a field experiment in Jilin province, Northeast China from 2015 to 2018. Our new equation for the vertical distribution of leaf profile describes leaf length, width or leaf area as a function of leaf rank, using parameters for the maximum value for leaf length, width or area, the leaf rank at which the maximum value is obtained, and the width of the curve. It thus involves one parameter less than the previously used equations. By analysing the characteristics of this new equation, we identified four key leaf ranks (4, 8, 14 and 20) for which leaf parameter values need to be quantified in order to have a good estimation of leaf length, width and area. Together, the method of leaf area estimation proposed here adds versatility for use in modern maize hybrids and simplifies the field measurements by using the four key leaf ranks to estimate vertical leaf distribution in maize canopy instead of all leaf ranks.
We numerically investigated the phenomenon of non-Gaussian normal diffusion of a Brownian colloidal particle in a periodic array of planar counter-rotating convection rolls. At high Péclet numbers, normal diffusion is observed to occur at all times with non-Gaussian transient statistics. This effect vanishes with increasing the observation time. The displacement distributions decay either slower or faster than a Gaussian function, depending on the flow parameters. The sign of their excess kurtosis is related to the difference between two dynamical time scales, namely, the mean exit time of the particle out of a convection roll and its circulation period inside it.
Loeys–Dietz syndrome is a connective tissue disorder known to cause aggressive aortopathy in paediatric patients, but it is extremely rare for cardiovascular events to present during infancy. We report the first successful aortic repair in a neonate with LDS presenting in extremis with an early onset, massive aortic aneurysm.
Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.
Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.
Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.
Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.
Poroelastic effects have been of great interest in the seismic literature as they have been identified as a major cause of wave attenuation in heterogeneous porous media. The observed attenuation in the seismic wave can be explained in part by energy loss to fluid motion in the pores. On the other hand, it is known that the attenuation is particularly pronounced in stratified structures where the scale of spatial heterogeneity is much smaller than the seismic wavelength. Understanding of poroelastic effects on seismic wave attenuation in heterogeneous porous media has largely relied on numerical experiments. In this work, we present a homogenisation technique to obtain an upscaled viscoelastic model that captures seismic wave attenuation when the sub-seismic scale heterogeneity is periodic. The upscaled viscoelastic model directly relates seismic wave attenuation to the material properties of the heterogeneous structure. We verify our upscaled viscoelastic model against a full poroelastic model in numerical experiments. Our homogenisation technique suggests a new approach for solving coupled equations of motion.
It is important to understand the temporal trend of the paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined the differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. Serial cycle threshold values of SARS-CoV-2 from the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral loads (mean cycle threshold on day 7 of illness 28.6 vs. 36.7, P = 0.02). Peak SARS-CoV-2 viral loads occurred around day 2 of illness in infected children. Although we were unable to directly demonstrate infectivity, the detection of significant amount of virus in the upper airway of asymptomatic children suggest that they have the potential to shed and transmit SARS-CoV-2. Our study highlights the importance of contact tracing and screening for SARS-CoV-2 in children with epidemiological risk factors regardless of their symptom status, in order to improve containment of the virus in the community, including educational settings.
There is a lack of mental health promotion and treatment services targeting HIV-positive men who have sex with men (HIVMSM) in China. The aim of this study was to evaluate the mental health promotion efficacy of an online intervention that combined Three Good Things (TGT) with electronic social networking (TGT-SN) and an intervention that used TGT only (TGT-only), compared with a control group.
We conducted a randomised controlled trial among HIVMSM in Chengdu, China. The participants were randomly assigned to the TGT-SN, TGT-only, and control groups. The participants in the TGT-SN group were divided into five social network groups and asked to post brief messages to the group about three good things that they had experienced and for which they felt grateful. The participants in the TGT-only group were only required to write down their three good things daily without sharing them with others. The control group received information about mental health promotion once a week for a month. The primary outcome was probable depression. Secondary outcomes were anxiety, positive and negative affect, gratitude, happiness and social support. These outcomes were assessed at baseline, 1, 3, 6 and 12 months after the intervention. Repeated-measures analyses were conducted using generalised estimation equations. The study was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-13003252).
Between June 2013 and May 2015, 404 participants were enrolled and randomly assigned to either the TGT-SN (n = 129), TGT-only (n = 139) or control group (n = 136). The main effects of TGT-SN (adjusted odds ratio (aOR) = 0.75, 95% CI 0.52–1.09; p = 0.131) and TGT-only (aOR = 0.83, 95% CI 0.57–1.21; p = 0.332) in reducing depression were statistically non-significant. The participants of the TGT-SN group showed significantly lower anxiety symptoms (aOR = 0.62, 95% CI 0.43–0.89; p = 0.009) and negative affect (β = −1.62, 95% CI 2.98 to −0.26; p = 0.019) over time compared with those of the control group. No significant main effect was found for any secondary outcomes for the TGT-only group.
The novel intervention combining the TGT exercise with electronic social networking was found effective in reducing anxiety and negative affect among HIVMSM.
Determination of antibodies against ToRCH antigens at the beginning of pregnancy allows assessment of both the maternal immune status and the risks to an adverse pregnancy outcome. Age-standardised seroprevalences were determined in sera from 1009 women of childbearing age residing in Mexico, Brazil, Germany, Poland, Turkey or China using a multiparametric immunoblot containing antigen substrates for antibodies against Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex viruses (HSV-1, HSV-2), Bordetella pertussis, Chlamydia trachomatis, parvovirus B19, Treponema pallidum and varicella zoster virus (VZV). Seroprevalences for antibodies against HSV-1 were >90% in samples from Brazil and Turkey, whereas the other four countries showed lower mean age-adjusted seroprevalences (range: 62.5–87.9%). Samples from Brazilian women showed elevated seroprevalences of antibodies against HSV-2 (40.1%), C. trachomatis (46.8%) and B. pertussis (56.6%) compared to the other five countries. Seroprevalences of anti-T. gondii antibodies (0.5%) and anti-parvovirus B19 antibodies (7.5%) were low in samples from Chinese women, compared to the other five countries. Samples from German women revealed a low age-standardised seroprevalence of anti-CMV antibodies (28.8%) compared to the other five countries. These global differences in immune status of women in childbearing age advocate country-specific prophylaxis strategies to avoid infection with ToRCH pathogens.
The Ginzburg–Landau equation (GLE) can phenomenologically model several key features of non-equilibrium systems including those in fluid mechanics. Its validity in real flows, however, remains questionable. Here, we show that the linear GLE can be formulated such that it has the same Wentzel–Kramers–Brillouin (WKB) approximation as for the linear global stability problem in open shear flows. We use the GLE to model the linear global modes of three different wakes and find that it can accurately capture the linear growth rate and frequency to first order in the WKB approximation. Furthermore, we find that it can also provide the shapes of the direct and adjoint eigenvectors and the regions of maximal structural sensitivity. The proposed model requires only the basic flow as input, but gives robust predictions and is computationally inexpensive. As well as opening up new possibilities for GLE-based control strategies, the proposed model makes accurate stability calculations possible, even for some computationally intractable open shear flows.
Critical shortages of personal protective equipment, especially N95 respirators, during the coronavirus disease 2019 (COVID-19) pandemic continues to be a source of concern. Novel methods of N95 filtering face-piece respirator decontamination that can be scaled-up for in-hospital use can help address this concern and keep healthcare workers (HCWs) safe.
A multidisciplinary pragmatic study was conducted to evaluate the use of an ultrasonic room high-level disinfection system (HLDS) that generates aerosolized peracetic acid (PAA) and hydrogen peroxide for decontamination of large numbers of N95 respirators. A cycle duration that consistently achieved disinfection of N95 respirators (defined as ≥6 log10 reductions in bacteriophage MS2 and Geobacillus stearothermophilus spores inoculated onto respirators) was identified. The treated masks were assessed for changes to their hydrophobicity, material structure, strap elasticity, and filtration efficiency. PAA and hydrogen peroxide off-gassing from treated masks were also assessed.
The PAA room HLDS was effective for disinfection of bacteriophage MS2 and G. stearothermophilus spores on respirators in a 2,447 cubic-foot (69.6 cubic-meter) room with an aerosol deployment time of 16 minutes and a dwell time of 32 minutes. The total cycle time was 1 hour and 16 minutes. After 5 treatment cycles, no adverse effects were detected on filtration efficiency, structural integrity, or strap elasticity. There was no detectable off-gassing of PAA and hydrogen peroxide from the treated masks at 20 and 60 minutes after the disinfection cycle, respectively.
The PAA room disinfection system provides a rapidly scalable solution for in-hospital decontamination of large numbers of N95 respirators during the COVID-19 pandemic.
Evaluate associations between orange juice (OJ) consumption and anthropometric parameters.
Prospective cohort study assessing the association between OJ intake and changes in BMI and height-for-age Z-score (HAZ) using mixed linear regression.
Children from the Growing Up Today Study II (n 7301), aged 9–16 years at enrollment.
OJ consumption was positively associated with 2-year change in HAZ in girls (mean (se)): 0·03 (0·01) for non-consumers, 0·03 (0·02) for 1–3 glasses/month, 0·06 (0·01) for 1–6 glasses/week and 0·09 (0·02) for ≥1 glass/d after full adjustment (Ptrend = 0·02). However, OJ consumption was not associated with 2-year change in BMI percentile (kg/m2, mean (se)): –0·44 (0·36) for non-consumers, 0·20 (0·41) for 1–3 glasses/month, –0·04 (0·34) for 1–6 glasses/week and –0·77 (0·62) for ≥1 glass/d in girls, Ptrend = 0·81; –0·94 (0·53) for non-consumers, –1·68 (0·52) for 1–3 glasses/month, –0·81 (0·38) for 1–6 glasses per week and –1·12 (0·61) for ≥1 glass/d in boys, Ptrend = 0·49.
OJ consumption was favourably associated with height growth but unrelated to excess weight gain. OJ may be a useful alternative to whole fruit in the event that whole fruit intake is insufficient.
Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case-fatality rate that is caused by infection with the SFTS virus (SFTSV). Five electronic databases were systematically searched to identify relevant articles published from 1 January 2011 to 1 December 2019. The pooled rates with 95% confidence interval (CI) were calculated by a fixed-effect or random-effect model analysis. The results showed that 92 articles were included in this meta-analysis. For the confirmed SFTS cases, the case-fatality rate was 0.15 (95% CI 0.11, 0.18). Two hundred and ninety-six of 1384 SFTS patients indicated that they had been bitten by ticks and the biting rate was 0.21 (95% CI 0.16, 0.26). The overall pooled seroprevalence of SFTSV antibodies among the healthy population was 0.04 (95% CI 0.03, 0.05). For the overall seroprevalence of SFTSV in animals, the seroprevalence of SFTSV was 0.25 (95% CI 0.20, 0.29). The infection rate of SFTSV in ticks was 0.08 (95% CI 0.05, 0.11). In conclusion, ticks can serve as transmitting vectors of SFTSVs and reservoir hosts. Animals can be infected by tick bites, and as a reservoir host, SFTSV circulates continuously between animals and ticks in nature. Humans are infected by tick bites and direct contact with patient secretions.
In the alloy materials, their mechanical properties mightly rely on the compositions and concentrations of chemical elements. Therefore, looking for the optimum elemental concentration and composition is still a critical issue to design high-performance alloy materials. Traditional alloy designing method via “trial and error” or domain experts’ experiences is barely possible to solve the issue. Here, we propose a “composition-oriented” method combined machine learning to design the Cu–Zn alloys with the high strengths, high ductility, and low friction coefficient. The method of separate training for each attribute label is used to study the effects of elemental concentrations on the mechanical properties of Cu–Zn alloys. Moreover, the elemental concentrations of new Cu–Zn alloys with the good mechanical properties are predicted by machine learning. The current results reveal the vital importance of the “composition-oriented” design method via machine learning for the development of high-performance alloys in a broad range of elemental compositions.
The authors describe Taiwan’s successful strategy in achieving control of coronavirus disease (COVID-19) without economic shutdown, despite the prediction that millions of infections would be imported from travelers returning from Chinese New Year celebrations in Mainland China in early 2020. As of September 2, 2020, Taiwan reports 489 cases, 7 deaths, and no locally acquired COVID-19 cases for the last 135 days (greater than 4 months) in its population of over 23.8 million people. Taiwan created quasi population immunity through the application of established public health principles. These non-pharmaceutical interventions, including public masking and social distancing, coupled with early and aggressive identification, isolation, and contact tracing to inhibit local transmission, represent a model for optimal public health management of COVID-19 and future emerging infectious diseases.
Based on an accurate numerical solution of the kinetic equation using well-resolved spatial and velocity grids, the separation of rarefied gas flow in a microchannel with double rectangular bends is investigated over a wide range of Knudsen and Reynolds numbers. Rarefaction effects are found to play different roles in flow separation (vortex formation) at the concave and convex corners. Flow separations near the concave and convex corners are only observed for a Knudsen number up to
, respectively. With further increase of the Knudsen number, flow separation disappears. Due to the velocity slip at the solid walls, the concave (convex) vortex is suppressed (enhanced), which leads to the late (early) onset of separation of rarefied gas flows with respect to the Reynolds number. The critical Reynolds numbers for the emergence of concave and convex vortices are found to be as low as
, respectively. The slip velocity near the concave (convex) corner is found to increase (decrease) when the Knudsen number increases. An adverse pressure gradient appears near the concave corner for all the examined Knudsen numbers, while for the convex corner it only occurs when the Knudsen number is less than
. Due to the secondary flow and adverse pressure gradient near the rectangular bends, the mass flow rate ratio between the bent and straight channels of the same length is a non-monotonic function of the Knudsen number. Our results clarify the diversified and often contradictory observations reported in the literature about flow rate enhancement and vortex formation in bent microchannels.
We report key learning from the public health management of the first two confirmed cases of COVID-19 identified in the UK. The first case imported, and the second associated with probable person-to-person transmission within the UK. Contact tracing was complex and fast-moving. Potential exposures for both cases were reviewed, and 52 contacts were identified. No further confirmed COVID-19 cases have been linked epidemiologically to these two cases. As steps are made to enhance contact tracing across the UK, the lessons learned from earlier contact tracing during the country's containment phase are particularly important and timely.
The pandemic of coronavirus disease 2019 (COVID-19) has posed serious challenges. It is vitally important to further clarify the epidemiological characteristics of the COVID-19 outbreak for future study and prevention and control measures. Epidemiological characteristics and spatial−temporal analysis were performed based on COVID-19 cases from 21 January 2020 to 1 March 2020 in Shandong Province, and close contacts were traced to construct transmission chains. A total of 758 laboratory-confirmed cases were reported in Shandong. The sex ratio was 1.27: 1 (M: F) and the median age was 42 (interquartile range: 32–55). The high-risk clusters were identified in the central, eastern and southern regions of Shandong from 25 January 2020 to 10 February 2020. We rebuilt 54 transmission chains involving 209 cases, of which 52.2% were family clusters, and three widespread infection chains were elaborated, occurring in Jining, Zaozhuang and Liaocheng, respectively. The geographical and temporal disparity may alert public health agencies to implement specific measures in regions with different risk, and should attach importance on how to avoid household and community transmission.