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OBJECTIVES/GOALS: Utilize polymer-based fiber scaffolds and machine learning methods applied to patient biomarker data to enhance and personalize T cell expansion and production for T cell therapy in chronic lymphocytic leukemia. METHODS/STUDY POPULATION: Scaffolds are 1) generated from a co-polymer blend of PDMS and PCL with controlled fiber diameters and pore size, 2) coated with activating antibodies to CD3 and CD28, and 3) used to stimulate T cells from both healthy donors and CLL patients. CLL patients have pre-annotated mutation burdens and clinical biomarkers. T cell populations will be analyzed for exhaustion markers and phenotypes before, during, and after expansion. Cell functionality will be measured by cytokine secretion, cell cycle analysis, and fold expansion, with respect to platform parameters, and analyzed with inputs of disease markers and exhaustion profile of isolated T cells using regression and random forest classifiers. RESULTS/ANTICIPATED RESULTS: We previously showed that engineering the mechanical rigidity of activating substrates can enhance and rescue T cell expansion from exhausted populations. Now we aim to study a broader range of compositions and geometry of scaffolds with respect to capacity to expand CLL T cells. Preliminary data with fiber diameters ranging from 300 nm to 6 um confirm the effect of geometry in modulating expansion. A biorepository of T cells from 80 CLL patients have been isolated concurrently. Anticipated results include correlating exhaustion profile of T cells with clinical biomarkers and identifying markers associated with expansion on panel of platform parameters. DISCUSSION/SIGNIFICANCE OF IMPACT: T cell therapy has shown particular promise in treating blood cancers, yet significant percentage of T cells isolated from patients undergoing treatments are unresponsive to activation. A powerful tool is to predict if and how patient T cells can be robustly expanded on a personalized approach.
rs10761482 in ANK3 gene showed a significant association with schizophrenia in a genome-wide association study (GWAS). Another marker rs10994336 in ANK3 with the risk of bipolar disorder (BD) which might have more genetic overlap with schizophrenia, had been reported in two meta-analyses of GWAS. In this study, we investigated the association between ANK3 polymorphisms and the susceptibility of schizophrenia in Chinese Han population.
Population-based (schizophrenia patients = 516 and controls = 400) and family based (trios of early onset schizophrenia= 81) study was performed through genotyping the most promising makers rs10761482, rs10994336, and two missenses rs3808942 and rs3808943 near promoter of ANK3. Particularly, we conducted an association analysis for the combined case-control and family samples.
Our population-based study replicated the association between rs10761482 (P = 0.0268 with C allele) and schizophrenia, and detected a novel association with rs10994336 (P = 4.0 × 10−4 with T allele). Haplotype analysis revealed the higher frequencies of C-T, and T-C (rs10761482–10994336) in the cases than controls (P = 0.0032 and P = 0.0012, respectively). In the family study, the C allele of rs10761482 (P = 0.0940) and T allele of rs10994336 (P = 0.0832) were slightly over-transmitted, and T-C was significantly associated with schizophrenia (P = 0.0304). The results from the combined samples analysis were consistent with independent analysis. rs10761482, rs10994336, C-T, and T-C were significantly associated with schizophrenia (P = 3.3 × 10−6∼3.9 × 10−5), whilst rs3808942 and rs3808943 did not reach normal significance.
Our data strongly support ANK3 gene is a schizophrenia susceptibility gene, and also provide further evidence for the shared susceptibility loci between schizophrenia and BD.
Finding the prediction factors for the risks of post-stroke depression (PSD) is important to stroke survivors. However, most existing studies focused only on general clinical data, which limited the predictive ability. To improve the predictive ability, this study proposed a comprehensive PSD risk prediction model with social psychological factors, neurological, cognitive functional factors and general clinical factors.
The study recruited 188 stroke patients. Patients were diagnosed by DSM-IV criteria. Predictors were collected within a week after stroke. Boosted regression trees (BRT) was used to classify these predictors, and then a predictive model was constructed based on the selected predictors. The receiver operating characteristic (ROC) curve was used to determine the performance of the predictive model .
The risk prediction model was constructed with 6 factors: Body Mass Index (BMI), cerebral infraction history (CI), Social Support Rating Scale (SSRS), Eysenck Personality Questionnaire-Neuroticism (EPQ-N), factor 1 of the 20 items Toronto Alexithymia Scale (TAS-F1) and Snaith-Hamilton-Pleasure Scale (SHARPS). In the contribution of risk prediction factors, social psychological factors was more than 0.60. ROC curve of prediction model was 0.826 (p<0.001; 95% CI) and the accuracy of prediction was 0.81 (p<0.001). Transforming the prediction model to a tree diagram, it was convenient to clinic operation.
A PSD risk prediction model with good prediction performance was constructed to achieve diagnose concisely and clearly. The social psychological factors play an important role for diagnosing PSD in the early period.
The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.
The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.
Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.
We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).
Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.
The diagnosis of major depressive disorder (MDD) is symptom based due to the lack of biological biomarker. p11 protein was recently found to be an important factor mediating depression-like states and antidepressant responses. The aim of the study was to assess whether p11 protein in urine can serve as a potential biomarker for major depression, and the relationship of its levels among urine, serum and cerebrospinal fluid (CSF).
We obtained urine samples from 13 drug-free MDD patients and 13 age- and gender-matched healthy controls. We also collected urine, serum and cerebrospinal fluid samples from 13 of fracture patients or cesarean section patients in the spinal anesthesia. The concentrations of p11 protein were measured using ELISA.
In MDD patients, urine levels of p11 protein were all less than the minimum detectable concentration of the ELISA kit. The urine levels of p11 were detectable only in one healthy control. In the spinal anesthesia patients, we can detect p11 concentrations in both serum and urine in only two patients. Besides, levels of p11 were detectable in the serum of one patient and urine of another patient. We were unable to measure CSF levels of p11 in all patients.
Concentrations of p11 protein in the body fluids are very low and unstable. The sensitivity of the current p11 ELISA kit is currently unsatisfactory, requiring the development of an ELISA kit of higher sensitivity to determine whether p11 in body fluids can serve as biomarker for depression.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Bipolar disorder (BD) is a severe psychiatric disorder associated with a high risk of suicide. This meta-analysis examined the prevalence of suicide attempts (SA) in patients with BD and its associated factors.
A systematic literature search was conducted in the PubMed, PsycINFO, EMBASE and Web of Science databases from their inception to 11 June 2018. The prevalence of SA in BD was synthesised using the random-effects model.
The search identified 3451 articles of which 79 studies with 33 719 subjects met the study entry criteria. The lifetime prevalence of SA was 33.9% (95% CI 31.3–36.6%; I2 = 96.4%). Subgroup and meta-regression analyses revealed that the lifetime prevalence of SA was positively associated with female gender, BD-I, BD Not Otherwise Specified and rapid cycling BD subtypes, income level and geographic region.
This meta-analysis confirmed that SA is common in BD and identified a number of factors related to SA. Further efforts are necessary to facilitate the identification and prevention of SA in BD. Long-term use of mood stabilisers coupled with psycho-social interventions should be available to BD patients to reduce the risk of suicidal behaviour.
We present the first images of a coordinated campaign to follow active region NOAA 12709 on 2018 May 13 as part of a joint effort between three observatories (China-Europe). The active region was close to disk center and enclosed a small pore, a tight polarity inversion line and a filament in the chromosphere. The active region was observed with the 1.5-meter GREGOR solar telescope on Tenerife (Spain) with spectropolarimetry using GRIS in the He i 10830 Å spectral range and with HiFI using two broad-band filter channels. In addition, the Lomnicky Stit Observatory (LSO, Slovakia) recorded the same active region with the new Solar Chromospheric Detector (SCD) in spectroscopic mode at Hα 6562 Å. The third ground-based telescope was located at the Fuxian Solar Observatory (China), where the active region was observed with the 1-meter New Vacuum Solar Telescope (NVST), using the Multi-Channel High Resolution Imaging System at Hα 6562 Å. Overlapping images of the active region from all three telescopes will be shown as well as preliminary Doppler line-of-sight (LOS) velocities. The potential of such observations are discussed.
The Chengdu Plain is an agroecosystem that depends on the Dujiangyan (Capital River Weir) for its functioning. This system has been sustained at high levels of productivity for more than two thousand years, experiencing only a few disturbances that have disrupted its functioning. Integrating field and documentary research on ecological, market, and governance factors, this article discusses the remarkable resilience of this system from the late Qing to the present and identifies current threats to its resilience. When the ecology consists of patchy and diverse landscapes, markets allow for adaptation through exchange, and governance includes cross-cutting sources of authority and flexible property regimes, the ecosystem is more resilient—that is, better able to withstand disturbances and maintain its basic functions.
The association between opportunistic infection (OI) and anaemia among HIV-infected patients remains to be studied. We investigated the prevalence and risk factors of anaemia in hospitalised HIV-infected patients to reveal the association between OI and anaemia. We conducted a retrospective study of HIV-positive hospitalised patients from June 2016 to December 2017 in Mengchao Hepatobiliary Hospital of Fujian Medical University. Patients’ information on socio-demographic and clinical characteristics were carefully collected. The comparison of anaemia prevalence between groups was conducted with χ2 test. A logistic regression model was carried out to analyse the predictors of anaemia. The total prevalence of anaemia in hospitalised HIV-infected patients was 55.15%. The prevalence of mild, moderate and severe anaemia was 41.42%, 11.08% and 2.64%, respectively. Predictors independently associated with anaemia were: CD4 counts <50 cells/μl (odds ratio (OR): 6.376, 95% confidence interval (CI) = 1.916–21.215, P = 0.003), CD4 counts 50–199 cells/μl (OR: 6.303, 95% CI = 1.874–21.203, P = 0.003), co-infection with tuberculosis (TB) (OR: 2.703, 95% CI = 1.349–5.414, P = 0.005) or Penicillium marneffei (PM) (OR: 7.162, 95% CI = 3.147–15.299, P < 0.001). In Fujian, China, more than half inpatients with HIV were anaemic, but severe anaemia is infrequent. Lower CD4 counts, co-infection with TB or PM were independent risk factors for anaemia. Chinese HIV patients especially with TB, PM infection and low CD4 level should be routinely detected for anaemia to improve therapy.
Using whole-genome sequence (WGS) data are supposed to be optimal for genome-wide association studies and genomic predictions. However, sequencing thousands of individuals of interest is expensive. Imputation from single nucleotide polymorphisms panels to WGS data is an attractive approach to obtain highly reliable WGS data at low cost. Here, we conducted a genotype imputation study with a combined reference panel in yellow-feather dwarf broiler population. The combined reference panel was assembled by sequencing 24 key individuals of a yellow-feather dwarf broiler population (internal reference panel) and WGS data from 311 chickens in public databases (external reference panel). Three scenarios were investigated to determine how different factors affect the accuracy of imputation from 600 K array data to WGS data, including: genotype imputation with internal, external and combined reference panels; the number of internal reference individuals in the combined reference panel; and different reference sizes and selection strategies of an external reference panel. Results showed that imputation accuracy from 600 K to WGS data were 0.834±0.012, 0.920±0.007 and 0.982±0.003 for the internal, external and combined reference panels, respectively. Increasing the reference size from 50 to 250 improved the accuracy of genotype imputation from 0.848 to 0.974 for the combined reference panel and from 0.647 to 0.917 for the external reference panel. The selection strategies for the external reference panel had no impact on the accuracy of imputation using the combined reference panel. However, if only an external reference panel with reference size >50 was used, the selection strategy of minimizing the average distance to the closest leaf had the greatest imputation accuracy compared with other methods. Generally, using a combined reference panel provided greater imputation accuracy, especially for low-frequency variants. In conclusion, the optimal imputation strategy with a combined reference panel should comprehensively consider genetic diversity of the study population, availability and properties of external reference panels, sequencing and computing costs, and frequency of imputed variants. This work sheds light on how to design and execute genotype imputation with a combined external reference panel in a livestock population.
Suicide attempt (SA), which is one of the strongest predictors of completed suicide, is common in major depressive disorder (MDD) but its prevalence across epidemiological studies has been mixed. The aim of this comprehensive meta-analysis was to examine the pooled prevalence of SA in individuals with MDD.
A systematic literature search was conducted in PubMed, Embase, PsycINFO, Web of Science and Cochrane Library from their commencement date until 27 December 2017. Original studies containing data on prevalence of SA in individuals with MDD were analyzed.
In all, 65 studies with a total of 27 340 individuals with MDD were included. Using the random effects model, the pooled lifetime prevalence of SA was 31% [95% confidence interval (CI) 27–34%], 1-year prevalence was 8% (95% CI 3–14%) and 1-month prevalence was 24% (95% CI 15–34%). Subgroup analyses revealed that the lifetime prevalence of SA was significantly associated with the patient setting, study region and income level, while the 1-month prevalence of SA was associated with only the patient setting.
This meta-analysis confirmed that SA was common in individuals with MDD across the world. Careful screening and appropriate interventions should be implemented for SA in the MDD population.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
This poster reported our spectroscopy of the neutron-star X-ray binary 4U 1728-34, observed with Suzaku in 2010 October. It is classified as an atoll source. Its continuous X-ray spectrum can be fitted by a combination of a multicolour accretion-disk model for the soft energy, plus a power-law model for the hard energy. A broad emission line at 6–7 keV can be fitted well using a simple Gaussian component with an equivalent width of ∼322 eV. However, for this object the presence of that feature is disputed, even though our results from Suzaku do suggest the presence of a broad Fe emission line that is consistent with results from XMM-Newton. Nevertheless, the parameters of the line (the line centroid and the equivalent width) are a little different, but that could be due to a difference in modelling the continuum.
With so many spectroscopic surveys, both past and upcoming, such as SDSS and LAMOST, the number of accessible stellar spectra is continuously increasing. There is therefore a great need for automated procedures that will derive estimates of stellar parameters. Working with spectra from SDSS and LAMOST, we put forward a hybrid approach of Kernel Principal Component Analysis (KPCA) and Support Vector Machine (SVM) to determine the stellar atmospheric parameters effective temperature, surface gravity and metallicity. For stars with both APOGEE and LAMOST spectra, we adopt the LAMOST spectra and APOGEE parameters, and then use KPCA to reduce dimensionality and SVM to measure parameters. Our method provides reliable and precise results; for example, the standard deviation of effective temperature, surface gravity and metallicity for the test sample come to approximately 47–75 K, 0.11–0.15 dex and 0.06–0.075 dex, respectively. The impact of the signal:noise ratio of the observations upon the accuracy of the results is also investigated.
Human cystic echinococcosis is a widespread, chronic, endemic, helminthic zoonosis caused by larval tapeworms of the species Echinococcus granulosus. At present, there is no rational and effective therapy for patients with echinococcosis. The present study evaluated whether the combination of alkaloids from Sophora moorcroftiana seeds (SMSa2) and Bacillus Calmette–Guérin (BCG) was effective in the treatment of experimental echinococcosis. After 20 weeks of secondary infection with protoscoleces, mice were randomly allocated to five groups and treated for 6 weeks by daily intragastric administration of albendazole (ABZ, 100 mg/kg), SMSa2 (100 mg/kg), BCG (abdominal subcutaneous injection at 5 × 106 CFU), SMSa2 + BCG (100 mg/kg SMSa2 and 5 × 106 CFU BCG) or normal saline (untreated group), respectively. The results indicated a significant reduction in the weight of hydatid cysts in the SMSa2 + BCG group compared with the untreated, SMSa2 and BCG groups. The rate of inhibition of hydatid cyst growth in the SMSa2 + BCG group (76.1%) was obviously increased compared with that in the SMSa2 (25.7%) and BCG (26.6%) groups, respectively. Compared with the untreated control, the SMSa2 + BCG group showed a non-significant increase in serum interleukin-4 (IL-4). Furthermore, the serum levels of interferon-γ (IFN-γ) between the untreated and SMSa2 + BCG groups were not statistically different. Therefore, the combination of alkaloids from S. moorcroftiana seeds and BCG can reduce cyst burden and is an effective therapeutic regimen against echinococcosis.
Suicide-related behaviours are common in schizophrenia and are significantly associated with premature death. The objective of this meta-analysis study was to estimate the pooled prevalence of suicide-related behaviours in schizophrenia patients in China.
The relevant literature was searched systematically via the relevant electronic databases (PubMed, Embase, PsycINFO, Chinese National Knowledge Infrastructure, Wanfang Databases and Chinese Biological Medical Literature Database) from their inception until 14 September 2016. Only original studies that reported the prevalence of suicide-related behaviours including suicidal ideation (SI), suicide plan, suicide attempt (SA) and completed suicide were selected.
Nineteen articles met the inclusion criteria and were analysed. The pooled lifetime prevalence of SI and SA were 25.8% (95% CI 14.7–41.1%) and 14.6% (95% CI 9.1–22.8%), respectively. The 1-month prevalence of SI was 22.0% (95% CI 18.2–26.4%). Subgroup analyses of lifetime SI and SA showed that gender, sample size, survey year, study location and source of patients have no significant mediating effects on the results.
Suicide-related behaviours are common in Chinese schizophrenia patients. Due to the high mortality risk, regular screening and effective suicide prevention programmes are warranted.