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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.
Alligatorweed [Alternanthera philoxeroides (Mart.) Griseb.] is an invasive semiaquatic weed that poses a serious threat to agricultural production and ecological balance worldwide. However, information about genetic factors associated with the adaptation and invasion mechanisms of this species is limited. Screening for appropriate reference genes is important for gene expression and functional analysis research in A. philoxeroides. In this study, 30 candidate genes that showed stable expression in different A. philoxeroides tissues under various treatments in RNA-seq data were chosen to design quantitative real-time PCR (qRT-PCR) primers. After the amplification specificity validation, 25 candidates were selected and further evaluated in a diverse set of A. philoxeroides samples, including leaf, stem, and root tissues under drought, salinity, heat, chilling, five herbicides, and corresponding untreated controls using qRT-PCR. The delta-CT method, geNorm, NormFinder, BestKeeper, and RefFinder algorithms were used to identify stable reference genes from A. philoxeroides samples. Overall, CoA, RFI2, Tubby, SRP19, and V-ATPase were the top five ideal reference genes in all organs and conditions. Tubby and CoA were the most stable reference genes in the leaf/stem; and RFI2, ERprr, and SPR19 were suitable reference genes for the roots. This work provided a foundation for exploring gene expression profiling of A. philoxeroides, especially those adaptation- and invasion-related genes, which may help in management of this invasive weed.
Echinococcus granulosus sensu lato has complex defence mechanisms that protect it from the anti-parasitic immune response for long periods. Echinococcus granulosus cyst fluid (EgCF) is involved in the immune escape. Nevertheless, whether and how EgCF modulates the inflammatory response in macrophages remains poorly understood. Here, real-time polymerase chain reaction and enzyme-linked immunosorbent assay revealed that EgCF could markedly attenuate the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors including tumour necrosis factor-α, interleukin (IL)-12 and IL-6 but increase the expression of IL-10 at mRNA and protein levels in mouse peritoneal macrophages and RAW 264.7 cells. Mechanically, western blotting and immunofluorescence assay showed that EgCF abolished the activation of nuclear factor (NF)-κB p65, p38 mitogen-activated protein kinase (MAPK) and ERK1/2 signalling pathways by LPS stimulation in mouse macrophages. EgCF's anti-inflammatory role was at least partly contributed by promoting proteasomal degradation of the critical adaptor TRAF6. Moreover, the EgCF-promoted anti-inflammatory response and TRAF6 proteasomal degradation were conserved in human THP-1 macrophages. These findings collectively reveal a novel mechanism by which EgCF suppresses inflammatory responses by inhibiting TRAF6 and the downstream activation of NF-κB and MAPK signalling in both human and mouse macrophages, providing new insights into the molecular mechanisms underlying the E. granulosus-induced immune evasion.
Nicotine 3,5-dihydroxybenzoate dihydrate is a nicotine salt and can be used as compositions in tobacco products. X-ray powder diffraction data, unit-cell parameters, and space group for nicotine 3,5-dihydroxybenzoate, C10H15N2⋅C7H5O4⋅2H2O, are reported [a = 8.424(1) Å, b = 13.179(8) Å, c = 8.591(1) Å, α = 90°, β = 102.073(8)°, γ = 90°, unit-cell volume V = 932.765(3) Å3, Z = 2, ρcal = 1.256 g⋅cm−3, and space group P21] at room temperature. All measured lines were indexed and are consistent with the P21 space group.
Narrowband microwave generation with tuneable frequency is demonstrated by illuminating a photoconductive semiconductor switch (PCSS) with a burst-mode fibre laser. The whole system is composed of a high-power linearly polarized burst-mode pulsed fibre laser and a linear-state PCSS. To obtain a high-performance microwave signal, a desired envelope of burst is necessary and a pulse pre-compensation technique is adopted to avoid envelope distortion induced by the gain-saturation effect. Resulting from the technique, homogenous peak power distribution in each burst is ensured. The maximum energy of the laser burst pulse reaches 200 μJ with a burst duration of 100 ns at the average power of 10 W, corresponding to a peak power of 4 kW. When the PCSS is illuminated by the burst-mode fibre laser, narrowband microwave generation with tuneable frequency (0.80–1.12 GHz) is obtained with a power up to 300 W. To the best of the authors’ knowledge, it is the first demonstration of frequency-tuneable narrowband microwave generation based on a fibre laser. The high-power burst-mode fibre laser reported here has great potential for generating high-power arbitrary microwave signals for a great deal of applicable demands such as smart adaptive radar and intelligent high-power microwave systems.
We investigated motor cortical excitability (CE) in unilateral temporal lobe epilepsy (TLE) and its relationship to bilateral tonic-clonic seizure (BTCS) using paired-pulse transcranial magnetic stimulation (TMS).
In this cross-sectional study, we enrolled 46 unilateral TLE patients and 16 age-and sex-matched healthy controls. Resting motor thresholds (RMT); short-interval intracortical inhibition (SICI, GABAA receptor-mediated); facilitation (ICF, glutamatergic-mediated) with interstimulus intervals (ISIs) of 2, 5, 10, and 15 ms; and long-interval intracortical inhibition (LICI, GABAB receptor-mediated) with ISIs of 200–400 ms were measured via paired-pulse TMS. Comparisons were made between controls and patients with TLE, and then among the TLE subgroups (no BTCS, infrequent BTCS and frequent BTCS subgroup).
Compared with controls, TLE patients had higher RMT, lower SICI and higher LICI in both hemispheres, and higher ICF in the ipsilateral hemisphere. In patients with frequent BTCS, cortical hyperexcitability in the ipsilateral hemisphere was found in a parameter-dependent manner (SICI decreased at a stimulation interval of 5 ms, and ICF increased at a stimulation interval of 15 ms) compared with patients with infrequent or no BTCS.
Our results demonstrate that motor cortical hyper-excitability in the ipsilateral hemisphere underlies the epileptogenic network of patients with active BTCS, which is more extensive than those with infrequent or no BTCS.
The thermal expansion coefficient (CTE) is a vital design parameter for reducing the thermal-stress-induced structural failure of electronic chips/devices. At the micro- and nano-scale, the typical size range of the components in chips/devices, the CTEs are probably different from that of the bulk materials, but an easy and accurate measurement method is still lacking. In this paper, we present a simple but effective method for determining linear CTEs of micro-scale materials only using the prevalent nanoindentation system equipped with a heating stage for precise temperature control. By holding a constant force on the sample surface, while heating the sample at a constant rate, we measure two height–temperature curves at two positions, respectively, which are close to each other but at different heights. The linear CTE is obtained by analyzing the difference of height change during heating. This method can be applied to study the size effect or surface effect of CTE of embedded micro-scale structures, aiding the failure analysis and structural design in the semiconductor industry.
The objective of this study was to delineate the characteristics and incidence of congenital heart disease (CHD) in patients with isolated microtia and to determine whether the prevalence of CHD among patients with isolated microtia increases with the severity of microtia.
A total of 804 consecutive patients had a pre-operative colour Doppler echocardiographic examination. A retrospective study was performed with the clinical and imaging data from November, 2017 to January, 2019. The χ2 test was performed to analyse the interaction between isolated microtia and CHD.
With the colour Doppler echocardiographic examination’s data from 804 consecutive isolated microtia patients, we found CHD, including atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus, and others, occurred in 52 of 804 patients (6.5%). Atrial septal defect prevalence in patients with isolated microtia was significantly higher than ventricular septal defect (24/804 versus 11/804, p < 0.05) and patent ductus arteriosus (24/804 versus 2/804, p < 0.001). Ventricular septal defect prevalence in patients with isolated microtia was significantly higher than patent ductus arteriosus (11/804 versus 2/804, p < 0.05). All four types of microtia (concha-type microtia, small concha-type microtia, lobule-type microtia, and anotia) had similar incidences of CHD with no difference in the incidences among these types (p > 0.05 respectively). Furthermore, there was no significant difference in the incidence of the atrial septal defect among the four subtypes (p > 0.05 respectively). Similarly, ventricular septal defect and patent ductus arteriosus also showed no differences (p > 0.05 respectively).
The overall incidences of CHD and three most common CHD subtypes (atrial septal defect, ventricular septal defect, and patent ductus arteriosus) in patients with isolated microtia are higher than general population. The prevalence of CHD among patients with isolated microtia does not increase with the severity of microtia. According to our experience in this study, we suggest colour Doppler echocardiographic imaging should be performed for isolated microtia patients soon after birth if possible. Furthermore, for the plastic surgeon and anaesthesiologist, it is important to take pre-operative colour Doppler echocardiographic images which can help evaluate heart function to ensure the safety of the peri-operative period. Future studies when investigating CHDs associated with isolated microtia could focus on genetic and molecular mechanisms.
To evaluate the effects of dietary Ca intake and Ca supplementation during pregnancy on low birth weight (LBW) and small for gestational age (SGA) infants.
A birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China.
A birth cohort study.
Totally, 9595 pregnant women who came to the hospital for delivery at 20 weeks of gestation or more, and who were 18 years of age or older.
Compared with non-users, Ca supplement users had a reduced risk of LBW infants (OR = 0·77, 95 % CI: 0·63, 0·95) and a reduced risk of nulliparous women giving birth to LBW infants (OR = 0·75, 95 % CI: 0·58, 0·98) (P < 0·05). More specifically, both the use of Ca supplement before conception and during pregnancy (OR = 0·44, 95 % CI: 0·19, 0·99) and during pregnancy only (OR = 0·80, 95 % CI: 0·65, 0·99) had the main effect of reducing risk of nulliparous women giving birth to LBW infants (P < 0·05). There was no association between Ca supplementation and SGA (OR = 0·87, 95 % CI: 0·75, 1·01) (P > 0·05). However, higher dietary Ca intake during pregnancy decreases the risk of both LBW (quartile 2: OR = 0·72, 95 % CI: 0·55, 0·94; quartile 3: OR = 0·68, 95 % CI: 0·50, 0·62) and SGA infants (quartile 2: OR = 0·77, 95 % CI: 0·63, 0·95; quartile 3: OR = 0·71, 95 % CI: 0·57, 0·88, quartile 4: OR = 0·71, 95 % CI: 0·57, 0·88) (P < 0·05).
Ca supplementation and adequate dietary intake of Ca during pregnancy are associated with a decreased risk of LBW infants born to nulliparous women.
Detecting the turbulent/non-turbulent interface is a challenging topic in turbulence research. In the present study, machine learning methods are used to train detectors for identifying turbulent regions in the flow past a circular cylinder. To ensure that the turbulent/non-turbulent interface is independent of the reference frame of coordinates and is physics-informed, we propose to use invariants of tensors appearing in the transport equations of velocity fluctuations, strain-rate tensor and vortical tensor as the input features to identify the flow state. The training samples are chosen from numerical simulation data at two Reynolds numbers,
and 3900. Extreme gradient boosting (XGBoost) is utilized to train the detector, and after training, the detector is applied to identify the flow state at each point of the flow field. The trained detector is found robust in various tests, including the applications to the entire fields at successive snapshots and at a higher Reynolds number
. The objectivity of the detector is verified by changing the input features and the flow region for choosing the turbulent training samples. Compared with the conventional methods, the proposed method based on machine learning shows its novelty in two aspects. First, no threshold value needs to be specified explicitly by the users. Second, machine learning can treat multiple input variables, which reflect different properties of turbulent flows, including the unsteadiness, vortex stretching and three-dimensionality. Owing to these advantages, XGBoost generates a detector that is more robust than those obtained from conventional methods.
A recently developed pneumonia caused by SARS-CoV-2 has quickly spread across the world. Unfortunately, a simplified risk score that could easily be used in primary care or general practice settings has not been developed. The objective of this study is to identify a simplified risk score that could easily be used to quickly triage severe COVID-19 patients. All severe and critical adult patients with laboratory-confirmed COVID-19 on the West campus of Union Hospital, Wuhan, China, from 28 January 2020 to 29 February 2020 were included in this study. Clinical data and laboratory results were obtained. CURB-65 pneumonia score was calculated. Univariate logistic regressions were applied to explore risk factors associated with in-hospital death. We used the receiver operating characteristic curve and multivariate COX-PH model to analyse risk factors for in-hospital death. A total of 74 patients (31 died, 43 survived) were finally included in the study. We observed that compared with survivors, non-survivors were older and illustrated higher respiratory rate, neutrophil-to-lymphocyte ratio, D-dimer and lactate dehydrogenase (LDH), but lower SpO2 as well as impaired liver function, especially synthesis function. CURB-65 showed good performance for predicting in-hospital death (area under curve 0.81, 95% confidence interval (CI) 0.71–0.91). CURB-65 ⩾ 2 may serve as a cut-off value for prediction of in-hospital death in severe patients with COVID-19 (sensitivity 68%, specificity 81%, F1 score 0.7). CURB-65 (hazard ratio (HR) 1.61; 95% CI 1.05–2.46), LDH (HR 1.003; 95% CI 1.001–1.004) and albumin (HR 0.9; 95% CI 0.81–1) were risk factors for in-hospital death in severe patients with COVID-19. Our study indicates CURB-65 may serve as a useful prognostic marker in COVID-19 patients, which could be used to quickly triage severe patients in primary care or general practice settings.
Little is known about poverty trends in people with severe mental illness (SMI) over a long time span, especially under conditions of fast socioeconomic development.
This study aims to unravel changes in household poverty levels among people with SMI in a fast-changing rural community in China.
Two mental health surveys, using ICD-10, were conducted in the same six townships of Xinjin county, Chengdu, China. A total of 711 and 1042 people with SMI identified in 1994 and 2015, respectively, participated in the study. The Foster-Greer-Thorbecke poverty index was adopted to measure the changes in household poverty. These changes were decomposed into effects of growth and equity using a static decomposition method. Factors associated with household poverty in 1994 and 2015 were examined and compared by regression analyses.
The proportion of poor households, as measured by the headcount ratio, increased significantly from 29.8% in 1994 to 39.5% in 2015. Decomposition showed that poverty in households containing people with SMI had worsened because of a redistribution effect. Factors associated with household poverty had also changed during the study period. The patient's age, ability to work and family size were of paramount significance in 2015.
This study shows that the levels of poverty faced by households containing people with SMI has become more pressing with China's fast socioeconomic development. It calls for further integration of mental health recovery and targeted antipoverty interventions for people with SMI as a development priority.
Teenagers are important carriers of Neisseria meningitidis, which is a leading cause of invasive meningococcal disease. In China, the carriage rate and risk factors among teenagers are unclear. The present study presents a retrospective analysis of epidemiological data for N. meningitidis carriage from 2013 to 2017 in Suizhou city, China. The carriage rates were 3.26%, 2.22%, 3.33%, 3.53% and 9.88% for 2013, 2014, 2015, 2016 and 2017, respectively. From 2014 to 2017, the carriage rate in the 15- to 19-year-old age group (teenagers) was the highest and significantly higher than that in remain age groups. Subsequently, a larger scale survey (December 2017) for carriage rate and relative risk factors (population density, time spent in the classroom, gender and antibiotics use) were investigated on the teenagers (15- to 19-year-old age) at the same school. The carriage rate was still high at 33.48% (223/663) and varied greatly from 6.56% to 52.94% in a different class. Population density of the classroom was found to be a significant risk factor for carriage, and 1.4 persons/m2 is recommended as the maximum classroom density. Further, higher male gender ratio and more time spent in the classroom were also significantly associated with higher carriage. Finally, antibiotic use was associated with a significantly lower carriage rate. All the results imply that attention should be paid to the teenagers and various measures can be taken to reduce the N. meningitidis carriage, to prevent and control the outbreak of IMD.
Southern China is affected by multi-stage tectonic activities, with strong fold deformation, complex fault systems and poor shale gas preservation conditions. Here, we used shale samples from the lower Silurian Longmaxi shale in the complex tectonic area of Southern China, to study the relationship between differential structural deformation, and pore structure and adsorption capacity. According to the deformation mechanism of the shale, it is further divided into brittle-slip rheological deformation (BD) and ductile-slip rheological deformation (DD). The results show that all micro-fractures can be observed under scanning electron microscopy in deformed shale samples, but in shale samples with different types of rheological deformation, the micro-fractures have large differences in scale, fracture length and lateral connectivity. The micro-fractures developed in DD shales are small in scale and short in fracture length, but have strong local connectivity. In contrast, brittle minerals are more developed in BD shales, and interlayer shearing has formed micro-fractures with large fracture length and good lateral connectivity, which is beneficial for later fracturing. In these two types of deformed shales, pores in organic matter are rare, and sporadic organic pores have small pore size and poor connectivity. The total pore volume (1.8–2.4 × 10−2 cm3 g–1) of BD shale samples is higher than that of DD shale samples (0.8–1.6 × 10−2 cm3 g–1). There is a positive correlation between total pore volume and quartz content. In addition, the specific surface area (12–18 m2 g–1) of DD shale samples is larger than that of BD shale samples (6–12 m2 g–1).
Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.
The classical taxonomy of fossil invertebrates is based on subjective judgments of morphology, which can cause confusion, because there are no codified standards for the classification of genera. Here, we explore the validity of the genus taxonomy of 75 species and morphospecies of the Follicucullidae, a late Paleozoic family of radiolarians, using a new method, Hayashi's quantification theory II (HQT-II), a general multivariate statistical method for categorical datasets relevant to discriminant analysis. We identify a scheme of 10 genera rather than the currently accepted 3 genera (Follicucullus, Ishigaconus, and Parafollicucullus). As HQT-II cannot incorporate stratigraphic data, a phylogenetic tree of Follicucullidae was reconstructed for 38 species using maximum parsimony. Six lineages emerged, roughly in concordance with the results of HQT-II. Combined with parsimony ancestral state reconstruction, the ancestral group of this family is Haplodiacanthus. Five other groups were discriminated, the Parafollicucullus, Curvalbaillella, Pseudoalbaillella, Longtanella, and Follicucullus–Cariver lineages. The morphological evolution of these lineages comprises a minimum essential list of eight states of four traits. HQT-II is a novel discriminant analytical multivariate method that may be of value in other taxonomic problems of paleobiology.
Most skarns are found near the pluton or in lithologies containing at least some limestone. However, recent research has shown that neither a pluton nor limestone is necessarily required to form a skarn deposit. The newly discovered Bagenheigeqier Pb–Zn skarn deposit is located in NE China. The skarn and Pb–Zn orebodies occur in volcanic lithologies of the Baiyin’gaolao Formation and are controlled by NE–SW-trending faults. The nearest pluton is a granite porphyry, at a distance of 20–250 m from the orebodies. Five paragenetic stages at Bagenheigeqier are recognized: (I) skarn; (II) oxide; (III) early sulphide; (IV) late sulphide; and (V) late quartz–calcite. The fluid inclusions from stages II to V homogenized at temperatures of 402–452, 360–408, 274–319 and 167–212°C, respectively. The hydrogen and oxygen isotope compositions (δ18OH2O, –12.4‰ to +9.3‰; δDH2O, –156.5‰ to –99.1‰) indicate that the ore-fluids were primarily of magmatic origin, with the proportion of meteoric water increasing during the progression of ore formation. Sulphur isotope values (δ34SVCDT, 1.4–5.5‰), lead isotope values (206Pb/204Pb, 18.184–18.717; 207Pb/204Pb, 15.520–15.875; 208Pb/204Pb, 37.991–38.379) and the initial 187Os/188Os ratios of the pyrite (0.307 ± 0.06) suggest that the ore metals were derived from the granite porphyry and Baiyin’gaolao Formation. Re–Os dating of pyrite intergrown with galena and sphalerite yielded a well-constrained isochron age of 151.2 ± 4.7 Ma, which is coeval with the laser ablation – inductively coupled plasma – mass spectrometry zircon U–Pb age of 154 ± 1 Ma for the granite porphyry. The deposit was therefore formed during Late Jurassic time.
Starch content is an important trait in barley. To evaluate the genetic diversity and identify molecular markers of starch content in barley, 40 cultivated barley genotypes collected from different regions, including genotypes whose starch content is at either the high or low end of the spectrum (15), were used in this study. All the genotypes were re-sequenced by the double-digest-restriction associated DNA sequencing method, and a total of 299,103 single-nucleotide polymorphism (SNP) markers were obtained. The genotypes were divided into four sub-populations based on FASTSTRUCTURE, principal component analysis and neighbour-joining tree analysis. All four sub-populations had a high linkage disequilibrium, especially group 3, whose members were recently bred for malting in the Jiangsu coastal area. The starch content of the barley lines was evaluated during three growing seasons (2014–2017), and the average values of starch content across the three growing seasons at the low and high ends were 51.5 and 55.0%, respectively. The starch content was affected by population structure, the barley in group 2 had a low starch content, while the barley in group 4 had a high starch content. Twenty-six SNP markers were identified as being significantly associated with starch content (P ⩽ 0.001) based on the average values across the three growing seasons using the mixed linear model method. These SNP markers were located on chromosomes 1H and 4H, and were considered loci of qSC1-1 and qSC4-1, respectively. The major identified QTLs for starch content are helpful for further research on carbohydrates and for barley breeding.