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OBJECTIVES/GOALS: We seek to develop a 3D perfusion culture imaging plate for human fecal bacteria co-culture with epithelial cells in a structure that mimics the gut epithelium. We will develop this system for use with patient fecal samples to characterize patient risk of developing cancer. METHODS/STUDY POPULATION: E. coli NC101, a strain that harbors the pks gene island, produces the genotoxin colibactin which causes DNA damage that can lead to colorectal cancer development. The genotoxic ability of this bacterium is dependent upon cell-to-cell contact. Here, we present 3D printed E. coli NC101 and intestinal epithelial cells (IEC-6) in a perfusion imaging plate, enabling visualization of the cytotoxic effects of the bacteria in real time using confocal microscopy, in combination with flow cytometry analysis for cell cycle arrest (a surrogate marker of DNA damage). RESULTS/ANTICIPATED RESULTS: 40,000 IEC-6 cells were 3D printed in a cylindrical layer in our triple well imaging plate. The cells were infected at an MOI of 100 for 18 hours and time lapse images of the infection were recorded by confocal microscopy. The cells were then harvested for analysis by flow cytometry for cell cycle arrest as a measure of DNA damage. Our images and flow cytometry data show that E. coli NC101 co-localizes with IEC-6 cells and causes cell cycle arrest in phase G2 (infected %G2 = 40.1), compared to uninfected cells (%G2 = 24.7, P = 0.034). Mutant strains lacking adhesion protein FimH or the ability to produce colibactin do not cause G2 cell cycle arrest (P = 0.844 and P = 0.644, respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: We are able to recapitulate the DNA damage phenotype of E. coli NC101 in our 3D culture system. We show here that host-microbe interactions leading to cancer can be modeled in our 3D perfusion system, and we will next use patient fecal samples in our culture system.
To estimate the heritability of personality of children by using a twin design method of quantitative genetic analysis. To analysis the influences of family environment on children personality.
EPQ(Eysenck Personality questionnaire) applying on twins children aged 6-16years to evaluate the children personality.
The general questionnaire, PSDQ Parenting Style and Dimension Questionnaire, FAD-GFS(The General Functioning Scale of the MacMaster Family Activity Device), SLE(stressful life events), FSQ(Family Stresses Questionnaire), FLQ(Family Life Questionnaire), EFQ(Everyday Feelings) were used to collect information about family environment from parents. Zygosity was determined by the DNA picked up from cheek mucosa of twins children. Holzinger analysis was employed to estimate the heritability of mental health.
122 pairs(244 children) of twins (103 twin pairs DNA were picked up successfully), including 54 MZ twin pairs and 49 DZ twin pairs.The heritability of personality:N(Extrovision-Introvision):0.71,P(Psychoticism):0.56,L(Lie):0.43,E(Neuroticism):0.07.
In twins family educated-year of father was significantly correlated with EPQ-E,EPQ-N(r = 0.167,0.145);educated-year of mather was significantly correlated with EPQ-N(r = -0.145);the score of FAD-GFS was significantly correlated with EPQ-E(r = - 0.235);FLQ was significantly correlated with EPQ-n(r = 0.356);the score of father authoritative parenting style was significantly correlated with EPQ-p r = -0.196 ;the score of mather authoritative parenting style was significantly correlated with EPQ-e r = 0.230. the score of family cohesion was significantly correlated with EPQ-n(r = 0.198).
Emotional problems were influenced by genetic factors most followed by inattention-hyperactivity problems and total difficulties environment factors play a main role in conduct problems and prosocial degree while peer problems were only influenced by environment factors. Each aspect of family environment, influence children personality and mental differently.
To estimate the heritability of mental health of children by using a twin design method of quantitative genetic analysis. To analysis the influences of family environment on children mental health.
Using cross-sectional design twins aged 6–16 years were recruited. Using SDQ(Strengths and Difficulties Questionnaire)which was examined by parents (>=11)to evaluate the children mental health. The general questionnaire, FADGFS (General Functioning Scale of the MacMaster Family Activity Device), SLE (stressful life events), FSQ (Family Stresses Questionnaire), FLQ (Family Life Questionnaire), EFQ (Everyday Feelings Questionnaire) were used to collect information about family environment from parents. Zygosity was determined by the DNA picked up from cheek mucosa of twins children. Holzinger analysis was employed to estimate the heritability of mental health.
122 pairs of twins (103 pairs DNA were picked up successfully, including 54 MZ and 49 DZ twin pairs.Heritability of mental health: emot (emotion): 0.86, hyper (hyperactivity): 0.75, total: 0.61, cond (conduct): 0.4, proso (prosocial): 0.12, peer (peer): −0.97. In twins family the score of FAD-GFS was significantly correlated with proso (r = −0.200), the score of FSQ, EFQ was significantly correlated with total (r = 0.206, −0.304), FLQ(include three factor) was significantly correlated with total, proso (r = − 0.472, 0.389; r = −0.277,.247; r = −0.298,0.364), the score of father authoritative parenting style was significantly correlated with total, proso r = −0.244,0.207 the score of mather authoritative parenting style was significantly correlated with total, proso r = −0.437, 0.342. The score of family cohesion was significantly correlated with total proso (r = −0.315,0.432), the score of family adaptability was significantly correlated with total, proso r = −0.359, 0.357.
Emotional problems were influenced by genetic factors most followed by inattention-hyperactivity problems and total difficulties environment factors play a main role in conduct problems and prosocial degree while peer problems were only influenced by environment factors. Each aspect of family environment influence children mental health differently.
Patients with severe mental disorders in low-resource settings have limited access to services, resulting in overwhelming caregiving burden for families. In extreme cases, this has led to the long-term restraining of patients in their homes. China underwent a nationwide initiative to unlock patients and provide continued treatment. This study aims to quantify household economic burden in families after unlocking and treatment, and to identify factors associated with increased burden due to schizophrenia.
A total of 264 subjects were enrolled from three geographically diverse provinces in 2012. Subjects were patients with schizophrenia who were previously put under restraints and had participated in the ‘unlocking and treatment’ intervention. The primary outcome was the current household economic burden, obtained from past year financial information collected through on-site interview. Patient disease characteristics, treatment, outcomes and family caregiving burden were collected as well. Univariate and multivariate linear regression were used to construct risk factor models for indirect economic burden.
After participating in the intervention, 85% of patients continued to receive mental health services, 70% used medication as prescribed and 80% were never relocked. Family members reported significantly decreased caregiving burden after receiving the intervention. Mean direct and indirect household economic burdens were CNY963 (US$31.7) and CNY11 724 (US$1670) per year, respectively, while family total income was on average CNY12 108 (US$1913) per year. Greater disease severity and poorer patient psychosocial function at time of study were found to be independent factors related to increased indirect burden.
The ‘unlocking and treatment’ intervention has improved the lives of patients and families. Indirect burden due to disease is still a major economic issue that needs to be addressed, potentially through improving treatment and patient functioning. Our findings contribute to the unravelling and eventual elimination of chronic restraining of mentally ill patients in low-resource settings.
To characterise the dissemination patterns of uropathogenic Escherichia coli (UPEC) in a community, we conducted a study utilising molecular and fundamental descriptive epidemiology. The subjects, consisted of women having community-acquired acute urinary tract infection (UTI), were enrolled in the study from 2011 to 2012. UPEC isolates were subjected to antibacterial-susceptibility testing, O serogrouping, phylotyping, multilocus-sequence typing with phylogenetic-tree analysis and pulsed-field-gel electrophoresis (PFGE). From the 209 unique positive urinary samples 166 UPEC were isolated, of which 129 were fully susceptible to the tested antibiotics. Of the 53 sequence types (STs), the four most prevalent STs (ST95, ST131, ST73 and ST357) accounted for 60% of all UPEC strains. Antimicrobial resistance was less frequently observed for ST95 and ST73 than for the others. A majority of rare STs and a few common STs constituted the diversity pattern within the population structure, which was composed of the two phylogenetically distinct clades. Eleven genetically closely related groups were determined by PFGE, which accounted for 42 of the 166 UPEC isolates, without overt geo-temporal clustering. Our results indicate that a few major lineages of UPEC, selected by unidentified factors, are disseminated in this community and contribute to a large fraction of acute UTIs.
General life stress has been associated with altered DNA methylation in individuals of African Ancestry, although the relationship between parenting stress and DNA methylation has not been described. The purpose of this study was to examine the relationship between maternal parenting stress and DNA methylation among African Ancestry mother-child dyads.
We evaluated epigenome-wide DNA methylation relative to parenting stress in 74 mother-child dyads using linear mixed models.
Significant variation in maternal DNA methylation at 95 CpG sites was associated with level of parenting stress. Notably, we identified a change in DNA methylation associated with poly (ADP-ribose) polymerase-1, which plays a key role in stress signaling. We did not identify any significant variation in child DNA methylation related to maternal parenting stress.
However, DNA methylation patterns observed in children mirrored patterns observed in their mothers. The results suggest that differential maternal DNA methylation is associated with higher levels of parenting stress.
Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.
As a disconnection syndrome, schizophrenia has shown impaired resting-state functional connectivity (rsFC) in the orbitofrontal cortex (OFC); however, the OFC is a rather heterogeneous region and the rsFC changes in the OFC subregions remain unknown.
A total of 98 schizophrenia patients and 102 healthy controls underwent resting-state functional MRI using a sensitivity-encoded spiral-in imaging sequence (SENSE-SPIRAL) to reduce susceptibility-induced signal loss and distortion. The OFC subregions were defined according to a previous parcellation study that divided the OFC into the anterior (OFCa), medial (OFCm), posterior (OFCp), intermediate (OFCi), and lateral (OFCl) subregions. The rsFC was compared using two-way repeated-measures ANOVA.
Whether or not global signal regression, compared with healthy controls, schizophrenia patients consistently exhibited decreased rsFC between the left OFCi and the left middle temporal gyrus and the right middle frontal gyrus (MFG), between the right OFCi and the right MFG and the left inferior frontal gyrus, between the right OFCm and the middle cingulate cortex and the left Rolandic operculum. These rsFC changes still remained significant even after cortical atrophy correction.
These findings suggest a selective functional disconnection of the OFC subregions in schizophrenia, and provide more precise information about the functional disconnections of the OFC in this disorder.
At the end of 2013, China reported a countrywide outbreak of measles. From January to May 2014, we investigated the clinical and immunological features of the cases of the outbreak admitted to our hospital. In this study, all 112 inpatients with clinically diagnosed measles were recruited from the 302 Military Hospital of China. The virus was isolated from throat swabs from these patients, and cytokine profiles were examined. By detecting the measles virus of 30 of the 112 patients, we found that this measles outbreak was of the H1 genotype, which is the major strain in China. The rates of complications, specifically pneumonia and liver injury, differed significantly in patients aged <8 months, 8 months to 18 years, and >18 years: pneumonia was more common in children, while liver injury was more common in adults. Pneumonia was a significant independent risk factor affecting measles duration. Compared to healthy subjects, measles patients had fewer CD4+IL-17+, CD4+IFN-γ+, and CD8+IFN-γ+ cells in both the acute and recovery phases. In contrast, measles patients in the acute phase had more CD8+IL-22+ cells than those in recovery or healthy subjects. We recommend that future studies focus on the age-related distribution of pneumonia and liver injury as measles-related complications as well as the association between immunological markers and measles prognosis.
Epidemiological evidence regarding the association between carbohydrate intake, glycaemic load (GL) and glycaemic index (GI) and risk of ovarian cancer has been mixed. Little is known about their impact on ovarian cancer risk in African-American women. Associations between carbohydrate quantity and quality and ovarian cancer risk were investigated among 406 cases and 609 controls using data from the African American Cancer Epidemiology Study (AACES). AACES is an ongoing population-based case–control study of ovarian cancer in African-Americans in the USA. Cases were identified through rapid case ascertainment and age- and site-matched controls were identified by random-digit dialling. Dietary information over the year preceding diagnosis or the reference date was obtained using a FFQ. Multivariable logistic regression models were used to estimate odds ratios and 95 % CI adjusted for covariates. The OR comparing the highest quartile of total carbohydrate intake and total sugar intake v. the lowest quartile were 1·57 (95 % CI 1·08, 2·28; Ptrend=0·03) and 1·61 (95 % CI 1·12, 2·30; Ptrend<0·01), respectively. A suggestion of an inverse association was found for fibre intake. Higher GL was positively associated with the risk of ovarian cancer (OR 1·18 for each 10 units/4184 kJ (1000 kcal); 95 % CI 1·04, 1·33). No associations were observed for starch or GI. Our findings suggest that high intake of total sugars and GL are associated with greater risk of ovarian cancer in African-American women.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12·2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1·9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3·0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted.
Three groups of genes, Vrn, Ppd and Eps, control life-cycle duration in wheat (Triticum aestivum L.). The duration of a developmental phase between two stages is important for freezing resistance, heading time, anthesis and ripening date as well as yield component generation. The aim of the current study was to assess the effect of Vrn-D1 on wheat development. The vernalization genes Vrn-A1, -B1, -D1, -B3, photoperiod gene Ppd-1 and candidate genes Mot1 and FtsH4 for Eps in ‘G883’, ‘Pumai 9’ and their offspring, a group of sister lines (SLs) derived from an advanced generation, were genotyped using specific molecular markers. All detected loci were the same in the SLs and their parents except the Vrn-D1 locus. Three developmental traits, spike differentiation process, heading date and final leaf number on the main stem, were characterized in three sowing date treatments in the field. When temperatures increased, cultivars/lines carrying the dominant Vrn-D1 gene entered each spike differentiation process faster than those with the recessive vrn-D1 in the same sowing date treatment. Lines carrying Vrn-D1 had smaller final leaf number on the main stem than those with vrn-D1, and the heading dates of the former were earlier than those of the latter, especially in the fourth treatment, sown on 23 February 2012. These data suggest that Vrn-D1 confers a spring habit on wheat and the vrn-D1 confers a cold, hardy winter habit. The Vrn-D1 alleles play very important roles in semi-winter and tender spring wheat cultivars, especially in warm weather in Henan, China. Regulating developmental traits by tracing Vrn-D1 and getting an ideal combination of Vrn alleles to accommodate different wheat zones is a key role for future wheat molecular breeding.
We investigated the prevalence of β-lactamase genes and plasmid-mediated quinolone resistance (PMQR) determinants in 51 carbapenem-resistant Enterobacteriaceae (CRE) from five teaching hospitals in central China. The prevalence of carbapenem resistance in Enterobacteriaceae was 1·0% (51/5012). Of 51 CRE, 31 (60·8%) isolates were positive for one tested carbapenemase gene, while 10 (19·6%) were simultaneously positive for two tested carbapenemase genes. The positive rates of blaKPC-2, blaNDM-1, blaIMP-4, blaIMP-26 and blaIMP-8 were 54·9%, 17·6%, 11·8%, 11·8% and 3·9%, respectively. Of 10 CRE with two carbapenemase genes, three, five, one and one were positive for blaKPC-2 and blaIMP-4, blaKPC-2 and blaIMP-26, blaKPC-2 and blaIMP-8, and blaKPC-2 and blaNDM-1, respectively. Eight of nine blaNDM-1-positive isolates lacked carbapenemases by the modified Hodge test, while 27/28 isolates harbouring blaKPC-2 were positive for carbapenemases determined by this test; 41·2% of the CRE-positive isolates also harboured ESBL genes in various combinations (three and two positive for blaKPC-2 also carried blaDHA-1 and blaCMY-2). The positive rates of qnrS1, qnrA1, qnrB and aac-(6/)-Ib-cr in CRE were 25·5%, 9·8%, 23·5% and 15·7%, respectively. In particular, 7/9 isolates harbouring blaNDM-1 were positive for these quinolone resistance genes, of which five carried qnrS1 and two carried qnrS1 and qnrB4. All but two of 29 Klebsiella pneumoniae isolates were grouped into 20 clonal clusters by PFGE, with the predominant cluster accounting for four blaKPC-2-positive isolates distributed in the same hospital. We conclude that there is a high prevalence of blaNDM-1 and PMQR determinants in CRE isolates in central China. Multiple resistance determinants in various combinations co-exist in these strains and we report for the first time the co-existence of blaKPC-2 and blaIMP-26 in a strain of Klebsiella oxytoca.
An adaptive algorithm is presented for the wavelength calibration of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST). The new algorithm can identify emission lines of calibration lamp without manual interaction and then fit relationship between the pixel positions and the wavelengths by utilizing a polynomial function. In this study, experiments are performed both on the actual data observed by LAMOST and the simulated data to analyze the accuracy and the robustness.The experimental results show that the proposed automatic algorithm can perform the lines identification exactly and acquire the wavelength solution accurately. Thus, an applicable approach is provided for the wavelength calibration of LAMOST.
We investigated the virulence gene carriage and molecular type characteristics of Staphylococcus aureus isolates from bloodstream infections (BSIs) and skin and soft tissue infections (SSTIs) in children. A total of 71 isolates, 16 of which were methicillin-resistant S. aureus (MRSA), were investigated by PCR for virulence-associated gene profiles, sequence type and spa type. This revealed that 76·7% and 53·7% of the SSTI and BSI isolates, respectively, exhibited simultaneous carriage of ⩾10 virulence genes. Compared to BSI isolates, carriage rates for hla, hlb, cna, clfA, seb, sec and pvl genes were significantly higher in SSTI isolates. By contrast, carriage of eta, etb and sea was significantly higher for BSI isolates. Thirty-four sequence types (STs) and 36 spa types were identified in the 71 isolates and included 14 novel STs and four novel spa types. ST59-MRSA-IV/V-t437 was the most common clone in the MRSA isolates. We concluded that virulence determinants are widely distributed in isolates of S. aureus strains from children with BSIs and SSTIs, with an unexpectedly high rate in SSTI isolates. Future profiling of S. aureus virulence determinants may allow the prediction of severity and outcome for children with these infections.
In order to investigate the dynamics of Septin4 (Sept4) expression and its function in the formation of fibrotic livers in mice infected with Schistosoma japonicum, we constructed the mouse model of S. japonicum egg-induced liver fibrosis for 24 weeks. Immunohistochemical staining, qRT-PCR and Western blot were used to detect the expression of Sept4 and α-smooth muscle actin (α-SMA). We found Sept4 localized in the perisinusoidal space where hepatic stellate cells (HSCs) distribute in the periphery of circumoval granulomas and the portal venule. The expression of Sept4 and α-SMA had a similar significant tendency of an up-regulation to a peak at 12 weeks post-infection (p.i.) followed by a down-regulation. At 24 weeks p.i. both were at a low level. These results suggest that Sept4 and α-SMA may interact together in HSCs. Based on this evidence, we hypothesize that Sept4 seems to be involved in the formation of inflammatory granulomata and subsequent liver fibrosis by regulating HSCs activation.
The unit-cell parameters of andalusite and sillimanite have been measured by high-T powder X-ray diffraction up to 1000°C at ambient pressure. Within the temperature range investigated, all the unit-cell parameters varied smoothly, indicating no phase transition. The volume-temperature data were fitted with a polynomial expression for the thermal expansion coefficient (αT = a0 + a1T + a2T-2). yielding a0 = 2.55(2) × 10–5K–1, al = 0 and a2 = 0 for andalusite, and a0 = 1.40(4) × 10–5K–1a1 = 7.1(8) × 10–9K–2 and a2 = 0 for sillimanite. Using the new thermal expansion data determined in the present study and compressional data from the literature, the P-T phase relations of the kyanite-andalusite-sillimanite system were calculated thermodynamically, with the invariant point located at ∼523°C and 3.93 kbar.
Reflective display technologies aim to enable the delivery of dynamic digital content to devices that have the look and feel of ink on paper. We are presenting herein a novel device architecture design and proprietary electrically addressable inks, which enable low power, disruptive, print-like full color reflective display that can exceed the chromaticity represented by the Specifications for Newsprint Advertising Production (SNAP) standard. We are approaching the challenge of generating bright high-quality reflective color images from the perspective of printing by stacking electro-optic layers of subtractive colorants to address every available color at every location. Using in-plane optical effects, our novel media technology provides fast switching between clear and color states. Thin, flexible electronic media based on this technology has been fabricated by imprinting three-dimensional micro-scale structures with a continuous roll-to-roll (R2R) manufacturing platform. HP’s combination of novel device architecture, proprietary inks, and R2R manufacturing platform enables the required attributes for electronic media such as flexibility, robustness, low power, transparency, print-quality color, and scalability at low cost. The structure property relationship of surfactants has been carried out; their impact on performance of display devices has been studied. These results have been applied to improve the performance of electronic inks. We have demonstrated 3-layer stacked segmented reflective display prototypes, as well as pixelated stacked color reflective display prototypes. The innovations described in this paper are applicable to electronic skins for customizable electronic surfaces and are currently being developed further for electronic paper and signage markets.