The Ubiquitin Specific Protease USP34 promotes ubiquitin signaling at DNA double-strand breaks

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Is better nutrition in childhood in a developing population associated with better cognitive function in later adulthood?: The Guangzhou Biobank Cohort Study

Objective: There is growing evidence that early life exposures, such as childhood socioeconomic status, are related to later adulthood cognition. However, the specific aspect of early conditions underlying this association is not clear. Animal protein intake is positively associated with earlier walking in infants. Dietary supplementation with meat in infants and children in developing countries results in better cognitive function, independent of iron status. Protein energy supplementation with vegetables, milk and sugar (not meat) given from birth to 24 months in developing populations is associated with better cognitive function in early adulthood (mean age 32 years), especially amongst women. Inadequate childhood nutrition is associated with poor short term academic and cognitive outcomes. However, it is not known whether childhood nutrition has life long effects on cognitive function. We examined the association of childhood meat eating with adulthood cognitive function in southern China where the older population lived through significant hardship during their early years. Methods: Multivariable linear regression was used in a crosssectional study of 20,086 Chinese men and women aged >50 years from the Guangzhou Biobank Cohort Study (phases 2 and 3) 2005–8. We assessed the association of childhood meat eating with amnesic-MCI and delayed 10-word recall score. The 10-word recall is a test of new learning ability from the CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) test battery which has been validated as a culturally and educationally sensitive tool for identifying dementia in population based research in developing countries. Amnesic-MCI was defined as a delayed recall score of 3 or less out of 10, corresponding to 1 standard deviation below the mean. Results: Adjusted for age, sex and education, childhood meat eating 1–6 days per week and daily childhood meat eating were associated with a higher 10-word recall score (number of words recalled 50.08 [95% confidence interval50.02 to 0.13] and 0.24 [0.16 to 0.33] respectively) and with lower odds of amnesic-MCI (odds ratio50.80 [95% confidence interval50.72 to 0.89] and 0.79 [0.67 to 0.94] respectively). Additional adjustment for childhood and adulthood socio economic position and current physical activity attenuated these findings, however daily childhood meat eating remained associated with a higher 10-word recall score (0.17 [0.08 to 0.26]. Conclusions: A diet that includes a small amount of daily meat in childhood (after infancy) may have long-term positive effects on cognitive function. If confirmed, these results highlight the importance of adequate childhood nutrition. Alternatively childhood meat eating may reflect a generally more cognitively protective childhood environment and nutrition. Irrespective, these findings also emphasise the childhood and adolescent antecedents of adult disease, with corresponding public health implications for healthy aging. Future research should examine the role of childhood exposures in long term cognitive development and if a role for childhood meat eating is verified, should elucidate the type and quantity of macro and micro nutrients that may be cognitively protective and the biological mechanisms behind these effects, so that preventive strategies can be implemented. Acknowledgements: The University of Hong Kong (HKSAR), Guangzhou Public Health Bureau (China), Guangzhou Science and Technology Bureau (China), The University of Birmingham (UK).published_or_final_versio

Alternative antibody for the detection of CA19-9 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access (R) GI Monitor assay on the UniCel (R) Dxl 800 Immunoassay System

Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access(R) GI Monitor assay (Beckman Coulter) was evaluated on the UniCel(R) Dxl 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access' GI Monitor and Elecsys CA19-9 (R = 0.959, slope = 1.004, intercept +0.17). GI Monitor serum levels were low in healthy individuals (n = 267, median = 6.0 kU/L, 95th percentile = 23.1 kU/L), higher in individuals with various benign diseases (n = 550, medians = 5.8-13.4 kU/L, 95th percentiles = 30.1-195.5 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 8.4-233.8 kU/L, 95th percentiles = 53.7-13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer {[}area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access(R) GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers

A pan-Asian survey of risk perception, attitudes and practices associated with live animal markets.

Key Messages 1. Causal attributions for highly pathogenic avian influenza (HPAI) of the H5N1 virus among live poultry, consumers, retailers and breeders in Vietnam, Thailand, Guangzhou and Hong Kong were studied. 2. Three main themes embodying lay explanation for the causes of H5N1 HPAI emerged: viruses, husbandry-related factors, and vulnerability factors. 3. A deeper understanding of the perceptions of risks, biases, causal attributions, and both the facilitators and barriers to change is needed for planning effective changes in health related behaviour.published_or_final_versio

Life-course origins of social inequalities in adult immune cell markers of inflammation in a developing southern Chinese population: the Guangzhou Biobank Cohort Study

BACKGROUND: Socioeconomic position (SEP) throughout life is associated with cardiovascular disease, though the mechanisms linking these two are unclear. It is also unclear whether there are critical periods in the life course when exposure to better socioeconomic conditions confers advantages or whether SEP exposures accumulate across the whole life course. Inflammation may be a mechanism linking socioeconomic position (SEP) with cardiovascular disease. In a large sample of older residents of Guangzhou, in southern China, we examined the association of life course SEP with inflammation. METHODS: In baseline data on 9,981 adults (>/= 50 years old) from the Guangzhou Biobank Cohort Study (2006-08), we used multivariable linear regression and model fit to assess the associations of life course SEP at four stages (childhood, early adult, late adult and current) with white blood, granulocyte and lymphocyte cell counts. RESULTS: A model including SEP at all four life stages best explained the association of life course SEP with white blood and granulocyte cell count for men and women, with early adult SEP (education) making the largest contribution. A critical period model best explained the association of life course SEP with lymphocyte count, with sex-specific associations. Early adult SEP was negatively associated with lymphocytes for women. CONCLUSIONS: Low SEP throughout life may negatively impact late adult immune-inflammatory status. However, some aspects of immune-inflammatory status may be sensitive to earlier exposures, with sex-specific associations. The findings were compatible with the hypothesis that in a developing population, upregulation of the gonadotropic axis with economic development may obscure the normally protective effects of social advantage for men.published_or_final_versio

Evaluation of moderate alcohol use and cognitive function among men using a mendelian randomization design in the guangzhou biobank cohort study

Observational studies usually show that moderate alcohol use is associated with better cognitive function. Such studies are vulnerable to residual confounding arising from systematic differences between moderate alcohol users and others. A Mendelian randomization study carried out in a suitable population, such as southern Chinese men, in which alcohol use is low to moderate and is influenced by genotype, offers an alternative and superior approach for clarifying the causal effect of moderate alcohol use on cognitive function. The authors used aldehyde dehydrogenase 2 (ALDH2) genotype (AA, GA, or GG) as an instrumental variable in 2-stage least squares analysis to obtain unbiased estimates of the relation of alcohol consumption (measured in alcohol units (10 g ethanol) per day) with cognitive function, assessed from delayed 10-word recall score (n = 4,707) and Mini-Mental State Examination (MMSE) score (n = 2,284), among men from the Guangzhou Biobank Cohort Study (2003-2008). ALHD2 genotype was strongly associated with alcohol consumption, with an F statistic of 71.0 in 2-stage least squares analysis. Alcohol consumption was not associated with delayed 10-word recall score (-0.03 words per alcohol unit, 95% confidence interval:-0.18, 0.13) or MMSE score (0.06 points per alcohol unit, 95% confidence interval:-0.22, 0.34). Moderate alcohol use is unlikely to be cognitively protective. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.postprin

Estimated birth weight and adult cardiovascular risk factors in a developing southern Chinese population: a cross sectional study

Background. Birth weight is negatively associated with cardiovascular diseases and diabetes, but the associations are less well-established in developing populations where birth weight is often unavailable. We studied the association of birth weight and cardiovascular risk, using birth rank as an instrumental variable, in Southern China. Methods. We used published data on birth weight by birth rank from an appropriate population and baseline data from the Guangzhou Biobank Cohort Study phases 2 & 3 (2005-8) to examine the adjusted associations, using instrumental variable analysis, of birth weight with clinically measured cardiovascular risk factors and the metabolic syndrome in older (≥ 50 years) men (n = 5,051) and women (n = 13,907). Results. Estimated birth weight was associated with lower blood pressure (systolic -0.25 mm Hg 95% confidence interval (CI), -0.53 to 0.03 and diastolic -0.33 mm Hg 95% CI -0.48 to -0.18 per standard deviation higher birth weight), but had little association with glucose, lipids, waist-hip ratio, body mass index or the metabolic syndrome, adjusted for age, sex, early environment and number of offspring. Conclusion. Birth weight may impact blood pressure; however associations of birth weight with other cardiovascular risk factors may not be related to foetal exposures, but speculatively could be an historical co-incidence, with corresponding implications for prevention. © 2010 Schooling et al; licensee BioMed Central Ltd.published_or_final_versio

Uncertainty-weighted Multi-tasking for T1ρT_{1\rho} and T2_2 Mapping in the Liver with Self-supervised Learning

Multi-parametric mapping of MRI relaxations in liver has the potential of revealing pathological information of the liver. A self-supervised learning based multi-parametric mapping method is proposed to map T$T_{1\rho}$ and T$_2$ simultaneously, by utilising the relaxation constraint in the learning process. Data noise of different mapping tasks is utilised to make the model uncertainty-aware, which adaptively weight different mapping tasks during learning. The method was examined on a dataset of 51 patients with non-alcoholic fatter liver disease. Results showed that the proposed method can produce comparable parametric maps to the traditional multi-contrast pixel wise fitting method, with a reduced number of images and less computation time. The uncertainty weighting also improves the model performance. It has the potential of accelerating MRI quantitative imaging

Microstructures and resistivity of cuprate/manganite bilayer deposited on SrTiO3 substrate

Thin Yba[SUB2]Cu[SUB3]O[SUB7-δ/La[SUB0.67]Ca[SUB0.33]MnO[SUB3] (YBCO/LCMO) films were grown on SrTiO[SUB3](STO)substrates by magnetron sputtering technique. The microstructures of the bilayers were characterized and a standard four-probe technique was applied to measure the resistivity of the samples. The interdiffusions at the YBCO/LCMO and LCMO/STO interfaces formed two transient layers with the thickness of about 3 and 2 nm, respectively. All the bilayers were well textured along the c axis. At low temperature, the superconductivity can only be observed when the thickness of YBCO is more than 25 nm. When the thickness of YBCO is less than 8 nm, the bilayers show only ferromagnetism. The superconductivity and ferromagnetism perhaps coexist in the bilayer with the YBCO thickness of 12.5 nm. These interesting properties are related to the interaction between spin polarized electrons in the manganites and the cooper pairs in the cuprates. © 2003 American Institute of Physics.published_or_final_versio