Nanocrystalline semiconductors: synthesis, properties, and perspectives

The preparation of hollow particles of ZnO by calcination of hydrozincite coated poly(styrene) beads is reported. Synthetic studies have been performed on such polymer/inorganic composite precursors in order to establish the optimum conditions for the preparation of the ZnO particles. The morphological properties of the powders were characterised by optical microscopy and scanning electron microscopy. The micrometric ZnO particles show morphological characteristics related to the template used in their preparation

Bipolar disorder related functional variants in the calcium channel gene family

Bipolar disorder (BD) is a common highly heritable disorder. The calcium channel gene family has been widely implicated in BD aetiology and these genes include CACNA1C, and CACNG4. The association signal for CACNA1C with BD is located in the middle of the third intron of the gene. CACNG4 encodes a transmembrane AMPA receptor regulator that is involved in trafficking AMPA receptors to the neuronal post-synaptic density. High-resolution melting curve (HRM) analysis and whole genome sequencing (WGS) methods were used to identify functional variants in calcium channels genes in the UCL BD cohort. Variants that were predicted to impact gene regulation, transcription or to be damaging to protein structure were genotyped in the larger UCL BD and control cohort. HRM analysis identified 26 calcium channel gene variants. These included two non-synonymous CACNG4 variants that were associated with mental illness (rs371128228, p=1.05x10-4, OR=4.39 and 17:65026851 (C/T), p=5x10-4, OR=9.52). Fluorescent activated cell sorting analysis was used to determine the effect of rs371128228 on trafficking of GluR1 and GluR2 to the cell surface. This analysis demonstrated that the risk allele of rs371128228 significantly decreased cell surface trafficking of GluR1 (p=0.026) but no effect was observed on GluR2 trafficking. WGS analysis of CACNA1C intron 3 identified two BD associated (p=0.015, OR=1.15) variants 105bp apart that were in complete LD. Both variants are predicted to create YY1 transcription factor binding sites. Luciferase reporter assays show a significant decrease in gene expression in the presence of both variants (p=0.004). Protein-DNA complex assays of the CACNA1C variants demonstrate increased nuclear proteins binding affinity for the variant alleles. If these calcium channel variants are confirmed to be important risk factors for BD they could be used as markers for personalised treatment or in the identification of genetic subtypes of BD or other psychiatric illness

Optimal search strategies for detecting cost and economic studies in EMBASE

BACKGROUND: Economic evaluations in the medical literature compare competing diagnosis or treatment methods for their use of resources and their expected outcomes. The best evidence currently available from research regarding both cost and economic comparisons will continue to expand as this type of information becomes more important in today's clinical practice. Researchers and clinicians need quick, reliable ways to access this information. A key source of this type of information is large bibliographic databases such as EMBASE. The objective of this study was to develop search strategies that optimize the retrieval of health costs and economics studies from EMBASE. METHODS: We conducted an analytic survey, comparing hand searches of journals with retrievals from EMBASE for candidate search terms and combinations. 6 research assistants read all issues of 55 journals indexed by EMBASE for the publishing year 2000. We rated all articles using purpose and quality indicators and categorized them into clinically relevant original studies, review articles, general papers, or case reports. The original and review articles were then categorized for purpose (i.e., cost and economics and other clinical topics) and depending on the purpose as 'pass' or 'fail' for methodologic rigor. Candidate search strategies were developed for economic and cost studies, then run in the 55 EMBASE journals, the retrievals being compared with the hand search data. The sensitivity, specificity, precision, and accuracy of the search strategies were calculated. RESULTS: Combinations of search terms for detecting both cost and economic studies attained levels of 100% sensitivity with specificity levels of 92.9% and 92.3% respectively. When maximizing for both sensitivity and specificity, the combination of terms for detecting cost studies (sensitivity) increased 2.2% over the single term but at a slight decrease in specificity of 0.9%. The maximized combination of terms for economic studies saw no change in sensitivity from the single term and only a 0.1% increase in specificity. CONCLUSION: Selected terms have excellent performance in the retrieval of studies of health costs and economics from EMBASE

Socioeconomic status and infectious intestinal disease in the community: a longitudinal study (IID2 study).

Infectious intestinal diseases (IID) are common, affecting around 25% of people in UK each year at an estimated annual cost to the economy, individuals and the NHS of £1.5 billion. While there is evidence of higher IID hospital admissions in more disadvantaged groups, the association between socioeconomic status (SES) and risk of IID remains unclear. This study aims to investigate the relationship between SES and IID in a large community cohort.Longitudinal analysis of a prospective community cohort in the UK following 6836 participants of all ages was undertaken. Hazard ratios for IID by SES were estimated using Cox proportional hazard, adjusting for follow-up time and potential confounding factors.In the fully adjusted analysis, hazard ratio of IID was significantly lower among routine/manual occupations compared with managerial/professional occupations (HR 0.74, 95% CI 0.61-0.90).In this large community cohort, lower SES was associated with lower IID risk. This may be partially explained by the low response rate which varied by SES. However, it may be related to differences in exposure or recognition of IID symptoms by SES. Higher hospital admissions associated with lower SES observed in some studies could relate to more severe consequences, rather than increased infection risk

Hypomethylation of FAM63B in bipolar disorder patients

Bipolar disorder (BD) and schizophrenia (SZ) are known to share common genetic and psychosocial risk factors. A recent epigenome-wide association study performed on blood samples from SZ patients found significant hypomethylation of FAM63B in exon 9. Here, we used iPLEX-based methylation analysis to investigate two CpG sites in FAM63B in blood samples from 459 BD cases and 268 controls. Both sites were significantly hypomethylated in BD cases (lowest p value = 3.94 × 10−8). The methylation levels at the two sites were correlated, and no strong correlation was found with nearby single nucleotide polymorphisms (SNPs), suggesting that methylation differences at these sites are not readably picked up by genome-wide association studies. Overall, FAM63B hypomethylation was found in BD patients, thus replicating the initial finding in SZ patients. This study suggests that FAM63B is a shared epigenetic risk gene for the two disorders

CACNA1C hypermethylation is associated with bipolar disorder

The CACNA1C gene, encoding a subunit of the L-type voltage-gated calcium channel is one of the best-supported susceptibility genes for bipolar disorder (BD). Genome-wide association studies have identified a cluster of non-coding single-nucleotide polymorphisms (SNPs) in intron 3 to be highly associated with BD and schizophrenia. The mechanism by which these SNPs confer risk of BD appears to be through an altered regulation of CACNA1C expression. The role of CACNA1C DNA methylation in BD has not yet been addressed. The aim of this study was to investigate if CACNA1C DNA methylation is altered in BD. First, the methylation status of five CpG islands (CGIs) across CACNA1C in blood from BD subjects (n=40) and healthy controls (n=38) was determined. Four islands were almost completely methylated or completely unmethylated, while one island (CGI 3) in intron 3 displayed intermediate methylation levels. In the main analysis, the methylation status of CGI 3 was analyzed in a larger sample of BD subjects (n=582) and control individuals (n=319). Out of six CpG sites that were investigated, five sites showed significant hypermethylation in cases (lowest P=1.16 × 10(-7) for CpG35). Nearby SNPs were found to influence the methylation level, and we identified rs2238056 in intron 3 as the strongest methylation quantitative trait locus (P=2.6 × 10(-7)) for CpG35. In addition, we found an increased methylation in females, and no difference between bipolar I and II. In conclusion, we find that CACNA1C methylation is associated with BD and suggest that the regulatory effect of the non-coding risk variants involves a shift in DNA methylation

Analysis of ANK3 and CACNA1C variants identified in bipolar disorder whole genome sequence data

Genetic markers in the genes encoding ankyrin 3 (ANK3) and the α-calcium channel subunit (CACNA1C) are associated with bipolar disorder (BP). The associated variants in the CACNA1C gene are mainly within intron 3 of the gene. ANK3 BP-associated variants are in two distinct clusters at the ends of the gene, indicating disease allele heterogeneity

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al

Influence of socio-economic status on Shiga toxin-producing Escherichia coli (STEC) infection incidence, risk factors and clinical features

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group

Evidence for an increase in cosmogenic 10Be during a geomagnetic reversal

Reversals in the geomagnetic field, which occur every few hundred thousand years, represent a dramatic change in the Earth's environment. Although there is no satisfactory theory for such reversals, it is generally accepted that the dipole field intensity decreases to <20% of its 'normal' value for a few thousand years during the change in direction. Because the galactic and solar cosmic rays which impinge on the Earth's atmosphere are charged, a significant fraction (about half) of them are deflected by the geomagnetic field. At the time of a reversal, this magnetic shielding is greatly reduced, and it has been suggested that the increased flux of high-energy particles could have effects on evolutionary or climatic processes. For example, the statistically significant coincidence in levels of some marine faunal extinctions and reversal boundaries in ocean sediments could be caused, directly or indirectly, by the decreased geomagnetic intensity during the reversal. We report here evidence in marine sediments for an increase in cosmogenic 10Be production in the Earth's atmosphere during the Brunhes-Matuyama reversal 730,000 yr ago. In addition to confirming an increase in cosmogenic isotope production, the results provide information on the magnitude and duration of the geomagnetic intensity decrease during such an event, and the depth at which remanent magnetism is acquired in marine sediments