Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P(combined) = 4.09 × 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P(combined) = 2.74 × 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

The place(s) of student voice in 14-19 education policy reform: reflections on consultation and participation

Certain policy areas with considerable impact on young people's educational experiences and achievements, notably assessment and qualifications, do not involve consultation with young people to any meaningful extent. Findings from a national study, which included focus groups with 243 students in the 14-19 phase, are presented with respect to student consultation and participation in such policy areas. A lack of meaningful consultation regarding what students see as ‘higher level’ policy agendas was found (such as qualifications provision, choice or structure). Students are therefore ‘voiceless’ in relation to major qualifications reforms

Recombinant canine distemper virus strain Snyder Hill expressing green or red fluorescent proteins causes meningoencephalitis in the ferret

The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDV(SH)) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDV(SH) (rCDV(SH)) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV(5804P) and the prototypic wild-type CDV(R252) showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDV(SH)-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis.

Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain

Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.

Inorganic arsenic levels in rice milk exceed EU and US drinking water standards

Under EU legislation, total arsenic levels in drinking water should not exceed 10 microg l(-1), while in the US this figure is set at 10 microg l(-1) inorganic arsenic. All rice milk samples analysed in a supermarket survey (n = 19) would fail the EU limit with up to 3 times this concentration recorded, while out of the subset that had arsenic species determined (n = 15), 80% had inorganic arsenic levels above 10 microg l(-1), with the remaining 3 samples approaching this value. It is a point for discussion whether rice milk is seen as a water substitute or as a food, there are no EU or US food standards highlighting the disparity between water and food regulations in this respect.

Greatly enhanced arsenic shoot assimilation in rice leads to elevated grain levels compared to wheat and barley

Paired grain, shoot, and soil of 173 individual sample sets of commercially farmed temperate rice, wheat, and barley were surveyed to investigate variation in the assimilation and translocation of arsenic (As). Rice samples were obtained from the Carmargue (France), Doñana (Spain), Cadiz (Spain), California, and Arkansas. Wheat and barleywere collected from Cornwall and Devon (England) and the east coast of Scotland. Transfer of As from soil to grain was an order of magnitude greater in rice than for wheat and barley, despite lower rates of shoot-to-grain transfer. Rice grain As levels over 0.60 microg g(-1) d. wt were found in rice grown in paddy soil of around only 10 microg g(-1) As, showing that As in paddy soils is problematic with respect to grain As levels. This is due to the high shoot/soil ratio of approximately 0.8 for rice compared to 0.2 and 0.1 for barley and wheat, respectively. The differences in these transfer ratios are probably due to differences in As speciation and dynamics in anaerobic rice soils compared to aerobic soils for barley and wheat. In rice, the export of As from the shoot to the grain appears to be under tight physiological control as the grain/shoot ratio decreases by more than an order of magnitude (from approximately 0.3 to 0.003 mg/kg) and as As levels in the shoots increase from 1 to 20 mg/kg. A down regulation of shoot-to-grain export may occur in wheat and barley, but it was not detected at the shoot As levels found in this survey. Some agricultural soils in southwestern England had levels in excess of 200 microg g(-1) d. wt, although the grain levels for wheat and barley never breached 0.55 microg g(-1) d. wt. These grain levels were achieved in rice in soils with an order of magnitude lower As. Thus the risk posed by As in the human food-chain needs to be considered in the context of anaerobic verses aerobic ecosystems.

Market Basket Survey Shows Elevated Levels of As in South Central U.S. Processed Rice Compared to California: Consequences for Human Dietary Exposure:consequences for human dietary exposure

We report the largest market basket survey of arsenic (As) in U.S. rice to date. Our findings show differences in transitional-metal levels between polished and unpolished rice and geographical variation in As and selenium (Se) between rice processed in California and the South Central U.S. The mean and median As grain levels for the South Central U.S. were 0.30 and 0.27 µg As g-1, respectively, for 107 samples. Levels for California were 41% lower than the South Central U.S., with a mean of 0.17 µg As g-1 and a median of 0.16 µg As g-1 for 27 samples. The mean and median Se grain levels for the South Central U.S. were 0.19 µg Se g-1. Californian rice levels were lower, averaging only 0.08 and 0.06 µg Se g-1 for mean and median values, respectively. The difference between the two regions was found to be significant for As and Se (General Linear Model (GLM):? As p < 0.001; Se p < 0.001). No statistically significant differences were observed in As or Se levels between polished and unpolished rice (GLM:? As p = 0.213; Se p = 0.113). No significant differences in grain levels of manganese (Mn), cobalt (Co), copper (Cu), or zinc (Zn) were observed between California and the South Central U.S. Modeling arsenic intake for the U.S. population based on this survey shows that for certain groups (namely Hispanics, Asians, sufferers of Celiac disease, and infants) dietary exposure to inorganic As from elevated levels in rice potentially exceeds the maximum intake of As from drinking water (based on consumption of 1 L of 0.01 mg L-1 In. As) and Californian state exposure limits. Further studies on the transformation of As in soil, grain As bioavailability in the human gastrointestinal tract, and grain elemental speciation trends are critical.

Arsenic sequestration in iron plaque, its accumulation and speciation in mature rice plants (Oryza sativa L.)

A compartmented soil-glass bead culture system was used to investigate characteristics of iron plaque and arsenic accumulation and speciation in mature rice plants with different capacities of forming iron plaque on their roots. X-ray absorption near-edge structure spectra and extended X-ray absorption fine structure were utilized to identify the mineralogical characteristics of iron plaque and arsenic sequestration in plaque on the rice roots. Iron plaque was dominated by (oxyhydr)oxides, which were composed of ferrihydrite (81-100%), with a minor amount of goethite (19%) fitted in one of the samples. Sequential extraction and XANES data showed that arsenic in iron plaque was sequestered mainly with amorphous and crystalline iron (oxyhydr)oxides, and that arsenate was the predominant species. There was significant variation in iron plaque formation between genotypes, and the distribution of arsenic in different components of mature rice plants followed the following order: iron plaque > root > straw > husk > grain for all genotypes. Arsenic accumulation in grain differed significantly among genotypes. Inorganic arsenic and dimethylarsinic acid (DMA) were the main arsenic species in rice grain for six genotypes, and there were large genotypic differences in levels of DMA and inorganic arsenic in grain.

Degradation of 4-fluorobiphenyl by mycorrhizal fungi as determined by (19)F nuclear magnetic resonance spectroscopy and (14)C radiolabelling analysis

The pathways of biotransformation of 4-fluorobiphenyl (4FBP) by the ectomycorrhizal fungus Tylospora fibrilosa and several other mycorrhizal fungi were investigated by using (19)F nuclear magnetic resonance (NMR) spectroscopy in combination with (14)C radioisotope-detected high-performance liquid chromatography ((14)C-HPLC). Under the conditions used in this study T. fibrillosa and some other species degraded 4FBP. (14)C-HPLC profiles indicated that there were four major biotransformation products, whereas (19)F NMR showed that there were six major fluorine-containing products. We confirmed that 4-fluorobiphen-4'-ol and 4-fluorobiphen-3'-ol were two of the major products formed, but no other products were conclusively identified. There was no evidence for the expected biotransformation pathway (namely, meta cleavage of the less halogenated ring), as none of the expected products of this route were found. To the best of our knowledge, this is the first report describing intermediates formed during mycorrhizal degradation of halogenated biphenyls.

'Sliabh in Irish place-names' in Nomina 32 (2009)

This article deals with one of the most common elements in names of Irish hills and mountains. The grammar, phonology, etymology, semantic range and chronology of the element are examined. Sliabh is particularly complex in terms of its semantic range, which includes the following senses: 1) a mountain or hill (standing alone or forming part of a range); 2) a range of hills or mountains; 3) an moor or area of upland. The word is present in the earliest attested stages of the Irish language, and there is some evidence for all three meanings in Old Irish, though senses 1 and 2 are best attested. It is suggested that the view advanced by MacBain and Thurneysen that sliabh is etymologically related to Eng. slope and that this reflects its original meaning is open to some doubt in view of the lack of evidence for this sense in early Irish and the lack of clear cognates in other branches of Celtic and Indo-European languages.

Urinary deoxynivalenol is correlated with cereal intake in individuals from the United Kingdom

BACKGROUND: Deoxynivalenol (DON) is a toxic fungal metabolite that frequently contaminates cereal crops. DON is toxic to animals, but the effects on humans are poorly understood, in part because exposure estimates are of limited precision.

OBJECTIVES: In this study we used the U.K. adult National Diet and Nutrition Survey to compare 24-hr urinary DON excretion with cereal intake.

METHODS: One hundred subjects were identified for each of the following cereal consumption groups: low (mean, 107 g cereal/day; range, 88-125), medium (mean, 179 g/day; range, 162-195) and high (mean, 300 g/day, range, 276-325). DON was analyzed in 24-hr urine samples by liquid chromatography mass spectrometry after purification on immunoaffinity columns.

RESULTS: DON was detected in 296 of 300 (98.7%) urine samples. Cereal intake was significantly associated with urinary DON (P < 0.0005), with the geometric mean urinary levels being 6.55 mu g DON/day [95% confidence interval (CI), 5.71-7-531; 9.63 mu g/day (95% Cl, 8.39-11.05); and 13.24 mu g/day (95% Cl, 11.54-15.19) for low-, medium-, and high-intake groups, respectively. In multivariable analysis, wholemeal bread (p < 0.0005), white bread (p < 0.0005), "other" bread (p < 0.0005), buns/cakes (p = 0.003), high-fiber breakfast cereal (p = 0.016), and pasta (p = 0.017) were significantly associated with urinary DON. Wholemeal bread was associated with the greatest percent increase in urinary DON per unit of consumption, but white bread contributed approximately twice as much as wholemeal bread to the urinary DON levels because it was consumed in higher amounts.

CONCLUSION: The majority of adults in the United Kingdom appear to be exposed to DON, and on the basis of the urinary levels, we estimate that some individuals may exceed the European Union (EU) recommended maximum tolerable daily intake of 1,000 ng DON/kg (bw). This exposure biomarker will be a valuable toot for biomonitoring as part of surveillance strategies and in etiologic studies of DON and human disease risk.

Seven new loci associated with age-related macular degeneration

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P <5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P <5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

The prevalence of primary angle closure glaucoma in European derived populations: a systematic review

AIM: To estimate the prevalence of primary angle closure glaucoma (PACG) in European derived populations.

METHOD: Systematic review and modelling of PACG prevalence data from population studies. PACG was defined according to the ISGEO definition requiring structural and/or functional evidence of glaucomatous optic neuropathy. Prevalence estimates were applied to the 2010 United Nations projected population figures to estimate case numbers.

RESULTS: The prevalence of PACG in those 40 years or more is 0.4% (95% CI 0.3% to 0.5%). Age-specific prevalence values are 0.02% (CI 0.00 to 0.08) for those 40-49 years, 0.60% (0.27 to 1.00) for those 50-59 years, 0.20% (0.06 to 0.42) for those 60-69 years and 0.94% (0.63 to 1.35) for those 70 years and older. Three-quarters of all cases occur in female subjects (3.25 female to 1 male; CI 1.76 to 5.94).

CONCLUSION: This analysis provides a current evidence-based estimate of PACG prevalence in European derived populations and suggests there are 130,000 people in the UK, 1.60 million people in Europe and 581,000 people in the USA with PACG today. Accounting for ageing population structures, cases are predicted to increase by 19% in the UK, 9% in Europe and 18% in the USA within the next decade. PACG is more common than previously thought, and all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.