Proceedings of the Rank Forum on Vitamin D

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations . 75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

Acute ingestion of a meal rich in n-3 polyunsaturated fatty acids results in rapid gastric emptying in humans

Background: n-3 Polyunsaturated fatty acids (PUFAs) have proven benefits for both the development of atherosclerosis and inflammatory conditions. The effects on atherosclerosis may be partly mediated by the observed reduction in fasting and postprandial triacylglycerol concentrations after both acute and chronic n-3 PUFA ingestion. Objective: The aim of this study was to assess gastric emptying and gastrointestinal hormone release after the consumption of mixed meals rich in n-3 PUFAs or other classes of fatty acids. Design: Ten healthy women (aged 50–62 y) completed 4 separate study visits in a single-blind, randomized design. On each occasion, subjects consumed 40 g oil rich in either saturated fatty acids, monounsaturated fatty acids, n-6 PUFAs, or n-3 PUFAs as part of a mixed meal. [1-13C]Octanoic acid (100 mg) was added to each oil. Gastric emptying was assessed by a labeled octanoic acid breath test, and concentrations of gastrointestinal hormones and plasma lipids were measured. Results: Recovery of 13C in breath was enhanced after n-3 PUFA ingestion (P < 0.005). The cholecystokinin response after the n-3 PUFA meal was significantly delayed (P < 0.001), and the glucagon-like peptide 1 response was significantly reduced (P < 0.05). Conclusion: The inclusion of n-3 PUFAs in a meal alters the gastric emptying rate, potentially as the result of changes in the pattern of cholecystokinin and glucagon-like peptide 1 release.

Observations of ice multiplication in a weakly convective cell embedded in supercooled mid-level stratus

Simultaneous observations of cloud microphysical properties were obtained by in-situ aircraft measurements and ground based Radar/Lidar. Widespread mid-level stratus cloud was present below a temperature inversion (~5 °C magnitude) at 3.6 km altitude. Localised convection (peak updraft 1.5 m s−1) was observed 20 km west of the Radar station. This was associated with convergence at 2.5 km altitude. The convection was unable to penetrate the inversion capping the mid-level stratus. The mid-level stratus cloud was vertically thin (~400 m), horizontally extensive (covering 100 s of km) and persisted for more than 24 h. The cloud consisted of supercooled water droplets and small concentrations of large (~1 mm) stellar/plate like ice which slowly precipitated out. This ice was nucleated at temperatures greater than −12.2 °C and less than −10.0 °C, (cloud top and cloud base temperatures, respectively). No ice seeding from above the cloud layer was observed. This ice was formed by primary nucleation, either through the entrainment of efficient ice nuclei from above/below cloud, or by the slow stochastic activation of immersion freezing ice nuclei contained within the supercooled drops. Above cloud top significant concentrations of sub-micron aerosol were observed and consisted of a mixture of sulphate and carbonaceous material, a potential source of ice nuclei. Particle number concentrations (in the size range 0.1

A policy critique of Stansted Airport's expansion to 25 million passengers per annum (MPPA)

In this paper we undertake a preliminary assessment of the regional planning and development implications of BAA Stansted Airport’s planning permission to grow to 25 million passengers per annum (mppa) by 2010. Our concern is not simply to consider the overall growth of the airport on the airport site itself but the nature and type of growth both on- and off-site. In this document we focus on the submitted planning permission documents and test them. The methodology we employed was to draw on published and unpublished numerical estimates of the airport’s growth – particularly including estimates produced by the airport owner, BAA, and their economic and planning consultants DTZ Pieda - and critically, and systematically analyse their figures. We adopted this approach because unless the figures which were employed in the initial calculations were correct then all of the subsequent projections which flow from them - and the polices which could then be based on them – could be flawed. The analysis is divided into two parts – firstly, are the growth forecasts correct?; and secondly, what do these forecasts actually mean in developmental terms? In effect, what we have done is to produce a critique of the existing body of evidence by questioning underpinning assumptions and then draw some preliminary conclusions for the region based on this analysis. A major focus of this report has been analyse the figures involved in the planning application to expand Stansted to 25mppa. Ironically, one of our key findings, that the local impact of Stansted’s proposed expansion in employment terms might well be less than was originally thought, might make it easier to gain the acceptance of the relevant local authorities involved to allow the development to take place. Our main overall findings are that the BAA projections over-estimate the local employment impact of the airport’s proposed growth and under-estimate its potential regional ‘transportation’ employment effect. These two findings are, of course, related to each other in important ways, and we also feel that they have potentially significant medium and long-term economic, competitiveness and planning policy implications for the East of England region

The anions [(ZrOH(CO3)3)2]6− and [(ZrOH(C2O4)3)2]6−: single crystal X-ray diffraction studies of the complexes guanidinium zirconium carbonate [(C(NH2)3)3ZrOH(CO3)3·H2O]2 and sodium zirconium oxalate Na6(ZrOH(C2O4)3)2·7H2O

The complex [(C(NH2)3)3ZrOH(CO3)3·H2O]2 (A) has been shown by means of a single crystal X-ray diffraction study to contain [C(NH2)3]+ cations and dimeric anions of formulation [(ZrOH(CO3)3)2]6−. The anion is centrosymmetric with each metal being bonded to two bridging OH groups and three chelating CO2−3 ions. The Zr atoms are thus eight coordinate with a dodecahedral environments. The ZrO distances formed by the bridgng OH groups are shorter than those formed through zirconiu carbonate interactions. The non-bonded Zr…Zr distance is 3.47(2) Å. An infrared spectroscopic investigation of A provides data which support the findings of the crystallographic study. Likewise the complex Na6(ZrOH(CO2O4)3)2·7H2O (B) contains the anion [(ZrOH(C2O4)3)2]6−. This anion is structurally related to the anion in A as each Zr atom has an eight-coordinate dodecahedral environment being bonded to two bridging OH groups and three chelating oxalate ligands, but has no imposed crysallographic symmetry. The Zr…Zr non-bonded distance is 3.50(1) Å. The OZrO bridge angles are 69.7(4)° and A and 67.4(3)° in B.

Structure of the DNA octanucleotide d(ACGTACGT)2

d(ACGTACGT), C78H84N30O32P7.20H2O, Mr (DNA) = 2170, tetragonal, P43212 (No 96), a = 42.845 (1), b = 42.845(1), c = 24.804 (1) Å, V = 45532.5 (2) Å3, z = 8,(MoK) = 0.71069 Å,µ(MoK) = 0.10 mm-1, T = 295 K, R = 0.18 for 1994 unique reflections between 5.0 and 1.9 Å resolution. The self-complementary octanucleotide d(ACGTACGT)2 has been crystallized and its structure determined to a resolution of 1.9 Å. The asymmetric unit consists of a single strand of octamer with 20 water molecules. It is only the second example of an octanucleotide having terminal A·T base pairs whose structure has been determined by X-ray crystallography. The sequence adopts the modified A-type conformation found for all octanucleotide duplexes studied to date with the helix bent by approximately 15° and an average tilt angle of 0°. Unusually the data collection was carried out using a 3 kW molybdenum sealed-tube source. The conformational details are discussed in comparison with other closely related sequences.

Modulation of endothelial cell KCa3.1 Channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries

Arterial hyperpolarization to acetylcholine (ACh) reflects coactivation of KCa3.1 (IKCa) channels and KCa2.3 (SKCa) channels in the endothelium that transfers through myoendothelial gap junctions and diffusible factor(s) to affect smooth muscle relaxation (endothelium-derived hyperpolarizing factor [EDHF] response). However, ACh can differentially activate KCa3.1 and KCa2.3 channels, and we investigated the mechanisms responsible in rat mesenteric arteries. KCa3.1 channel input to EDHF hyperpolarization was enhanced by reducing external [Ca2+]o but blocked either with forskolin to activate protein kinase A or by limiting smooth muscle [Ca2+]i increases stimulated by phenylephrine depolarization. Imaging [Ca2+]i within the endothelial cell projections forming myoendothelial gap junctions revealed increases in cytoplasmic [Ca2+]i during endothelial stimulation with ACh that were unaffected by simultaneous increases in muscle [Ca2+]i evoked by phenylephrine. If gap junctions were uncoupled, KCa3.1 channels became the predominant input to EDHF hyperpolarization, and relaxation was inhibited with ouabain, implicating a crucial link through Na+/K+-ATPase. There was no evidence for an equivalent link through KCa2.3 channels nor between these channels and the putative EDHF pathway involving natriuretic peptide receptor-C. Reconstruction of confocal z-stack images from pressurized arteries revealed KCa2.3 immunostain at endothelial cell borders, including endothelial cell projections, whereas KCa3.1 channels and Na+/K+-ATPase {alpha}2/{alpha}3 subunits were highly concentrated in endothelial cell projections and adjacent to myoendothelial gap junctions. Thus, extracellular [Ca2+]o appears to modify KCa3.1 channel activity through a protein kinase A-dependent mechanism independent of changes in endothelial [Ca2+]i. The resulting hyperpolarization links to arterial relaxation largely through Na+/K+-ATPase, possibly reflecting K+ acting as an EDHF. In contrast, KCa2.3 hyperpolarization appears mainly to affect relaxation through myoendothelial gap junctions. Overall, these data suggest that K+ and myoendothelial coupling evoke EDHF-mediated relaxation through distinct, definable pathways.

Transition of pupils from Key Stage 2 to 3 deemed gifted and talented in mathematics: an initial study

In this article Geoff Tennant and Dave Harries report on the early stages of a research project looking to examine the transition from Key Stage (KS) 2 to 3 of children deemed Gifted and Talented (G&T) in mathematics. An examination of relevant literature points towards variation in definition of key terms and underlying rationale for activities. Preliminary fieldwork points towards a lack of meaningful communication between schools, with primary school teachers in particular left to themselves to decide how to work with children deemed G&T. Some pointers for action are given, along with ideas for future research and a request for colleagues interested in working with us to get in touch.

The North Atlantic jet stream under climate change and its relation to the NAO and EA patterns

This paper describes recent variations of the North Atlantic eddy-driven jet stream and analyzes the mean response of the jet to anthropogenic forcing in climate models. Jet stream changes are analyzed both using a direct measure of the near-surface westerly wind maximum and using an EOF-based approach. This allows jet stream changes to be related to the widely used leading patterns of variability: the North Atlantic Oscillation (NAO) and East Atlantic (EA) pattern. Viewed in NAO–EA state space, isolines of jet latitude and speed resemble a distorted polar coordinate system, highlighting the dependence of the jet stream quantities on both spatial patterns. Some differences in the results of the two methods are discussed, but both approaches agree on the general characteristics of the climate models. While there is some agreement between models on a poleward shift of the jet stream in response to anthropogenic forcing, there is still considerable spread between different model projections, especially in winter. Furthermore, the model responses to forcing are often weaker than their biases when compared to a reanalysis. Diagnoses of jet stream changes can be sensitive to the methodologies used, and several aspects of this are also discussed.

The role of atmosphere feedbacks during ENSO in the CMIP3 models. Part III: the shortwave flux feedback

Previous studies using coupled general circulation models (GCMs) suggest that the atmosphere model plays a dominant role in the modeled El Nin ̃ o–Southern Oscillation (ENSO), and that intermodel differences in the thermodynamical damping of sea surface temperatures (SSTs) are a dominant contributor to the ENSO amplitude diversity. This study presents a detailed analysis of the shortwave flux feedback (aSW) in 12 Coupled Model Intercomparison Project phase 3 (CMIP3) simulations, motivated by findings that aSW is the primary contributor to model thermodynamical damping errors. A ‘‘feedback decomposition method,’’ developed to elucidate the aSW biases, shows that all models un- derestimate the dynamical atmospheric response to SSTs in the eastern equatorial Pacific, leading to un- derestimated aSW values. Biases in the cloud response to dynamics and the shortwave interception by clouds also contribute to errors in aSW. Changes in the aSW feedback between the coupled and corresponding atmosphere-only simulations are related to changes in the mean dynamics. A large nonlinearity is found in the observed and modeled SW flux feedback, hidden when linearly cal- culating aSW. In the observations, two physical mechanisms are proposed to explain this nonlinearity: 1) a weaker subsidence response to cold SST anomalies than the ascent response to warm SST anomalies and 2) a nonlinear high-level cloud cover response to SST. The shortwave flux feedback nonlinearity tends to be underestimated by the models, linked to an underestimated nonlinearity in the dynamical response to SST. The process-based methodology presented in this study may help to correct model ENSO atmospheric biases, ultimately leading to an improved simulation of ENSO in GCMs.

Syntheses, characterization and X-ray crystal structures of a mono- and a penta-nuclear nickel(II) complex with oximato Schiff base ligands

A mononuclear octahedral nickel(II) complex [Ni(HL(1))(2)](SCN)(2) (1) and an unusual penta-nuclear complex [{(NiL(2))(mu-SCN)}(4)Ni(NCS)(2)]center dot 2CH(3)CN (2) where HL(1) = 3-(2-aminoethylimino)butan-2-one oxime and HL(2) = 3-(hydroxyimino)butan-2-ylidene)amino)propylimino)butan-2-one oxime have been prepared and characterized by X-ray crystallography. The mono-condensed ligand, HL(1), was prepared by the 1:1 condensation of the 1,2-diaminoethane with diacetylmonoxime in methanol under high dilution. Complex 1 is found to be a mer isomer and the amine hydrogen atoms are involved in extensive hydrogen bonding with the thiocyanate anions. The dicondensed ligand, HL(2), was prepared by the 1:2 condensation of the 1,3-diaminopropane with diacetylmonoxime in methanol. The central nickel(II) in 2 is coordinated by six nitrogen atoms of six thiocyanate groups, four of which utilize their sulphur atoms to connect four NiL2 moieties to form a penta-nuclear complex and it is unique in the sense that this is the first thiocyanato bridged penta-nuclear nickel(II) compound with Schiff base ligands.

Lanthanide speciation in potential SANEX and GANEX actinide/ 2 lanthanide separations using Tetra-N-Donor extractants

Lanthanide(III) complexes with N-donor ex-tractants, which exhibit the potential for the separation of minor actinides from lanthanides in the management of spent nuclear fuel, have been directly synthesized and characterized in both solution and solid states. Crystal structures of the Pr3+, Eu3+, Tb3+, and Yb3+ complexes of 6,6′-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin3-yl)-1,10-phenanthroline(CyMe4-BTPhen) and the Pr3+, Eu3+, and Tb3+ complexes of 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotria-zin-3-yl)-2,2′-bypyridine (CyMe4-BTBP) were obtained. The majority of these structures displayed coordination of two ofthe tetra-N-donor ligands to each Ln3+ ion, even when in some cases the complexations were performed with equimolar amounts of lanthanide and N-donor ligand. The structures showed that generally the lighter lanthanides had their coordination spheres completed by a bidentate nitrate ion, giving a 2+ charged complex cation, whereas the structures of the heavier lanthanides displayed tricationic complex species with a single water molecule completing their coordination environments. Electronic absorption spectroscopic titrations showed formation of the 1:2 Ln3+/LN4‑donor species (Ln = Pr3+, Eu3+, Tb3+) in methanol when the N-donor ligand was in excess. When the Ln3+ ion was in excess, evidence for formation of a 1:1 Ln3+/LN4‑donor complex species was observed. Luminescent lifetime studies of mixtures of Eu3+ with excess CyMe4-BTBP and CyMe4-BTPhen in methanol indicated that the nitrate-coordinated species is dominant in solution. X-ray absorption spectra of Eu3+ and Tb3+ species, formed by extraction from an acidic aqueous phase into an organic solution consisting of excess N-donor extractant in pure cyclohexanone or 30% tri-n-butyl phosphate (TBP) in cyclohexanone, were obtained. The presence of TBP in the organic phase did not alter lanthanide speciation. Extended X-ray absorption fine structure data from these spectra were fitted using chemical models established by crystallography and solution spectroscopy and showed the dominant lanthanide species in the bulk organic phase was a 1:2 Ln3+/LN‑donor species.

The stability of a two-dimensional vorticity filament under uniform strain

The quantitative effects of uniform strain and background rotation on the stability of a strip of constant vorticity (a simple shear layer) are examined. The thickness of the strip decreases in time under the strain, so it is necessary to formulate the linear stability analysis for a time-dependent basic flow. The results show that even a strain rate γ (scaled with the vorticity of the strip) as small as 0.25 suppresses the conventional Rayleigh shear instability mechanism, in the sense that the r.m.s. wave steepness cannot amplify by more than a certain factor, and must eventually decay. For γ < 0.25 the amplification factor increases as γ decreases; however, it is only 3 when γ e 0.065. Numerical simulations confirm the predictions of linear theory at small steepness and predict a threshold value necessary for the formation of coherent vortices. The results help to explain the impression from numerous simulations of two-dimensional turbulence reported in the literature that filaments of vorticity infrequently roll up into vortices. The stabilization effect may be expected to extend to two- and three-dimensional quasi-geostrophic flows.

Overall and income specific effect on prevalence of overweight and obesity of 20% sugar sweetened drink tax in UK: econometric and comparative risk assessment modelling study

Objective To model the overall and income specific effect of a 20% tax on sugar sweetened drinks on the prevalence of overweight and obesity in the UK. Design Econometric and comparative risk assessment modelling study. Setting United Kingdom. Population Adults aged 16 and over. Intervention A 20% tax on sugar sweetened drinks. Main outcome measures The primary outcomes were the overall and income specific changes in the number and percentage of overweight (body mass index ≥25) and obese (≥30) adults in the UK following the implementation of the tax. Secondary outcomes were the effect by age group (16-29, 30-49, and ≥50 years) and by UK constituent country. The revenue generated from the tax and the income specific changes in weekly expenditure on drinks were also estimated. Results A 20% tax on sugar sweetened drinks was estimated to reduce the number of obese adults in the UK by 1.3% (95% credible interval 0.8% to 1.7%) or 180 000 (110 000 to 247 000) people and the number who are overweight by 0.9% (0.6% to 1.1%) or 285 000 (201 000 to 364 000) people. The predicted reductions in prevalence of obesity for income thirds 1 (lowest income), 2, and 3 (highest income) were 1.3% (0.3% to 2.0%), 0.9% (0.1% to 1.6%), and 2.1% (1.3% to 2.9%). The effect on obesity declined with age. Predicted annual revenue was £276m (£272m to £279m), with estimated increases in total expenditure on drinks for income thirds 1, 2, and 3 of 2.1% (1.4% to 3.0%), 1.7% (1.2% to 2.2%), and 0.8% (0.4% to 1.2%). Conclusions A 20% tax on sugar sweetened drinks would lead to a reduction in the prevalence of obesity in the UK of 1.3% (around 180 000 people). The greatest effects may occur in young people, with no significant differences between income groups. Both effects warrant further exploration. Taxation of sugar sweetened drinks is a promising population measure to target population obesity, particularly among younger adults.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.