Haptoglobin Phenotype, Preeclampsia and Response to Supplementation with Vitamins C and E in Pregnant Women with Type 1 Diabetes.

Objective The phenotype of the antioxidant and pro-angiogenicprotein haptoglobin (Hp) predicts cardiovascular disease risk andtreatment response to antioxidant vitamins in individuals withdiabetes. Our objective was to determine whether Hp phenotypeinfluences pre-eclampsia risk, or the efficacy of vitamins C and Ein preventing pre-eclampsia, in women with type-1 diabetes.
Design This is a secondary analysis of a randomised controlledtrial in which women with diabetes received daily vitamins C andE, or placebo, from 8 to 22 weeks of gestation until delivery.
Setting Twenty-five antenatal metabolic clinics across the UK (innorth-west England, Scotland, and Northern Ireland).
Population Pregnant women with type-1 diabetes.
Methods Hp phenotype was determined in white women whocompleted the study and had plasma samples available (n = 685).
Main outcome measure Pre-eclampsia.
Results Compared with Hp 2-1, Hp 1-1 (OR 0.59, 95% CI 0.30–1.16) and Hp 2-2 (OR 0.93, 95% CI 0.60–1.45) were notassociated with significantly decreased pre-eclampsia risk afteradjusting for treatment group and HbA1c at randomisation. Ourstudy was not powered to detect an interaction between Hpphenotype and treatment response; however, our preliminaryanalysis sugge sts that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype (Hp 1-1, OR 0.77, 95%CI 0.22–2.71; Hp 2-1, OR 0.81, 95% CI 0.46–1.43; Hp 2-2, 0.67,95% CI 0.34–1.33), after adjusting for HbA1c at randomisation.
Conclusions The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes.

The role of angiogenic and antiangiogenic factors in the second trimester in the prediction of preeclampsia in pregnant women with type 1 diabetes

OBJECTIVE To assess the association between circulating angiogenic and antiangiogenic factors in the second trimester and risk of preeclampsia in women with type 1 diabetes.

RESEARCH DESIGN AND METHODS Maternal plasma concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) were available at 26 weeks of gestation in 540 women with type 1 diabetes enrolled in the Diabetes and Preeclampsia Intervention Trial.

RESULTS Preeclampsia developed in 17% of pregnancies (n = 94). At 26 weeks of gestation, women in whom preeclampsia developed later had significantly lower PlGF (median [interquartile range]: 231 pg/mL [120–423] vs. 365 pg/mL [237–582]; P < 0.001), higher sFlt-1 (1,522 pg/mL [1,108–3,393] vs. 1,193 pg/mL [844–1,630] P < 0.001), and higher sEng (6.2 ng/mL [4.9–7.9] vs. 5.1 ng/mL[(4.3–6.2]; P < 0.001) compared with women who did not have preeclampsia. In addition, the ratio of PlGF to sEng was significantly lower (40 [17–71] vs. 71 [44–114]; P < 0.001) and the ratio of sFlt-1 to PlGF was significantly higher (6.3 [3.4–15.7] vs. 3.1 [1.8–5.8]; P < 0.001) in women who later developed preeclampsia. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to a logistic model containing established risk factors (area under the curve [AUC], 0.813) significantly improved the predictive value (AUC, 0.850 and 0.846, respectively; P < 0.01) and significantly improved reclassification according to the integrated discrimination improvement index (IDI) (IDI scores 0.086 and 0.065, respectively; P < 0.001).

CONCLUSIONS These data suggest that angiogenic and antiangiogenic factors measured during the second trimester are predictive of preeclampsia in women with type 1 diabetes. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to established clinical risk factors significantly improves the prediction of preeclampsia in women with type 1 diabetes.

Preeclampsia is characterized by the development of hypertension and new-onset proteinuria during the second half of pregnancy (1,2), leading to increased maternal morbidity and mortality (3). Women with type 1 diabetes are at increased risk for development of preeclampsia during pregnancy, with rates being two-times to four-times higher than that of the background maternity population (4,5). Small advances have come from preventive measures, such as low-dose aspirin in women at high risk (6); however, delivery remains the only effective intervention, and preeclampsia is responsible for up to 15% of preterm births and a consequent increase in infant mortality and morbidity (7).

Although the etiology of preeclampsia remains unclear, abnormal placental vascular remodeling and placental ischemia, together with maternal endothelial dysfunction, hemodynamic changes, and renal pathology, contribute to its pathogenesis (8). In addition, over the past decade accumulating evidence has suggested that an imbalance between angiogenic factors, such as placental growth factor (PlGF), and antiangiogenic factors, such as soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng), plays a key role in the pathogenesis of preeclampsia (8,9). In women at low risk (10–13) and women at high risk (14,15), concentrations of angiogenic and antiangiogenic factors are significantly different between women who later develop preeclampsia (lower PlGF, higher sFlt-1, and higher sEng levels) compared with women who do not.

Few studies have specifically focused on circulating angiogenic factors and risk of preeclampsia in women with diabetes, and the results have been conflicting. In a small study, higher sFlt-1 and lower PlGF were reported at the time of delivery in women with diabetes who developed preeclampsia (16). In a longitudinal prospective cohort of pregnant women with diabetes, Yu et al. (17) reported increased sFlt-1 and reduced PlGF in the early third trimester as potential predictors of preeclampsia in women with type 1 diabetes, but they did not show any difference in sEng levels in women with preeclampsia compared with women without preeclampsia. By contrast, Powers et al. (18) reported only increased sEng in the second trimester in women with pregestational diabetes who developed preeclampsia.

The aim of this study, which was significantly larger than the previous studies highlighted, was to assess the association between circulating angiogenic (PlGF) and antiangiogenic (sFlt-1 and sEng) factors and the risk of preeclampsia in women with type 1 diabetes. A further aim was to evaluate the added predictive ability and clinical usefulness of angiogenic factors and established risk factors for preeclampsia risk prediction in women with type 1 diabetes.

Centennial-scale climate change in Ireland during the Holocene

We examine mid- to late Holocene centennial-scale climate variability in Ireland using proxy data from peatlands, lakes and a speleothem. A high degree of between-record variability is apparent in the proxy data and significant chronological uncertainties are present. However, tephra layers provide a robust tool for correlation and improve the chronological precision of the records. Although we can find no statistically significant coherence in the dataset as a whole, a selection of high-quality peatland water table reconstructions co-vary more than would be expected by chance alone. A locally weighted regression model with bootstrapping can be used to construct a ‘best-estimate’ palaeoclimatic reconstruction from these datasets. Visual comparison and cross-wavelet analysis of peatland water table compilations from Ireland and Northern Britain show that there are some periods of coherence between these records. Some terrestrial palaeoclimatic changes in Ireland appear to coincide with changes in the North Atlantic thermohaline circulation and solar activity. However, these relationships are inconsistent and may be obscured by chronological uncertainties. We conclude by suggesting an agenda for future Holocene climate research in Ireland. ©2013 Elsevier B.V. All rights reserved.

Interaction of combined chloride and sulfate ingression in concrete

Chloride is the most severe form of deterioration experienced by concrete and one of the principal sources of chlorides is sea water. However, the presence of sulfates in seawater will influence the movement of chloride ions and vice versa. This interaction is not well understood and current codes of practice provide no guidelines for such dual exposure.
An investigation to monitor combined effect of the ingress of chlorides and sulfates during a realistic 12 month wetting and drying exposure regime to simulate conditions in which multiple mode transport mechanisms are active was conducted on a variety of binders (PC, PFA and GGBS). Penetration was evaluated using water and acid soluble chloride profiles and sulfate profiles.
It was found that the nature of the exposure provided multiple modes of transport within the concrete, thus creating a complex pattern of distribution of ions. The presence of sulfates decreased the penetration of chlorides in the PC system at all ages relative to a chloride only control. The matrices containing PFA and GGBS also showed an initial decrease in chloride penetration. However, after six months the presence of sulfates then increased chloride penetration.

Discovery of WASP-65b and WASP-75b: Two hot Jupiters without highly inflated radii

We report the discovery of two transiting hot Jupiters, WASP-65b (M_pl = 1.55 ± 0.16 M_J; R_pl = 1.11 ± 0.06 R_J), and WASP-75b (M_pl = 1.07 ± 0.05 M_J; R_pl = 1.27 ± 0.05 R_J). They orbit their host star every ∼2.311, and ∼2.484 days, respectively. The planet host WASP-65 is a G6 star (T_eff = 5600 K, [Fe/H] = −0.07 ± 0.07, age 8 Gyr); WASP-75 is an F9 star (T_eff = 6100 K, [Fe/H] = 0.07 ± 0.09, age ∼ 3 Gyr). WASP-65b is one of the densest known exoplanets in the mass range 0.1 and 2.0 MJ (ρpl = 1.13 ± 0.08 ρJ), a mass range where a large fraction of planets are found to be inflated with respect to theoretical planet models. WASP-65b is one of only a handful of planets with masses of ∼1.5 MJ, a mass regime surprisingly underrepresented among the currently known hot Jupiters. The radius of WASP-75b is slightly inflated (10%) as compared to theoretical planet models with no core, and has a density similar to that of Saturn (ρpl = 0.52 ± 0.06 ρJ). Key words. planetary systems – stars: individual:

WASP-54b, WASP-56b and WASP-57b: Three new sub-Jupiter mass planets from SuperWASP

We present three newly discovered sub-Jupiter mass planets from the SuperWASP survey: WASP-54b is a heavily bloated planet of mass 0.636$^{+0.025}_{-0.024}$ \mj and radius 1.653$^{+0.090}_{-0.083}$ \rj. It orbits a F9 star, evolving off the main sequence, every 3.69 days. Our MCMC fit of the system yields a slightly eccentric orbit ($e=0.067^{+0.033}_{-0.025}$) for WASP-54b. We investigated further the veracity of our detection of the eccentric orbit for WASP-54b, and we find that it could be real. However, given the brightness of WASP-54 V=10.42 magnitudes, we encourage observations of a secondary eclipse to draw robust conclusions on both the orbital eccentricity and the thermal structure of the planet. WASP-56b and WASP-57b have masses of 0.571$^{+0.034}_{-0.035}$ \mj and $0.672^{+0.049}_{-0.046}$ \mj, respectively; and radii of $1.092^{+0.035}_{-0.033}$ \rj for WASP-56b and $0.916^{+0.017}_{-0.014}$ \rj for WASP-57b. They orbit main sequence stars of spectral type G6 every 4.67 and 2.84 days, respectively. WASP-56b and WASP-57b show no radius anomaly and a high density possibly implying a large core of heavy elements; possibly as high as $\sim$50 M$_{\oplus}$ in the case of WASP-57b. However, the composition of the deep interior of exoplanets remain still undetermined. Thus, more exoplanet discoveries such as the ones presented in this paper, are needed to understand and constrain giant planets' physical properties.

Development and validation of the first high performance-lateral flow immunoassay (HP-LFIA) for the rapid screening of domoic acid from shellfish extracts

A lateral flow immunoassay (LFIA) has been developed and fully validated to detect the primary amnesic shellfish poisoning (ASP) toxin, domoic acid (DA). The performance characteristics of two versions of the test were investigated using spiked and naturally contaminated shellfish (mussels, scallops, oysters, clams, and cockles). The tests provide a qualitative result, to indicate the absence or presence of DA in extracts of shellfish tissues, at concentrations that are relevant to regulatory limits. The new rapid assay (LFIA version 2) was designed to overcome the performance limitations identified in the first version of the assay. The improved test uses an electronic reader to remove the subjective nature of the generated results, and the positive cut-off for screening of DA in shellfish was increased from 10 ppm (version 1) to 17.5 ppm (version 2). A simple extraction and test procedure was employed, which required minimal equipment and materials; results were available 15 min after sample preparation. Stability of the aqueous extracts at room temperature (22 C) at four time points (up to 245 min after extraction) and across a range of DA concentrations was 100.3±1.3% and 98.8±2.4% for pre- and post-buffered extracts, respectively. The assay can be used both within laboratory settings and in remote locations. The accuracy of the new assay, to indicate negative results at or below 10 ppm DA, and positive results at or above 17.5 ppm, was 99.5% (n=216 tests). Validation data were obtained from a 2-day, randomised, blind study consisting of multiple LFIA lots (n=3), readers (n=3) and operators (n=3), carrying out multiple extractions of mussel tissue (n=3) at each concentration (0, 10, 17.5, and 20 ppm). No matrix effects were observed on the performance of the assay with different species (mussels, scallops, oysters, clams, and cockles). There was no impact on accuracy or interference from other phycotoxins, glutamic acid or glutamine with various strip incubations (8, 10, and 12 min). The accuracy of the assay, using naturally contaminated samples to indicate negative results at or below 12.5 ppm and positive results at or above 17.5 ppm, was 100%. Variability between three LFIA lots across a range of DA concentrations, expressed as coefficient of variation (% CV), was 1.1±0.4% (n=2 days) based on quantitative readings from the electronic reader. During an 8 week stability study, accuracy of the method with test strips stored at various temperatures (6, 22, 37 and 50 C) was 100%. Validation for both versions included comparisons with results obtained using reference LC-UV methods. © 2013 Elsevier B.V.