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.

LDL-containing immune complexes in the DCCT/EDIC cohort:associations with lipoprotein subclasses

Immune complexes containing modified LDL (LDL-IC) and NMR-determined Total LDL particle concentrations are significantly associated with intima-media thickness (IMT). We analyzed the associations between concentrations of NMR-determined lipoprotein subclasses and LDL-IC in the DCCT/EDIC cohort. LDL-IC concentrations in women and men of the DCCT/EDIC cohort did not differ significantly and were positively associated with Total LDL particle concentrations in men and women (r=0.34, r=0.32, respectively; P

Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications

Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort.

Increased methionine sulfoxide content of apoA-I in type 1 diabetes

Cardiovascular disease is a major cause of morbidity and premature mortality in diabetes. HDL plays an important role in limiting vascular damage by removing cholesterol and cholesteryl ester hydroperoxides from oxidized low density lipoprotein and foam cells. Methionine (Met) residues in apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, reduce peroxides in HDL lipids, forming methionine sulfoxide [Met(O)]. We examined the extent and sites of Met(O) formation in apoA-I of HDL isolated from plasma of healthy control and type 1 diabetic subjects to assess apoA-I exposure to lipid peroxides and the status of oxidative stress in the vascular compartment in diabetes. Three tryptic peptides of apoA-I contain Met residues: Q(84)-M(86)-K(88), W(108)-M(112)-R(116), and L(144)-M(148)-R(149). These peptides and their Met(O) analogs were identified and quantified by mass spectrometry. Relative to controls, Met(O) formation was significantly increased at all three locations (Met(86), Met(112), and Met(148)) in diabetic patients. The increase in Met(O) in the diabetic group did not correlate with other biomarkers of oxidative stress, such as N(epsilon)-malondialdehyde-lysine or N(epsilon)-(carboxymethyl)lysine, in plasma or lipoproteins. The higher Met(O) content in apoA-I from diabetic patients is consistent with increased levels of lipid peroxidation products in plasma in diabetes. Using the methods developed here, future studies can address the relationship between Met(O) in apoA-I and the risk, development, or progression of the vascular complications of diabetes.

Discharge kinetics of inductively coupled oxygen plasmas:Experiment and model

In this paper, neutral and charged particle dynamics in both the capacitive and inductive modes of an inductively coupled oxygen discharge are presented. Langmuir probes, laser-assisted photodetachment and two-photon laser-induced fluorescence are employed to measure plasma parameters in the 13.56MHz system for a range of plasma powers and gas pressures. It is found that the capacitive mode is more electronegative with lower molecular dissociation compared with the inductive mode. However, the negative ion density in each mode is comparable. A maximum is observed in the negative ion density and fraction with pressure for both modes. The experimental measurements are supplemented by a global model, which includes capacitive and inductive coupling effects. The model and experiments demonstrate that negative ion loss is dominated by ion-ion recombination and electron detachment at low pressures (

International Boundaries

International boundaries are a basic building block of the modern international state system. The international system dictates a clear spatial distinction between states. International boundaries are the agreed-upon delineation of the spatial allocation of one sovereign territory in relation to that of all others. From a formal perspective, the boundaries of a state delimit the area of applicability of a particular state's sovereignty and pose the only general limitation on the autonomy of sovereignties. Clear and defined boundaries are considered a precondition to the establishment of a state, and control over its boundaries is a sovereign prerogative, whereas an unauthorized breaching of state boundaries by other sovereign powers is considered a declaration of war.

The effect of the spectral distribution of wave energy on the performance of a bottom hinged flap type wave energy converter

The power output from a wave energy converter is typically predicted using experimental and/or numerical modelling techniques. In order to yield meaningful results the relevant characteristics of the device, together with those of the wave climate must be modelled with sufficient accuracy.

The wave climate is commonly described using a scatter table of sea states defined according to parameters related to wave height and period. These sea states are traditionally modelled with the spectral distribution of energy defined according to some empirical formulation. Since the response of most wave energy converters vary at different frequencies of excitation, their performance in a particular sea state may be expected to depend on the choice of spectral shape employed rather than simply the spectral parameters. Estimates of energy production may therefore be affected if the spectral distribution of wave energy at the deployment site is not well modelled. Furthermore, validation of the model may be affected by differences between the observed full scale spectral energy distribution and the spectrum used to model it.

This paper investigates the sensitivity of the performance of a bottom hinged flap type wave energy converter to the spectral energy distribution of the incident waves. This is investigated experimentally using a 1:20 scale model of Aquamarine Power’s Oyster wave energy converter, a bottom hinged flap type device situated at the European Marine Energy Centre (EMEC) in approximately 13m water depth. The performance of the model is tested in sea states defined according to the same wave height and period parameters but adhering to different spectral energy distributions.

The results of these tests show that power capture is reduced with increasing spectral bandwidth. This result is explored with consideration of the spectral response of the device in irregular wave conditions. The implications of this result are discussed in the context of validation of the model against particular prototype data sets and estimation of annual energy production.

In pursuit of regulatory compliance: a study of planning enforcement structures in Northern Ireland

As devolution expands across the UK, Northern Ireland (NI) is witnessing the development of new architecture to devolve planning powers. With serious criticism targeted at the legislative provisions for enforcement, this investigation endeavours to assess the robustness of the planning framework through a synergy of theory, law and practice. The paper demonstrates the value of theory in not only supplying a lens that allows both legislative frameworks and praxis to be deconstructed, but also in enabling the identification and scrutiny of underlying problems that pervade the system.

Political Liberalism, Free Speech and Public Reason

In this paper, I critically assess John Rawls' repeated claim that the duty of civility is only a moral duty and should not be enforced by law. In the first part of the paper, I examine and reject the view that Rawls' position may be due to the practical difficulties that the legal enforcement of the duty of civility might entail. I thus claim that Rawls' position must be driven by deeper normative reasons grounded in a conception of free speech. In the second part of the paper, I therefore examine various arguments for free speech and critically assess whether they are consistent with Rawls' political liberalism. I first focus on the arguments from truth and self-fulfilment. Both arguments, I argue, rely on comprehensive doctrines and therefore cannot provide a freestanding political justification for free speech. Freedom of speech, I claim, can be justified instead on the basis of Rawls' political conception of the person and of the two moral powers. However, Rawls' wide view of public reason already allows scope for the kind of free speech necessary for the exercise of the two moral powers and therefore cannot explain Rawls' opposition to the legal enforcement of the duty of civility. Such opposition, I claim, can only be explained on the basis of a defence of unconstrained freedom of speech grounded in the ideas of democracy and political legitimacy. Yet, I conclude, while public reason and the duty of civility are essential to political liberalism, unconstrained freedom of speech is not. Rawls and political liberals could therefore renounce unconstrained freedom of speech, and endorse the legal enforcement of the duty of civility, while remaining faithful to political liberalism.

Practice and Policy in the UK with Children and Young People who Display Harmful Sexual Behaviour: An analysis and critical review

This article considers the trajectory and effectiveness of policy, procedures and practice in the UK since the early 1990s in responding to young people who display problematic and harmful sexual behaviours. It draws on data from three publications in which research, policy and practice in the last 20 years have been reviewed. Key themes raised by Masson and Hackett are revisited including: denial and minimisation; terminology and categorisation; similarities with other young offenders; the child protection and youth justice systems; and assessment and interventions. The authors find that there is improvement in recognition of, and practice in response to, this group of young people, but good practice standards are inconsistently applied. With devolution of political powers, Scotland and Northern Ireland are now embarking on a more strategic response than England. The absence of a public debate and prioritising of primary prevention of child sexual abuse is noted.

The executive committee of the Greek Professional Association of Social Work in an age of austerity: examining its response

This paper explores the response by the Greek Association of Social Workers (SKLE) to Greece's current economic crisis. Socioeconomic conditions in Greece have deteriorated rapidly since the imposition of a Structural Adjustment Programme as a condition of the loan Troika provided to Greece to address its class-based public debt crisis. Interviews were conducted with SKLE Executive Committee members to examine SKLE's response in the context of newly raised inequalities. Research results show that SKLE recognised the negative consequences to both service users and its members. However, SKLE continues to reformulate its strategy mostly as a social partner. SKLE's previous strategy entailed amongst other things the analysis of policy proposals and participation in welfare related government committees. This strategy is no longer relevant because decision-making powers have been transferred to transnational bodies. This paper elaborates on these findings and discusses the barriers that prohibit SKLE from differentiation of its strategy. Although the research is country specific, it has implications for the broader global debate because professional associations must reformulate their strategies for better serving of both their constituents and the collective good based on the social justice mandate of the profession.

Online Thévenin Equivalent Determination Considering System Side Changes and Measurement Errors

This paper presents a new method for online determination of the Thèvenin equivalent parameters of a power system at a given node using the local PMU measurements at that node. The method takes into account the measurement errors and the changes in the system side. An analysis of the effects of changes in system side is carried out on a simple two-bus system to gain an insight of the effect of system side changes on the estimated Thévenin equivalent parameters. The proposed method uses voltage and current magnitudes as well as active and reactive powers; thus avoiding the effect of phase angle drift of the PMU and the need to synchronize measurements at different instances to the same reference. Applying the method to the IEEE 30-bus test system has shown its ability to correctly determine the Thévenin equivalent even in the presence of measurement errors and/or system side changes.

On convergence with hiccups: recent amendments to Poland's competition law

Discusses the amendments to the Polish Competition Act 2007 adopted in June 2014 which aim to enhance the effectiveness of antitrust enforcement, including the introduction of: (1) civil fines for individuals; (2) a "leniency plus" programme based on the US model; (3) a settlement procedure; and (4) extended inspection powers for the Competition Authority. Assesses the likely effectiveness of the reforms.

Varieties of resource nationalism in sub-Saharan Africa’s energy and minerals markets

This article examines resource nationalism in sub-Saharan Africa's energy and minerals markets. It does so by exploring economic and political developments in three cases: Nigeria as an example of a petro-state established by means of expropriation in the wake of decolonisation; South Africa, a mature mining industry shaped by its settler colonial history; and Mozambique, a new and therefore highly-dependent entrant into the league of significant natural gas producers. Extractive industries have played a controversial role in sub-Saharan Africa due in particular to the prevalence of the resource curse. Nevertheless, energy exports will continue to play an important role in fuelling economic growth and, potentially, also development as new deposits of natural gas and oil are discovered across the region. Resource nationalism has, moreover, increasingly constrained operations of the traditionally dominant Western energy companies, in particular as competition from state-owned energy companies in sub-Saharan Africa and from emerging powers such as China is increasing.

Cognitive amplify-and-forward relay networks with beamforming under primary user power constraint over Nakagami-m fading channels

In this paper, we analyze the performance of cognitive amplify-and-forward (AF) relay networks with beamforming under the peak interference power constraint of the primary user (PU). We focus on the scenario that beamforming is applied at the multi-antenna secondary transmitter and receiver. Also, the secondary relay network operates in channel state information-assisted AF mode, and the signals undergo independent Nakagami-m fading. In particular, closed-form expressions for the outage probability and symbol error rate (SER) of the considered network over Nakagami-m fading are presented. More importantly, asymptotic closed-form expressions for the outage probability and SER are derived. These tractable closed-form expressions for the network performance readily enable us to evaluate and examine the impact of network parameters on the system performance. Specifically, the impact of the number of antennas, the fading severity parameters, the channel mean powers, and the peak interference power is addressed. The asymptotic analysis manifests that the peak interference power constraint imposed on the secondary relay network has no effect on the diversity gain. However, the coding gain is affected by the fading parameters of the links from the primary receiver to the secondary relay network