The cardiovascular risk profile of middle age women previously diagnosed with premature ovarian insufficiency: A case-control study

Background: Cardiovascular disease (CVD) is the leading cause of death in women worldwide. The cardiovascular risk profile deteriorates after women enter menopause. By definition, women diagnosed with premature ovarian insufficiency (POI) experience menopause before 40 years of age, which may render these women even more susceptible to develop CVD later in life. However, prospective long-term follow up data of well phenotyped women with POI are scarce. In the current study we compare the CVD profile and risk of middle aged women previously diagnosed with POI, to a population based reference group matched for age and BMI. Methods and findings: We compared 123 women (age 49.0 (± 4.3) years) and diagnosed with POI 8.1 (IQR: 6.8- 9.6) years earlier, with 123 population controls (age 49.4 (± 3.9) years). All women underwent an extensive standardized cardiovascular screening. We assessed CVD risk factors including waist circumference, BMI, blood pressure, lipid profile, pulse wave velocity (PWV), and the prevalence of diabetes mellitus, metabolic syndrome (MetS) and carotid intima media thickness (cIMT), in both women with POI and controls. We calculated the 10-year CVD Framingham Risk Score (FRS) and the American Heart Association's suggested cardiovascular health score (CHS). Waist circumference (90.0 (IQR: 83.0-98.0) versus 80.7 (IQR: 75.1-86.8), p < 0.01), waist-to-hip ratio (0.90 (IQR: 0.85-0.93) versus 0.79 (IQR: 0.75-0.83), p < 0.01), systolic blood pressure (124 (IQR 112-135) versus 120 (IQR109- 131), p < 0.04) and diastolic blood pressure (81 (IQR: 76-89) versus 78 (IQR: 71-86), p < 0.01), prevalence of hypertension (45 (37%) versus 21 (17%), p < 0.01) and MetS (19 (16%) versus 4 (3%), p < 0.01) were all significantly increased in women with POI compared to healthy controls. Other risk factors, however, such as lipids, glucose levels and prevalence of diabetes were similar comparing women with POI versus controls. The arterial stiffness assessed by PWV was also similar in both populations (8.1 (IQR: 7.1-9.4) versus 7.9 (IQR: 7.1-8.4), p = 0.21). In addition, cIMT was lower in women with POI compared to controls (550 ìm (500-615) versus 684 ìm (618-737), p < 0.01). The calculated 10-year CVD risk was 5.9% (IQR: 3.7-10.6) versus 6.0% (IQR: 3.9-9.0) (p = 0.31) and current CHS was 6.1 (1.9) versus 6.5 (1.6) (p = 0.07), respectively in POI versus controls. Conclusions: Middle age women with POI presented with more unfavorable cardiovascular risk factors (increased waist circumference and a higher prevalence of hypertension and MetS) compared to age and BMI matched population controls. In contrast, the current study reveals a lower cIMT and similar 10-year cardiovascular disease risk and cardiovascular health score. In summary, neither signs of premature atherosclerosis nor a worse cardiovascular disease risk or health score were observed among middle age women with POI compared to population controls. Longer-term follow-up studies of women of more advanced age are warranted to establish whether women with POI are truly at increased risk of developing CVD events later in life

Molecular subtypes of breast cancer and amplification of topoisomerase IIα: predictive role in dose intensive adjuvant chemotherapy

Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took part in a randomised study of adjuvant high-dose chemotherapy in breast cancer. In addition, the topoisomerase IIα (TOP2A) amplification status was determined by fluorescence in situ hybridisation and chromogenic in situ hybridisation. 411 of the 753 tumours (55%) were classified as luminal-like, 137 (18%) as basal-like and 205 (27%) as human epithelial receptor type 2 (HER2) amplified. The basal-like tumours were defined as having no expression of ER and HER2; 98 of them did express epidermal growth factor receptor and/or cytokeratin 5/6. The luminal-like tumours had a significantly better recurrence free and overall survival than the other two groups. From the 194 HER2-positive tumours, 47 (24%) were shown to harbour an amplification of TOP2A. Patients with an HER2-amplified tumour randomised to the high-dose therapy arm did worse than those in the conventional treatment arm, possibly caused by the lower cumulative anthracycline dose in the high-dose arm. The tumours with a TOP2A amplification contributed hardly to this difference, suggesting that TOP2A amplification is not the cause of the steep dose–response curve for anthracyclines in breast cancer. Possibly, the difference of the cumulative dose of only 25% between the treatment arms was insufficient to yield a survival difference

Effect of channel deepening on tidal flow and sediment transport—part II: muddy channels

Natural tidal channels often need deepening for navigation purposes (larger vessels). The depth increase may lead to tidal amplification, salt intrusion over longer distances, and increasing sand and mud import. Increasing fine sediment import, in turn, may start a process in which the sediment concentration progressively increases until the river becomes hyper-turbid, which may lead to increased dredging volumes and to decreased ecological values. These effects can be modeled and studied using detailed 3D models. Reliable simplified models for a first quick engineering evaluation are however lacking. In this paper, we apply both simplified and detailed 3D models to analyze the effects of channel deepening in prismatic and weakly converging tidal channels with saturated mud flow. The objective is to gain quantitative understanding of the effects of channel deepening on mud transport. We developed a simplified tidal mud model describing most relevant processes and effects in saturated mud flows with only minor horizontal transport gradients (quasi uniform conditions). The simplified model is not valid for non-saturated mud flow conditions. This model can either be used in standalone mode or in post-processing mode with computed near-bed velocities from a 3D hydrodynamic model as an input. The standalone model has been compared to various field data sets. Mud transport processes in the mouth region of muddy tidal channels can be realistically represented by the simplified model, if sufficient salinity and sediment data are available for calibration. The simulation of tidal mud transport and the behavior of an estuarine turbidity maximum (ETM) in saturated and non-saturated mud flow conditions cannot be represented by the simplified model and requires the application of a detailed 3D model

Effect of channel deepening on tidal flow and sediment transport—part II: muddy channels

Natural tidal channels often need deepening for navigation purposes (larger vessels). The depth increase may lead to tidal amplification, salt intrusion over longer distances, and increasing sand and mud import. Increasing fine sediment import, in turn, may start a process in which the sediment concentration progressively increases until the river becomes hyper-turbid, which may lead to increased dredging volumes and to decreased ecological values. These effects can be modeled and studied using detailed 3D models. Reliable simplified models for a first quick engineering evaluation are however lacking. In this paper, we apply both simplified and detailed 3D models to analyze the effects of channel deepening in prismatic and weakly converging tidal channels with saturated mud flow. The objective is to gain quantitative understanding of the effects of channel deepening on mud transport. We developed a simplified tidal mud model describing most relevant processes and effects in saturated mud flows with only minor horizontal transport gradients (quasi uniform conditions). The simplified model is not valid for non-saturated mud flow conditions. This model can either be used in standalone mode or in post-processing mode with computed near-bed velocities from a 3D hydrodynamic model as an input. The standalone model has been compared to various field data sets. Mud transport processes in the mouth region of muddy tidal channels can be realistically represented by the simplified model, if sufficient salinity and sediment data are available for calibration. The simulation of tidal mud transport and the behavior of an estuarine turbidity maximum (ETM) in saturated and non-saturated mud flow conditions cannot be represented by the simplified model and requires the application of a detailed 3D model

On the relation between predicted and observed aeolian transport rates: a field study at the Belgian coast

status: submitte

A Rational Method for the Design of Sand Dike/Dune Systems at Sheltered Sites; Wadden Sea Coast of Texel, The Netherlands

status: publishe

A Rational Method for the Design of Sand Dike/Dune Systems at Sheltered Sites; Wadden Sea Coast of Texel, The Netherlands

A rational method for the design of sand dike/dune systems at sheltered sites is presented, focussing on the cross-shore dimensions of the sand dike in relation to the local wave climate, tidal regime and available sandy materials. The example case is the new sand dike/dune system along the south-east coast of Texel, The Netherlands. The old dike protecting the island was not sufficiently strong to withstand an extreme storm event and has been strengthened by a new sand dune/dike. Various empirical and numerical models have been used, compared and validated to determine the erosion volumes during annual conditions and extreme storm events. Potential wind-induced (aeolian) sediment transport and erosion is also studied using the modified Bagnold-equation including the effects of grain size, moisture content and vegetation. The overall design method resulted into an innovative design solution, guarantying a naturally integrated and resilient sand protection as well as optimal coastal safety

Hydraulic approach for predicting piping in dikes

<p>This paper discusses a piping model that fundamentally differs from Sellmeijer’s model in relation to the structure of the formula used to calculate the critical hydraulic gradient at which backward erosion leads to dike failure. In this model, the laminar groundwater flow in the sand layer is schematized by characteristic discharges, which are estimated by Darcy’s Law. The laminar pipe flow and the incipient motion of the particles are described using equations of Hagen–Poiseuille, Darcy–Weisbach and Shields. The shear-stress concept of Grass is used to include the effects of the non-uniformity of the sand mixture on pipe erosion. Sellmeijer’s piping equations and the proposed piping model are compared using over 100 laboratory experiments and some field observations.</p