Being at the right place at the right time.

I am tremendously honored to receive the 2012 Women in Cell Biology Junior Award. In this essay, I recount my career path over the past 15 years. Although many details are specific to my own experiences, I hope that some generalizations can be made to encourage more women to pursue independent scientific careers. Mine is a story of choosing a captivating question, making the most of your opportunities, and finding a balance with life outside the lab.

Portal Vein Embolization before Right Hepatectomy: Improved Results Using n-Butyl-Cyanoacrylate Compared to Microparticles Plus Coils.

BACKGROUND: There is currently no consensus in the literature on which embolic agent induces the greatest degree of liver hypertrophy after portal vein embolization (PVE). Only experimental results in a pig model have demonstrated an advantage of n-butyl-cyanoacrylate (NBCA) over 3 other embolic materials (hydrophilic gel, small and large polyvinyl alcohol particles) for PVE. Therefore, the aim of this human study was to retrospectively compare the results of PVE using NBCA with those using spherical microparticles plus coils. METHODS: A total of 34 patients underwent PVE using either NBCA (n = 20), or spherical microparticles plus coils (n = 14). PVE was decided according to preoperative volumetry on the basis of contrast-enhanced CT. Groups were compared for age, sex, volume of the left lobe before PVE and future remnant liver ratio (FRL) (volume of the left lobe/total liver volume - tumor volume). The primary end point was the increase in left lobe volume 1 month after PVE. Secondary end points were procedure complications and biological tolerance. RESULTS: Both groups were similar in terms of age, sex ratio, left lobe volume, and FRL before PVE. NBCA induced a greater increase in volume after PVE than did microparticles plus coils (respectively, +74 ± 69 % and +23 ± 14 %, p < 0.05). The amount of contrast medium used for the procedure was significantly larger when microparticles and coils rather than NBCA were used (respectively, 264 ± 43 ml and 162 ± 34 ml, p < 0.01). The rate of PVE complications as well as the biological tolerance was similar in both groups. CONCLUSION: NBCA seems more effective than spherical microparticles plus coils to induce left-lobe hypertrophy.

Diagnosis of right ventricular dysfunction in acute pulmonary embolism using helical computed tomography.

Forty-six consecutive patients with pulmonary embolism (PE) who underwent pulmonary angiography, helical computed tomography (CT), and echocardiography in the investigators' emergency department were studied. It was determined that the CT right ventricular (RV)/left ventricular (LV) end-diastolic area ratio was correlated with PE obstruction and echocardiography. A CT RV/LV area ratio &gt;1 had a sensitivity of 88% and a specificity of 88% in diagnosing significant PE. The present study suggests that helical CT may be used as a triage tool in acute PE for selecting high-risk patients, using calculation of the RV/LV area ratio to detect RV dysfunction.

The class basis of the cleavage between the New Left and the radical right: An analysis for Austria, Denmark, Norway and Switzerland

This chapter argues that the electoral competition between the New Left and the Radical Right is best understood as a cultural divide anchored in different class constituencies. Based on individual-level data from the European Social Survey, we analyze the links between voters' class position, their economic and cultural preferences and their party choice for four small and affluent European countries. We find a striking similarity in the class pattern across countries. Everywhere, the New Left attracts disproportionate support from socio-cultural professionals and presents a clear-cut middle-class profile, whereas the Radical Right is most successful among production and service workers and receives least support from professionals. In general, the Radical Right depends on the votes of lowereducated men and older citizens and has turned into a new type of working-class party. However, its success within the working-class is not due to economic, but to cultural issues. The voters of the Radical Right collide with those of the New Left over a cultural conflict of identity and community - and not over questions of redistribution. A full-grown cleavage has thus emerged in the four countries under study, separating a libertarian-universalistic pole from an authoritarian-communitarian pole and going along with a process of class realignment.

Dispatch centres: what is the right population catchment size?

Literature on medical dispatch is growing, focusing mainly on efficiency (under and overtriage) and dispatch-assisted CPR. But the issue of population catchment size, functional costs and rationalization is rarely addressed. If we can observe a trend toward a decreasing number of dispatch centres in many European countries, there is today no evidence on what is the right catchment size to reach the best balance between quality of services and costs.

Different degrees of ischaemic injury in the right and left ventricle in cases of severe, nonfatal, pulmonary embolism.

Pulmonary fat embolism (PFE) is a common complication of blunt force traumas with bone fractures. Severe forms cause impedance to right ventricular (RV) ejection, with eventual right heart ischaemia and failure. In a prospective study, we have investigated 220 consecutive autopsy cases (73 females, 147 males, mean age 52.1 years, min 14 years, max 91 years). PFE was detected in 52 cases that were divided into three groups according to the degree of PFE (1-3). A fourth group of cases of violent death without PFE was used for comparison. In each case, histology (H&E, Masson) and immunohistochemistry (fibronectin and C5b-9) were performed on six cardiac samples (anterior, lateral and posterior wall of both ventricles). The degree of cardiac damage was registered in each sample and the mean degree of damage was calculated in each case at the RV and left ventricle (LV). Moreover, a parameter ∆ that is the difference between the mean damage at the RV and the LV was calculated in each case. The results were compared within each group and between the groups. In the present study, we could not detect prevalent RV damage in cases of high degree PFE as we did in our previous investigation. In the group PFE3 the difference of the degree of damage between the RV and LV was higher than the one observed in the groups PFE0-2 with the antibody anti-fibronectin. Prevalent right ventricular stress in cases of severe PFE may explain this observation.

Right ventricular dysfunction in children and adolescents conceived by assisted reproductive technologies.

Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.

Exaggerated pulmonary hypertension and right ventricular dysfunction in high-altitude dwellers with patent foramen ovale.

BACKGROUND: There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems. METHODS: We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure. RESULTS: The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg, P < .001) and a blunted increase in fractional area change of the right ventricle (3% [-1%, 5%] vs 7% [3%, 16%], P = .008) during mild exercise. CONCLUSIONS: These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Analysis of flow dynamics in right ventricular outflow tract.

BACKGROUND: The mechanism behind early graft failure after right ventricular outflow tract (RVOT) reconstruction is not fully understood. Our aim was to establish a three-dimensional computational fluid dynamics (CFD) model of RVOT to investigate the hemodynamic conditions that may trigger the development of intimal hyperplasia and arteriosclerosis. METHODS: Pressure, flow, and diameter at the RVOT, pulmonary artery (PA), bifurcation of the PA, and left and right PAs were measured in 10 normal pigs with a mean weight of 24.8 ± 0.78 kg. Data obtained from the experimental scenario were used for CFD simulation of pressure, flow, and shear stress profile from the RVOT to the left and right PAs. RESULTS: Using experimental data, a CFD model was obtained for 2.0 and 2.5-L/min pulsatile inflow profiles. In both velocity profiles, time and space averaged in the low-shear stress profile range from 0-6.0 Pa at the pulmonary trunk, its bifurcation, and at the openings of both PAs. These low-shear stress areas were accompanied to high-pressure regions 14.0-20.0 mm Hg (1866.2-2666 Pa). Flow analysis revealed a turbulent flow at the PA bifurcation and ostia of both PAs. CONCLUSIONS: Identified local low-shear stress, high pressure, and turbulent flow correspond to a well-defined trigger pattern for the development of intimal hyperplasia and arteriosclerosis. As such, this real-time three-dimensional CFD model may in the future serve as a tool for the planning of RVOT reconstruction, its analysis, and prediction of outcome.

Fluid dynamics simulation of right ventricular outflow tract oversizing.

OBJECTIVES: Repair of the right ventricular outflow tract (RVOT) in paediatric cardiac surgery remains challenging due to the high reoperation rate. Intimal hyperplasia and consequent arteriosclerosis is one of the most important limitation factors for graft durability. Since local shear stress and pressure are predictive elements for intimal hyperplasia and wall degeneration, we sought to determine in an oversized 12-mm RVOT model, with computed fluid dynamics simulation, the local haemodynamical factors that may explain intimal hyperplasia. This was done with the aim of identifying the optimal degree of oversizing for a 12-mm native RVOT. METHODS: Twenty domestic pigs, with a weight of 24.6 ± 0.89 kg and a native RVOT diameter of 12 ± 1.7 mm, had valve conduits of 12, 16, 18 and 20 mm implanted. Pressure and flow were measured at 75, 100 and 125% of normal flow at RVOT at the pulmonary artery, pulmonary artery bifurcation and at the left and right pulmonary arteries. Three-dimensional computed fluid dynamics (CFD) simulation in all four geometries in all flow modalities was performed. Local shear stress and pressure conditions were investigated. RESULTS: Corresponding to 75, 100 and 125% of steady-state flow, three inlet velocity profiles were obtained, 0.2, 0.29 and 0.36 m/s, respectively. At inflow velocity profiles, low shear stress areas, ranged from 0 to 2 Pa, combined with high-pressure areas ranging from 11.5 to 12.1 mmHg that were found at distal anastomosis, at bifurcation and at the ostia of the left and right pulmonary arteries in all geometries. CONCLUSIONS: In all three oversized geometries, the local reparation of shear stress and pressure in the 16-mm model showed a similar local profile as in the native 12 mm RVOT. According to these findings, we suggest oversizing the natural 12-mm RVOT by not more than 4 mm. The elements responsible for wall degeneration and intimal hyperplasia remain very similar to the conditions present in native RVOT.