Synthesis, characterization and biological analysis of the complex [VO(Hdhp)(2)] (H(2)dhp=2,3-dihydroxypyridine)

A new vanadium (IV) complex with the monoanion of 2,3-dihydroxypyridine (H(2)dhp), or 3-hydroxy-2(1H)-pyridone, was synthesized, characterized by physicochemical techniques and tested biologically. The EPR data for the [VO(Hdhp)(2)] complex in DMF are: g(x) = 1.9768, g(y) = 1.9768 and g(z) = 1.9390; A values (10(-4) cm(-1)): A(x), 59.4; A(y//), 59.4; A(z), 171.0. The vV=O band in the IR spectrum of the complex is at 986 cm(-1). The complex is paramagnetic, with mu(eff) = 1.65 BM (d(1), spin-only) at 25 degrees C. The irreversible oxidation process [V(V)/V(IV)] of the [VO(Hdhp)(2)] complex, as revealed in a cyclic voltammogram, occurs at 876 mV. The calculated molecular structure of [VO(Hdhp)(2)] shows the vanadium(IV) center in a distorted square pyramidal environment, with the oxo ligand in the apical position and the oxygen donor atoms of the Hdhp ligands in the basal positions. The ability of [VO(Hdhp)(2)] to mimic insulin, and its toxicity to hepato-biliary functions, were investigated in streptozotocin-induced diabetic rats and it was concluded that the length of treatment and the amount of [VO(Hdhp)(2)] administered were effective in reducing experimental diabetes.

Lifestyle and health status in a sample of Swedish women four years after pregnancy : a comparison of women with a history of normal pregnancy and women with a history of gestational diabetes mellitus

Background: Despite the recommendations to continue the regime of healthy food and physical activity (PA) postpartum for women with previous gestational diabetes mellitus (GDM), the scientific evidence reveals that these recommendations may not be complied to. This study compared lifestyle and health status in women whose pregnancy was complicated by GDM with women who had a normal pregnancy and delivery. Methods: The inclusion criteria were women with GDM (ICD-10: O24.4 A and O24.4B) and women with uncomplicated pregnancy and delivery in 2005 (ICD-10: O80.0). A random sample of women fulfilling the criteria (n = 882) were identified from the Swedish Medical Birth Register. A questionnaire was sent by mail to eligible women approximately four years after the pregnancy. A total of 444 women (50.8%) agreed to participate, 111 diagnosed with GDM in their pregnancy and 333 with normal pregnancy/ delivery. Results: Women with previous GDM were significantly older, reported higher body weight and less PA before the index pregnancy. No major differences between the groups were noticed regarding lifestyle at the follow-up. Overall, few participants fulfilled the national recommendations of PA and diet. At the follow-up, 19 participants had developed diabetes, all with previous GDM. Women with previous GDM reported significantly poorer self-rated health (SRH), higher level of sick-leave and more often using medication on regular basis. However, a history of GDM or having overt diabetes mellitus showed no association with poorer SRH in the multivariate analysis. Irregular eating habits, no regular PA, overweight/obesity, and regular use of medication were associated with poorer SRH in all participants. Conclusions: Suboptimal levels of PA, and fruit and vegetable consumption were found in a sample of women with a history of GDM as well as for women with normal pregnancy approximately four years after index pregnancy. Women with previous GDM seem to increase their PA after childbirth, but still they perform their PA at lower intensity than women with a history of normal pregnancy. Having GDM at index pregnancy or being diagnosed with overt diabetes mellitus at follow-up did not demonstrate associations with poorer SRH four years after delivery.

Motion Cues Analysis for Parkinson Gait Recognition

Background: Previous assessment methods for PG recognition used sensor mechanisms for PG that may cause discomfort. In order to avoid stress of applying wearable sensors, computer vision (CV) based diagnostic systems for PG recognition have been proposed. Main constraints in these methods are the laboratory setup procedures: Novel colored dresses for the patients were specifically designed to segment the test body from a specific colored background. Objective: To develop an image processing tool for home-assessment of Parkinson Gait(PG) by analyzing motion cues extracted during the gait cycles. Methods: The system is based on the idea that a normal body attains equilibrium during the gait by aligning the body posture with the axis of gravity. Due to the rigidity in muscular tone, persons with PD fail to align their bodies with the axis of gravity. The leaned posture of PD patients appears to fall forward. Whereas a normal posture exhibits a constant erect posture throughout the gait. Patients with PD walk with shortened stride angle (less than 15 degrees on average) with high variability in the stride frequency. Whereas a normal gait exhibits a constant stride frequency with an average stride angle of 45 degrees. In order to analyze PG, levodopa-responsive patients and normal controls were videotaped with several gait cycles. First, the test body is segmented in each frame of the gait video based on the pixel contrast from the background to form a silhouette. Next, the center of gravity of this silhouette is calculated. This silhouette is further skeletonized from the video frames to extract the motion cues. Two motion cues were stride frequency based on the cyclic leg motion and the lean frequency based on the angle between the leaned torso tangent and the axis of gravity. The differences in the peaks in stride and lean frequencies between PG and normal gait are calculated using Cosine Similarity measurements. Results: High cosine dissimilarity was observed in the stride and lean frequencies between PG and normal gait. High variations are found in the stride intervals of PG whereas constant stride intervals are found in the normal gait. Conclusions: We propose an algorithm as a source to eliminate laboratory constraints and discomfort during PG analysis. Installing this tool in a home computer with a webcam allows assessment of gait in the home environment.

Automatic spiral analysis for objective assessment of motor symptoms in Parkinson's disease

Objective: To develop a method for objective quantification of PD motor symptoms related to Off episodes and peak dose dyskinesias, using spiral data gathered by using a touch screen telemetry device. The aim was to objectively characterize predominant motor phenotypes (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Background: A retrospective analysis was conducted on recordings from 65 patients with advanced idiopathic PD from nine different clinics in Sweden, recruited from January 2006 until August 2010. In addition to the patient group, 10 healthy elderly subjects were recruited. Upper limb movement data were collected using a touch screen telemetry device from home environments of the subjects. Measurements with the device were performed four times per day during week-long test periods. On each test occasion, the subjects were asked to trace pre-drawn Archimedean spirals, using the dominant hand. The pre-drawn spiral was shown on the screen of the device. The spiral test was repeated three times per test occasion and they were instructed to complete it within 10 seconds. The device had a sampling rate of 10Hz and measured both position and time-stamps (in milliseconds) of the pen tip. Methods: Four independent raters (FB, DH, AJ and DN) used a web interface that animated the spiral drawings and allowed them to observe different kinematic features during the drawing process and to rate task performance. Initially, a number of kinematic features were assessed including ‘impairment’, ‘speed’, ‘irregularity’ and ‘hesitation’ followed by marking the predominant motor phenotype on a 3-category scale: tremor, bradykinesia and/or choreatic dyskinesia. There were only 2 test occasions for which all the four raters either classified them as tremor or could not identify the motor phenotype. Therefore, the two main motor phenotype categories were bradykinesia and dyskinesia. ‘Impairment’ was rated on a scale from 0 (no impairment) to 10 (extremely severe) whereas ‘speed’, ‘irregularity’ and ‘hesitation’ were rated on a scale from 0 (normal) to 4 (extremely severe). The proposed data-driven method consisted of the following steps. Initially, 28 spatiotemporal features were extracted from the time series signals before being presented to a Multilayer Perceptron (MLP) classifier. The features were based on different kinematic quantities of spirals including radius, angle, speed and velocity with the aim of measuring the severity of involuntary symptoms and discriminate between PD-specific (bradykinesia) and/or treatment-induced symptoms (dyskinesia). A Principal Component Analysis was applied on the features to reduce their dimensions where 4 relevant principal components (PCs) were retained and used as inputs to the MLP classifier. Finally, the MLP classifier mapped these components to the corresponding visually assessed motor phenotype scores for automating the process of scoring the bradykinesia and dyskinesia in PD patients whilst they draw spirals using the touch screen device. For motor phenotype (bradykinesia vs. dyskinesia) classification, the stratified 10-fold cross validation technique was employed. Results: There were good agreements between the four raters when rating the individual kinematic features with intra-class correlation coefficient (ICC) of 0.88 for ‘impairment’, 0.74 for ‘speed’, 0.70 for ‘irregularity’, and moderate agreements when rating ‘hesitation’ with an ICC of 0.49. When assessing the two main motor phenotype categories (bradykinesia or dyskinesia) in animated spirals the agreements between the four raters ranged from fair to moderate. There were good correlations between mean ratings of the four raters on individual kinematic features and computed scores. The MLP classifier classified the motor phenotype that is bradykinesia or dyskinesia with an accuracy of 85% in relation to visual classifications of the four movement disorder specialists. The test-retest reliability of the four PCs across the three spiral test trials was good with Cronbach’s Alpha coefficients of 0.80, 0.82, 0.54 and 0.49, respectively. These results indicate that the computed scores are stable and consistent over time. Significant differences were found between the two groups (patients and healthy elderly subjects) in all the PCs, except for the PC3. Conclusions: The proposed method automatically assessed the severity of unwanted symptoms and could reasonably well discriminate between PD-specific and/or treatment-induced motor symptoms, in relation to visual assessments of movement disorder specialists. The objective assessments could provide a time-effect summary score that could be useful for improving decision-making during symptom evaluation of individualized treatment when the goal is to maximize functional On time for patients while minimizing their Off episodes and troublesome dyskinesias.

Motion cue analysis for parkinsonian gait recognition

This paper presents a computer-vision based marker-free method for gait-impairment detection in Patients with Parkinson's disease (PWP). The system is based upon the idea that a normal human body attains equilibrium during the gait by aligning the body posture with Axis-of-Gravity (AOG) using feet as the base of support. In contrast, PWP appear to be falling forward as they are less-able to align their body with AOG due to rigid muscular tone. A normal gait exhibits periodic stride-cycles with stride-angle around 45o between the legs, whereas PWP walk with shortened stride-angle with high variability between the stride-cycles. In order to analyze Parkinsonian-gait (PG), subjects were videotaped with several gait-cycles. The subject's body was segmented using a color-segmentation method to form a silhouette. The silhouette was skeletonized for motion cues extraction. The motion cues analyzed were stride-cycles (based on the cyclic leg motion of skeleton) and posture lean (based on the angle between leaned torso of skeleton and AOG). Cosine similarity between an imaginary perfect gait pattern and the subject gait patterns produced 100% recognition rate of PG for 4 normal-controls and 3 PWP. Results suggested that the method is a promising tool to be used for PG assessment in home-environment.

Fatores de risco para morte em pacientes diabéticos e não diabéticos em tratamento hemodialítico

A mortalidade dos pacientes diabéticos, quando iniciam tratamento hemodialítico, ainda é muito elevada, significativamente maior do que a dos pacientes não diabéticos. As doenças cardíacas são a principal causa de morte nestes pacientes. O diabetes, por si só, está associado a uma alta prevalência de hipertensão, doença cardiovascular e insuficiência cardíaca, resultando em morbi-mortalidade significativas. Tradicionalmente, a mortalidade tem sido associada à cardiopatia isquêmica. A mortalidade cardiovascular, entretanto, não está relacionada apenas à isquemia, mas também à insuficiência cardíaca e à morte súbita. O objetivo deste estudo foi analisar o papel da doença cardiovascular como fator prognóstico para a morte de pacientes diabéticos e não diabéticos, que iniciam hemodiálise, levando em consideração outros fatores. Este foi um estudo prospectivo de uma coorte de 40 pacientes diabéticos e 28 não diabéticos, que iniciaram programa de hemodiálise, de agosto de 1996 a junho de 1999, em 5 hospitais de Porto Alegre, Brasil. O tempo total de acompanhamento foi de 4,25 anos. A avaliação inicial, realizada entre o 20 e o 30 mês de hemodiálise, incluiu: um questionário com características demográficas, história do diabetes e suas complicações, história de hipertensão e acidente vascular cerebral; o exame físico incluindo avaliação nutricional e exame oftalmológico; e avaliação laboratorial com medidas de parâmetros nutricionais, bioquímicos, hormonais, perfil lipídico, e controle metabólico do diabetes, além da avaliação da adequação da diálise. Para a avaliação cardiovascular foram utilizados: questionário Rose, ECG em repouso, cintilografia em repouso e sob dipiridamol, e ecocardiograma bi-dimensional e com Doppler. A mortalidade foi analisada ao final dos 51 meses, e as causas de morte, definidas pelos registros médicos, atestados de óbito ou informações do médico assistente ou familiar. Na análise estatística, foram empregados o teste t de Student, o qui-quadrado (χ2) ou teste exato de Fisher. Para a análise da sobrevida, o método de Kaplan-Meier foi utilizado, e, para identificar os principais fatores associados à mortalidade, construiu-se um modelo de regressão múltipla de Cox. O nÍvel de significância adotado foi de 5%. Ao final do estudo, os pacientes diabéticos tiveram um índice de mortalidade significativamente mais elevado do que os pacientes sem diabetes (47,5% vs. 7,1%; P=0,0013, log rank test). Na análise de Cox, o padrão pseudonormal ou restritivo de disfunção diastólica esteve associado a um risco de 3,2 (IC 95%:1,2-8,8; P=0,02), e a presença de diabetes, a um risco de 4,7 (IC 95%:1,03-21,4; P=0,04) para a morte. Concluiu-se que a disfunção diastólica do ventrículo esquerdo foi o principal preditor de mortalidade nesta coorte de pacientes que estão iniciando tratamento hemodialítico.

Internationalization of SME and entry mode choice in Brazil: the case study of Ameco, a French SME

O objetivo da pesquisa é analisar, para uma PME francesa, a atratividade de dois mercados-alvo no Brasil, a fim de apoiar a tomada de decisão do CEO sobre o investimento futuro. Para enfrentar a crise da União Europeia, muitas PMEs francesas estão procurando novas oportunidades em todo o mundo, especialmente nos países BRIC. Na verdade, o Brasil parece ser um mercado promissor, oferecendo inúmeras oportunidades de crescimento. No entanto, em comparação com as empresas multinacionais tradicionais, as PMEs têm de lidar com a falta de recursos e de poder de mercado. Ir global é arriscado e caro para as PMEs; o que implica avaliar cuidadosamente a viabilidade da implementação de um investimento estrangeiro. A análise revelou que o Brasil é um mercado de aproximadamente 30 milhões de euros, nos próximos 10 anos. Este é definitivamente um mercado promissor para uma empresa como AMECO. Levando em conta esses critérios, AMECO deve abrir um escritório de representação no próximo ano para angariar novos clientes e assinar novos contratos.

Factors affecting the technical efficiency of production of the Brazilian banking system : a comparison of four statistical models in the context of data envelopment analysis

This paper uses an output oriented Data Envelopment Analysis (DEA) measure of technical efficiency to assess the technical efficiencies of the Brazilian banking system. Four approaches to estimation are compared in order to assess the significance of factors affecting inefficiency. These are nonparametric Analysis of Covariance, maximum likelihood using a family of exponential distributions, maximum likelihood using a family of truncated normal distributions, and the normal Tobit model. The sole focus of the paper is on a combined measure of output and the data analyzed refers to the year 2001. The factors of interest in the analysis and likely to affect efficiency are bank nature (multiple and commercial), bank type (credit, business, bursary and retail), bank size (large, medium, small and micro), bank control (private and public), bank origin (domestic and foreign), and non-performing loans. The latter is a measure of bank risk. All quantitative variables, including non-performing loans, are measured on a per employee basis. The best fits to the data are provided by the exponential family and the nonparametric Analysis of Covariance. The significance of a factor however varies according to the model fit although it can be said that there is some agreements between the best models. A highly significant association in all models fitted is observed only for nonperforming loans. The nonparametric Analysis of Covariance is more consistent with the inefficiency median responses observed for the qualitative factors. The findings of the analysis reinforce the significant association of the level of bank inefficiency, measured by DEA residuals, with the risk of bank failure.

We're Chained: an analysis of systemic risk in finance

This dissertation presents two papers on how to deal with simple systemic risk measures to assess portfolio risk characteristics. The first paper deals with the Granger-causation of systemic risk indicators based in correlation matrices in stock returns. Special focus is devoted to the Eigenvalue Entropy as some previous literature indicated strong re- sults, but not considering different macroeconomic scenarios; the Index Cohesion Force and the Absorption Ratio are also considered. Considering the S&P500, there is not ev- idence of Granger-causation from Eigenvalue Entropies and the Index Cohesion Force. The Absorption Ratio Granger-caused both the S&P500 and the VIX index, being the only simple measure that passed this test. The second paper develops this measure to capture the regimes underlying the American stock market. New indicators are built using filtering and random matrix theory. The returns of the S&P500 is modelled as a mixture of normal distributions. The activation of each normal distribution is governed by a Markov chain with the transition probabilities being a function of the indicators. The model shows that using a Herfindahl-Hirschman Index of the normalized eigenval- ues exhibits best fit to the returns from 1998-2013.

Multivariate analysis for the classification and differentiation of Madeira wines according to main grape varieties

In order to differentiate and characterize Madeira wines according to main grape varieties, the volatile composition (higher alcohols, fatty acids, ethyl esters and carbonyl compounds) was determined for 36 monovarietal Madeira wine samples elaborated from Boal, Malvazia, Sercial and Verdelho white grape varieties. The study was carried out by headspace solid-phase microextraction technique (HS-SPME), in dynamic mode, coupled with gas chromatography–mass spectrometry (GC–MS). Corrected peak area data for 42 analytes from the above mentioned chemical groups was used for statistical purposes. Principal component analysis (PCA) was applied in order to determine the main sources of variability present in the data sets and to establish the relation between samples (objects) and volatile compounds (variables). The data obtained by GC–MS shows that the most important contributions to the differentiation of Boal wines are benzyl alcohol and (E)-hex-3-en-1-ol. Ethyl octadecanoate, (Z)-hex-3-en-1-ol and benzoic acid are the major contributions in Malvazia wines and 2-methylpropan-1-ol is associated to Sercial wines. Verdelho wines are most correlated with 5-(ethoxymethyl)-furfural, nonanone and cis-9-ethyldecenoate. A 96.4% of prediction ability was obtained by the application of stepwise linear discriminant analysis (SLDA) using the 19 variables that maximise the variance of the initial data set.

Analysis of testosterone pulsatility in women with ovulatory menstrual cycles

Objetivo: Avaliar o padrão pulsátil da secreção da testosterona em mulheres normais. Métodos: Oito mulheres saudáveis com ciclos ovulatórios foram selecionadas. Amostras sanguíneas foram coletadas a cada dez minutos durante seis horas, começando entre 7 e 8 h da manhã, após dez horas de jejum, nas três fases do ciclo menstrual: folicular média (Dia 7), folicular tardia (Dia 12) e lútea (Dia 21). Foram mensurados: testosterona, LH e, no basal, também SHBG. Resultados: A frequência dos pulsos de testosterona, média da amplitude do pulso, porcentagem do incremento da amplitude, duração e intervalos dos pulsos foram similares nas três fases (p > 0,05). A pulsatilidade do LH foi estatisticamente diferente entre as três fases (p < 0,001), caracterizando padrão característico do ciclo ovulatório normal. Conclusões: Esses dados aumentam o conhecimento sobre o padrão de secreção da testosterona no ciclo menstrual humano e representam uma contribuição para a investigação clínica, tanto no hiperandrogenismo como na síndrome de insuficiência androgênica __________________________________________________ ABSTRACT Objective: To evaluate the pattern of the pulsatile secretion of testosterone in normal menstrual cycle. Methods: Eight healthy women with ovulatory menstrual cycles were enrolled. Blood samples were collected at ten-minute intervals for six hours, starting between 7 and 8 am, after a ten-hour fasting, in three phases: mid-follicular (Day 7), late follicular (Day 12) and mid-luteal phase (Day 21). Samples were assayed for testosterone, LH and the baseline also for SHBG. Results: Testosterone pulse frequency, mean amplitude pulse, percentage of increment in pulse amplitude, mean duration of pulses and pulse interval were similar in the three phases. LH pulsatility was statistically different among the three phases (p < 0.001) representing normal ovulatory cycles. Conclusions: These data increase the knowledge about the testosterone secretion profile in the human menstrual cycle and can be used as a contribution to clinical investigation in both hyperandrogenism and androgen insufficiency syndrome

Retinal nerve fiber layer analysis using GDx® in 49 patients with chronic phase DUSN

To describe retinal nerve fiber layer changes in late-stage diffuse unilateral subacute neuroretinitis eyes and compare these results with healthy eyes observed through nerve fiber analyzer (GDx®). Methods: This is a retrospective case-control study in which 49 eyes in late-stage diffuse unilateral subacute neuroretinitis were examined from May/97 to December/ 01. First, eyes with diffuse unilateral subacute neuroretinitis and healthy contralateral eyes (Control Group I) were statistically matched. Subsequently, eyes with diffuse unilateral subacute neuroretinitis were compared with eyes of healthy patients (Control Group II). Results: Eyes from Control Groups I and II had higher relative frequency of “within normal limits” status. Eyes from the diffuse unilateral subacute neuroretinitis (DUSN) Group had higher frequency of “outside normal limits” and “borderline” status. Control Groups I and II had absolute values different from the DUSN Group regarding all parameters (p<0.05), except for Symmetry in Control Groups I and II, Average thickness and Superior Integral in control group II. Conclusion: Patients with late-stage diffuse unilateral subacute neuroretinitis presented presumed decrease in nerve fiber layer thickness shown by GDx®. Retinal zones with larger vascular support and larger amount of nerve fibers presented higher decrease in the delay of the reflected light measured by the nerve fiber analyzer

Purification and preliminary crystallographic analysis of a new Lys49-PLA2 from B-jararacussu

BjVIII is a new myotoxic Lys49-PLA2 isolated from Bothrops jararacussu venom that exhibits atypical effects on human platelet aggregation. To better understand the mode of action of BjVIII, crystallographic studies were initiated. Two crystal forms were obtained, both containing two molecules in the asymmetric unit (ASU). Synchrotron radiation diffraction data were collected to 2.0 angstrom resolution and 1.9 angstrom resolution for crystals belonging to the space group P2(1)2(1)2(1) (a = 48.4 angstrom, b = 65.3 angstrom, c = 84.3 angstrom) and space group P3(1)21 (a = b = 55.7 angstrom, c = 127.9 angstrom), respectively. Refinement is currently in progress and the refined structures are expected to shed light on the unusual platelet aggregation activity observed for BjVIII.

Síndrome metabólica e fatores associados: estudo comparativo com mulheres que apresentaram pré-eclâmpsia e gravidez normal, acompanhadas cinco anos após o parto

Preeclampsia is defined as an extremely serious complication of the pregnancy-puerperium cycle with delayed emergence of cardiovascular risk factors, including metabolic syndrome. The research aimed estimate the prevalences of metabolic syndrome and associated factors in women with preeclampsia and normal pregnancy followed five years after childbirth. This is a cross-sectional observational study using a quantitative approach, conducted at a maternity school in the city of Natal in Rio Grande do Norte state. The sample was composed of 70 women with previous preeclampsia and 75 normal selected by simple random probability sampling. Subjects were analyzed for sociodemographic, obstetric, clinical, anthropometric and biochemical parameters. International Diabetes Federation criteria were adopted to diagnose metabol ic syndrome. The Kolmogorov-Smirnov, Mann-Whitney, Student s t, Pearson s chi-squared, and Fisher s exact tests, in addition to simple logistic regression, were used for data analysis, at a 5% significance level (p ≤ 0.05). Statistical tests demonstrated elevated body mass index (p = 0.001), predominance of family history of diabetes mellitus (p = 0.022) and significantly higher prevalence of metabolic syndrome in the preeclampsia group (37.1%) when compared to normal (22.7%) (p = 0.042). Intergroup comparison showed a high number of metabolic syndrome components in women with previous preeclampsia. Altered systolic and diastolic blood pressure (p < 0.001) was the most prevalent, followed by low concentrations of high-density lipoproteins (p = 0.049), and hyperglycemia (p=0.030). There was a predominance of the metabolic syndrome in women with schooling 0-9 years (42.4%) (p = 0.005), body mass index above 30Kg.m 2 (52.3%) (p < 0.001), uric acid high (62.5%) (p = 0.050 and family history of hypertension (38.5%) (p< 0.001). Multivariate analysis of the data showed that the body mass index above 30 kg.m2, education level less than 10 years of study (p < 0.001) and family history of hypertension (p = 0.002) remained associated with the metabolic syndrome after multivariate analysis of the data. It is considered Women with previous preeclampsia exhibited high prevalence of metabolic syndrome and their individual components in relation to normal, especially, altered systolic and diastolic blood pressure, low concentrations of high-density lipoproteins and hyperglycemia. The factors associated to this ou tcome were obesity, less than 10 years of schooling, and family history of hypertension. Overall, this study identified young women with a history of PE exposed to a higher cardiovascular risk than normal