Automatic segmentation of the great arteries for computational hemodynamic assessment.

BACKGROUND: Computational fluid dynamics (CFD) is increasingly used for the assessment of blood flow conditions in patients with congenital heart disease (CHD). This requires patient-specific anatomy, typically obtained from segmented 3D cardiovascular magnetic resonance (CMR) images. However, segmentation is time-consuming and requires expert input. This study aims to develop and validate a machine learning (ML) method for segmentation of the aorta and pulmonary arteries for CFD studies. METHODS: 90 CHD patients were retrospectively selected for this study. 3D CMR images were manually segmented to obtain ground-truth (GT) background, aorta and pulmonary artery labels. These were used to train and optimize a U-Net model, using a 70-10-10 train-validation-test split. Segmentation performance was primarily evaluated using Dice score. CFD simulations were set up from GT and ML segmentations using a semi-automatic meshing and simulation pipeline. Mean pressure and velocity fields across 99 planes along the vessel centrelines were extracted, and a mean average percentage error (MAPE) was calculated for each vessel pair (ML vs GT). A second observer (SO) segmented the test dataset for assessment of inter-observer variability. Friedman tests were used to compare ML vs GT, SO vs GT and ML vs SO metrics, and pressure/velocity field errors. RESULTS: The network's Dice score (ML vs GT) was 0.945 (interquartile range: 0.929-0.955) for the aorta and 0.885 (0.851-0.899) for the pulmonary arteries. Differences with the inter-observer Dice score (SO vs GT) and ML vs SO Dice scores were not statistically significant for either aorta or pulmonary arteries (p = 0.741, p = 0.061). The ML vs GT MAPEs for pressure and velocity in the aorta were 10.1% (8.5-15.7%) and 4.1% (3.1-6.9%), respectively, and for the pulmonary arteries 14.6% (11.5-23.2%) and 6.3% (4.3-7.9%), respectively. Inter-observer (SO vs GT) and ML vs SO pressure and velocity MAPEs were of a similar magnitude to ML vs GT (p > 0.2). CONCLUSIONS: ML can successfully segment the great vessels for CFD, with errors similar to inter-observer variability. This fast, automatic method reduces the time and effort needed for CFD analysis, making it more attractive for routine clinical use.

Difference in ambient-personal exposure to PM2.5 and its inflammatory effect in local residents in urban and peri-urban Beijing, China: results of the AIRLESS project.

Measurement of ambient fine particulate matter (PM2.5) is often used as a proxy of personal exposure in epidemiological studies. However, the difference between personal and ambient exposure, and whether it biases the estimates of health effects remain unknown. Based on an epidemiological study (AIRLESS) and simultaneously launched intensive monitoring campaigns (APHH), we quantified and compared the personal and ambient exposure to PM2.5 and the related health impact among residents in Beijing, China. In total, 123 urban and 128 peri-urban non-smoking participants were recruited from two well-established cohorts in Beijing. During winter 2016 and summer 2017, each participant was instructed to carry a validated personal air monitor (PAM) to measure PM2.5 concentration at high spatiotemporal resolution for seven consecutive days in each season. Multiple inflammatory biomarkers were measured, including exhaled NO, blood monocytes counts and C-reactive protein. Linear mixed-effect models were used for the associations between exposure and health outcomes with adjustment for confounders. The average level of daily personal exposure to PM2.5 was consistently lower than using corresponding ambient concentration, and the difference is greater during the winter. The personal to ambient (P/A) ratio of exposure to PM2.5 exhibited an exponentially declining trend, and showed larger variations when ambient PM2.5 levels < 25 µg m-3. Personal exposure to PM2.5 was significantly associated with the increase in respiratory and systemic inflammatory biomarkers; however, the associations were weaker or became insignificant when ambient concentrations were used. Exposure to ambient PM2.5 might not be a good proxy to estimate the health effect of exposure to personal PM2.5.

Is traditional perinatal autopsy needed after detailed fetal ultrasound and post-mortem MRI?

OBJECTIVE: To determine the additional yield from autopsy following prenatal ultrasound and post-mortem magnetic resonance imaging (PMMR) for structural abnormalities. METHOD: PMMR was performed on consecutive fetuses over a 6-year period. Prenatal ultrasound and PMMR findings were categorised as concordant, partially concordant or discordant findings. The yield of new and clinically significant information from autopsy was assessed. Diagnostic accuracies for both modalities were calculated, using autopsy as reference standard. RESULTS: Our study consisted of 81 fetuses. PMMR and prenatal ultrasound findings were concordant in 44/81 (54.3%), partially concordant in 26/81 (32.1%) and discordant in 11/81 (13.6%) cases. In 19/81 cases (23%), autopsy provided additional information, which appeared clinically significant in 12 cases. In 10 of those 12 cases, there was discordance between PMMR and ultrasound. In only 2 of 44 cases where ultrasound and PMMR were concordant, did autopsy provide clinically significant information. Diagnostic accuracy rates for ultrasound were sensitivity of 76.8% (66.6%, 84.6%), specificity of 92.5% (88.9%, 95.0%). For PMMR the sensitivity was 79.0% (68.9%, 86.5%), specificity 97.9% (95.5%, 99.0%). PMMR had a significantly higher concordance rate with autopsy than ultrasound (89.0 vs 93.8%; P < .001). CONCLUSION: Where PMMR and ultrasound are concordant, there is little additional yield from autopsy.

Learning effect on perinatal post-mortem magnetic resonance imaging reporting: single reporter diagnostic accuracy of 200 cases.

OBJECTIVE: The objective of the study is to compare diagnostic accuracy of perinatal post-mortem magnetic resonance (PMMR) imaging against conventional autopsy, when reported by a single-blinded observer for all organ systems following a period of initial experience. METHODS: We compared pre-autopsy PMMR with conventional autopsy for the detection of (1) major pathological abnormalities related to the cause of death and (2) all diagnostic findings in five different body organ systems. PMMR was reported blinded to autopsy findings. RESULTS: In 201 cases, 123/146 (84.2%) of major abnormalities were identified by PMMR. Overall diagnostic accuracy of PMMR was 89.6% [95% confidence interval (CI): 84.3, 93.2%] across all cases, with high concordance 91.8% (95% CI: 89.9, 93.4%) across most organ systems. Our study showed higher concordance than single reporter statistics previously reported in neurological [92.2% vs 73.8%; diff 18.4% (95% CI: 11.0, 25.4%) p < 0.01] and thoracic systems [93.7% vs 81.2%; diff 12.5% (95% CI: 6.3, 18.4%) p < 0.01] and slightly better overall [91.8% vs 87.1%; diff 4.7% (95% CI: 2.1, 7.3%) p < 0.01]. CONCLUSION: The PMMR examinations can be reliably reported by a single radiologist, following a period of experience and training with this specific modality, with high-diagnostic accuracy for all organ systems. © 2017 John Wiley & Sons, Ltd.

Comparison of diagnostic performance for perinatal and paediatric post-mortem imaging: CT versus MRI.

OBJECTIVES: To compare the diagnostic yield of whole-body post-mortem computed tomography (PMCT) imaging to post-mortem magnetic resonance (PMMR) imaging in a prospective study of fetuses and children. METHODS: We compared PMCT and PMMR to conventional autopsy as the gold standard for the detection of (a) major pathological abnormalities related to the cause of death and (b) all diagnostic findings in five different body organ systems. RESULTS: Eighty two cases (53 fetuses and 29 children) underwent PMCT and PMMR prior to autopsy, at which 55 major abnormalities were identified. Significantly more PMCT than PMMR examinations were non-diagnostic (18/82 vs. 4/82; 21.9 % vs. 4.9 %, diff 17.1 % (95 % CI 6.7, 27.6; p < 0.05)). PMMR gave an accurate diagnosis in 24/55 (43.64 %; 95 % CI 31.37, 56.73 %) compared to 18/55 PMCT (32.73 %; 95 % CI 21.81, 45.90). PMCT was particularly poor in fetuses <24 weeks, with 28.6 % (8.1, 46.4 %) more non-diagnostic scans. Where both PMCT and PMMR were diagnostic, PMMR gave slightly higher diagnostic accuracy than PMCT (62.8 % vs. 59.4 %). CONCLUSION: Unenhanced PMCT has limited value in detection of major pathology primarily because of poor-quality, non-diagnostic fetal images. On this basis, PMMR should be the modality of choice for non-invasive PM imaging in fetuses and children. KEY POINTS: • Overall 17.1 % more PMCT examinations than PMMR were non-diagnostic • 28.6 % more PMCT were non-diagnostic than PMMR in fetuses <24 weeks • PMMR detected almost a third more pathological abnormalities than PMCT • PMMR gave slightly higher diagnostic accuracy when both were diagnostic.

Numerical model of a valvuloplasty balloon: in vitro validation in a rapid-prototyped phantom.

BACKGROUND: Patient-specific simulations can provide insight into the mechanics of cardiovascular procedures. Amongst cardiovascular devices, non-compliant balloons are used in several minimally invasive procedures, such as balloon aortic valvuloplasty. Although these balloons are often included in the computer simulations of these procedures, validation of the balloon behaviour is often lacking. We therefore aim to create and validate a computational model of a valvuloplasty balloon. METHODS: A finite element (FE) model of a valvuloplasty balloon (Edwards 9350BC23) was designed, including balloon geometry and material properties from tensile testing. Young's Modulus and distensibility of different rapid prototyping (RP) rubber-like materials were evaluated to identify the most suitable compound to reproduce the mechanical properties of calcified arteries in which such balloons are likely to be employed clinically. A cylindrical, simplified implantation site was 3D printed using the selected material and the balloon was inflated inside it. The FE model of balloon inflation alone and its interaction with the cylinder were validated by comparison with experimental Pressure-Volume (P-V) and diameter-Volume (d-V) curves. RESULTS: Root mean square errors (RMSE) of pressure and diameter were RMSE P = 161.98 mmHg (3.8 % of the maximum pressure) and RMSE d = 0.12 mm (<0.5 mm, within the acquisition system resolution) for the balloon alone, and RMSE P = 94.87 mmHg (1.9 % of the maximum pressure) and RMSE d = 0.49 mm for the balloon inflated inside the simplified implantation site, respectively. CONCLUSIONS: This validated computational model could be used to virtually simulate more realistic valvuloplasty interventions.

Diffusion-weighted perinatal postmortem magnetic resonance imaging as a marker of postmortem interval.

OBJECTIVE: To evaluate perinatal body organ apparent diffusion coefficient (ADC) values at postmortem magnetic resonance imaging (PMMR) in order to evaluate postmortem changes. METHODS: Postmortem diffusion-weighted imaging (DWI) of the thorax and abdomen were performed with diffusion gradient values b = 0, 500, and 1000 s/mm(2) on 15 foetal and childhood cases (mean 33.3 ± 7.8 weeks gestation) compared to 44 live infants (mean age 75.5 ± 53.4 days). Mean ADC values were calculated from regions of interest (ROIs) for the lungs, liver, spleen and renal cortex, compared to normative live infantile body ADC values of similar gestational age. RESULTS: Mean ADC values were significantly lower in postmortem cases than in normal controls for liver (0.88 10(-3) mm(2)/s ± SD 0.39 vs. 1.13 ± 0.13; p < 0.05) and renal cortex (0.85 ± 0.26 vs. 1.19 ± 0.13; p < 0.05) but not spleen or muscle. Mean lung ADC values were significantly higher than normal controls (1.06 ± 0.18 vs. 0 ± 0; p < 0.001), and there was a significant correlation between postmortem interval and lung ADC (R(2) = 0.55). CONCLUSION: Lung PMMR ADC values are related to postmortem interval, making them a potential marker of time since death. Further research is needed to understand the organ-specific changes which occur in the postmortem period. KEY POINTS: • Liver and spleen PM ADC values were lower than controls. • Lung ADC changes correlate with PM interval. • These findings may be useful in medicolegal cases.

Integrating modelling and smart sensors for environmental and human health.

Sensors are becoming ubiquitous in everyday life, generating data at an unprecedented rate and scale. However, models that assess impacts of human activities on environmental and human health, have typically been developed in contexts where data scarcity is the norm. Models are essential tools to understand processes, identify relationships, associations and causality, formalize stakeholder mental models, and to quantify the effects of prevention and interventions. They can help to explain data, as well as inform the deployment and location of sensors by identifying hotspots and areas of interest where data collection may achieve the best results. We identify a paradigm shift in how the integration of models and sensors can contribute to harnessing 'Big Data' and, more importantly, make the vital step from 'Big Data' to 'Big Information'. In this paper, we illustrate current developments and identify key research needs using human and environmental health challenges as an example.

Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study.

BACKGROUND: Post-mortem MRI is a potential diagnostic alternative to conventional autopsy, but few large prospective studies have compared its accuracy with that of conventional autopsy. We assessed the accuracy of whole-body, post-mortem MRI for detection of major pathological lesions associated with death in a prospective cohort of fetuses and children. METHODS: In this prospective validation study, we did pre-autopsy, post-mortem, whole-body MRI at 1·5 T in an unselected population of fetuses (≤24 weeks' or >24 weeks' gestation) and children (aged <16 years) at two UK centres in London between March 1, 2007 and Sept 30, 2011. With conventional autopsy as the diagnostic gold standard, we assessed MRI findings alone, or in conjunction with other minimally invasive post-mortem investigations (minimally invasive autopsy), for accuracy in detection of cause of death or major pathological abnormalities. A radiologist and pathologist who were masked to the autopsy findings indicated whether the minimally invasive autopsy would have been adequate. The primary outcome was concordance rate between minimally invasive and conventional autopsy. FINDINGS: We analysed 400 cases, of which 277 (69%) were fetuses and 123 (31%) were children. Cause of death or major pathological lesion detected by minimally invasive autopsy was concordant with conventional autopsy in 357 (89·3%, 95% CI 85·8-91·9) cases: 175 (94·6%, 90·3-97·0) of 185 fetuses at 24 weeks' gestation or less, 88 (95·7%, 89·3-98·3) of 92 fetuses at more than 24 weeks' gestation, 34 (81·0%, 66·7-90·0) [corrected] of 42 newborns aged 1 month or younger, 45 (84·9%, 72·9-92·1) of 53 infants aged older than 1 month to 1 year or younger, and 15 (53·6%, 35·8-70·5) of 28 children aged older than 1 year to 16 years or younger. The dedicated radiologist or pathologist review of the minimally invasive autopsy showed that in 165 (41%) cases a full autopsy might not have been needed; in these cases, concordance between autopsy and minimally invasive autopsy was 99·4% (96·6-99·9). INTERPRETATION: Minimally invasive autopsy has accuracy similar to that of conventional autopsy for detection of cause of death or major pathological abnormality after death in fetuses, newborns, and infants, but was less accurate in older children. If undertaken jointly by pathologists and radiologists, minimally invasive autopsy could be an acceptable alternative to conventional autopsy in selected cases. FUNDING: Policy research Programme, Department of Health, UK.

Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children.

OBJECTIVES: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy. METHODS: Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded to the other dataset. RESULTS: Of 400 non-cardiac thoracic abnormalities, 113 (28 %) were found at autopsy. Overall sensitivity and specificity (95 % confidence interval) of PMMR for any thoracic pathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7, 89.2) respectively, with positive predictive value (PPV) 53.7 % (42.9, 64.0) and negative predictive value (NPV) 77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1, 76.2). PMMR was most sensitive at detecting anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection. CONCLUSIONS: PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities. KEY POINTS: • PMMR has relatively poor diagnostic detection rates for common intrathoracic pathology • The moderate NPV suggests that normal PMMR appearances exclude most important abnormalities • Lung sampling at autopsy remains the "gold standard" for pulmonary pathology.

Diagnostic accuracy of postmortem MRI for musculoskeletal abnormalities in fetuses and children.

OBJECTIVES: The aim of this study was to compare the diagnostic accuracy of postmortem magnetic resonance (PMMR) imaging specifically for musculoskeletal pathology in fetuses and children, compared with conventional autopsy, with radiographic and histopathology assessment. METHODS: Institutional ethics approval and parental consent was obtained. A total of 400 cases underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data, respectively. RESULTS: A total of 400 cases were reported, with 277 (69%) fetuses (185 ≤24 weeks' gestation and 92 >24 weeks' gestation) and 123 children (42 newborns aged <1 month, 53 infants ≤12 months and 28 children ≤16 years). Musculoskeletal (MSK) abnormalities were found at autopsy in 47/400 (11.7%). Overall sensitivity and specificity (with 95% confidence interval) of PMMR for MSK pathology were 51.1% (37.0, 65.0) and 98.2% (96.2, 99.2), with positive and negative predictive values of 79.3% (61.6, 90.2) and 93.8% (90.8, 95.9), respectively. Overall accuracy between PMMR and autopsy for MSK abnormalities was 92.7% (89.7, 94.9). In some cases, PMMR detected MSK abnormalities not routinely examined for or detected at traditional autopsy. CONCLUSION: Minimally invasive autopsy has good diagnostic accuracy for the exclusion of MSK abnormalities, but sensitivity is relatively poor. When PMMR is used with clinical examination and skeletal radiographs, all skeletal and soft tissue abnormalities of clinical significance are likely to be detected, even if not directly relevant to the cause of death.

Short-term air pollution and greenness exposures on oxidative stress in urban and peri-urban residents in Beijing: A part of AIRLESS study.

BACKGROUND: Exposure to air pollution has been associated with increased risks of cardiopulmonary diseases, cancer, and mortality, whereas residing near green spaces may reduce the risks. However, limited research explores their combined effect on oxidative stress. METHODS: A total of 251 participants with multi-time measurements were included in the longitudinal-designed study. Personal gaseous air pollutants (CO, NO, NO2, and O3,) and particulate pollution (PM1, PM2.5, and PM10) were measured and followed in two 7-day windows while ambient exposure levels and urine samples were collected simultaneously. Participants' Normalized Difference Vegetation Index (NDVI) was estimated and used to represent greenness exposure. Urinary oxidative stress biomarkers include free malondialdehyde (MDA), total MDA, and 8-hydroxydeoxyguanosine (8-OHdG). Linear mixed-effects models were used to independently and jointly estimate the associations of greenness and air pollution with oxidative stress biomarkers. RESULTS: We found consistent positive associations of personal ozone (O3) exposure with 8-OHdG percent changes, and this association was modified by gender and outdoor activity frequency. Consistent positive associations of personal lag 2-day carbon monoxide (CO) exposure with the percent changes of the three oxidative stress biomarkers were significant. We additionally observed that individuals who lived in greener areas had lower levels of urinary-free and total MDA. Participants in the highest NDVI tertile had 0.38 and 0.46 lower free and total MDA levels, [95 % CI: (-0.70, -0.05) and (-0.78, -0.13)], compared to the lowest NDVI tertile. There was also evidence indicating the modification effects by area, education, and outdoor activity frequency on associations between NDVI exposure and creatinine adjusted free MDA (all Pfor interaction < 0.05). Additional greenness modification effects on personal O3 exposure with urinary 8-OHdG was observed. CONCLUSION: Our study provides biological evidence of the modification effect of the built environment on the impact of air pollution.

Molecular composition of boreal forest aerosol from Hyytiälä, Finland, using ultrahigh resolution mass spectrometry.

Organic compounds are important constituents of fine particulate matter (PM) in the troposphere. In this study, we applied direct infusion nanoelectrospray (nanoESI) ultrahigh resolution mass spectrometry (UHR-MS) and liquid chromatography LC/ESI-UHR-MS for the analysis of the organic fraction of PM1 aerosol samples collected over a two week period at a boreal forest site (Hyytiälä), southern Finland. Elemental formulas (460-730 in total) were identified with nanoESI-UHR-MS in the negative ionization mode and attributed to organic compounds with a molecular weight below 400. Kendrick Mass Defect and Van Krevelen approaches were used to identify compound classes and mass distributions of the detected species. The molecular composition of the aerosols strongly varied between samples with different air mass histories. An increased number of nitrogen, sulfur, and highly oxygenated organic compounds was observed during the days associated with continental air masses. However, the samples with Atlantic air mass history were marked by a presence of homologous series of unsaturated and saturated C12-C20 fatty acids suggesting their marine origin. To our knowledge, we show for the first time that the highly detailed chemical composition obtained from UHR-MS analyses can be clearly linked to meteorological parameters and trace gases concentrations that are relevant to atmospheric oxidation processes. The additional LC/ESI-UHR-MS analysis revealed 29 species, which were mainly attributed to oxidation products of biogenic volatile compounds BVOCs (i.e., α,ß-pinene, Δ3-carene, limonene, and isoprene) supporting the results from the direct infusion analysis.

Multiparametric mapping in post-mortem perinatal MRI: a feasibility study.

OBJECTIVES: To demonstrate feasibility of a 3 T multiparametric mapping (MPM) quantitative pipeline for perinatal post-mortem MR (PMMR) imaging. METHODS: Whole body quantitative PMMR imaging was acquired in four cases, mean gestational age 34 weeks, range (29-38 weeks) on a 3 T Siemens Prisma scanner. A multicontrast protocol yielded proton density, T1 and magnetic transfer (MT) weighted multi-echo images obtained from variable flip angle (FA) 3D fast low angle single-shot (FLASH) acquisitions, radiofrequency transmit field map and one B0 field map alongside four MT weighted acquisitions with saturation pulses of 180, 220, 260 and 300 degrees were acquired, all at 1 mm isotropic resolution. RESULTS: Whole body MPM was achievable in all four foetuses, with R1, R2*, PD and MT maps reconstructed from a single protocol. Multiparametric maps were of high quality and show good tissue contrast, especially the MT maps. CONCLUSION: MPM is a feasible technique in a perinatal post-mortem setting, which may allow quantification of post-mortem change, prior to being evaluated in a clinical setting. ADVANCES IN KNOWLEDGE: We have shown that the MPM sequence is feasible in PMMR imaging and shown the potential of MT imaging in this setting.

Mobility of arsenic, chromium and copper arising from soil application of stabilised aggregates made from contaminated wood ash.

Stabilized cementitious aggregates AG were produced from wood ashes containing ∼10,000 mg kg-1 As, Cr and Cu, then amended to two agricultural pasture soils. Metal(loid) leaching (column tests), mobility (pore water extracts) and uptake to ryegrass was determined, comparing raw ashes with aggregates. Risk modeling was applied to selected data to inform wider discussion of the experimental results. Under rapid leaching (7 h) AG 2 (pre-strengthened with CO2) outperformed AG 1 in suppressing soluble metal(loid) removal. During prolonged leaching (12d) both aggregates were susceptible to mild dissolution/release of metal(loid)s upon acidification. Pore water sampled from the pot test indicated that Cr was generally most mobile, As least so, reduced furthest by AG 2. Risk modelling, based on pot experimental data, demonstrated soil specific accumulation of As in beef muscle and milk, being furthest reduced (compared to the raw ash addition) by AG 2 in soil A, but increased in soil B by the same treatment. The results of this study indicate that a reduction in soluble As, Cr and Cu can be achieved through cementitious aggregation of wood ashes, though the extent is metal(loid) specific when amended to soils. Pre-testing under local soil conditions before field application would be required to ensure that metal(loid) mobility remained suppressed.

Class targeted metabolomics: ESI ion trap screening methods for glucosinolates based on MSn fragmentation.

Glucosinolates are naturally occurring anionic secondary plant metabolites incorporating a thioglucosidic link to the carbon of a sulphonated oxime. There are a large number of naturally occurring glucosinolates and they are found in relatively large quantities in many plant species within the family Crucifereae. These metabolites are of interest for both their anticancer and flavour properties and in the study of nitrogen and sulphur metabolism in model plants such as Arabidopsis. Parent ion mapping is an analytical mass spectrometry approach that allows rapid assessment of glucosinolate content. Ion mapping proved to be highly sensitive and the glucosinolate sinigrin could be detected at three parts per trillion. This method takes advantage of the glucosinolate anion fragmentation which consistently produces a sulphonate ring-opened glucose moiety in the ion trap mass spectrometer, m/z 259. An intramolecular transfer mechanism for this fragmentation is presented here for the first time. This fragmentation can be exploited as a general identifier of the glucosinolate class of metabolites in plant extracts and in LCMSn can be employed provide positive identification and quantification of individual glucosinolates. Such approaches offer sensitive tools for focused metabolomics analysis and screening of plant breeding lines.

Physiological and clinical consequences of relief of right ventricular outflow tract obstruction late after repair of congenital heart defects.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is a common problem after repair of congenital heart disease. Percutaneous pulmonary valve implantation (PPVI) can treat this condition without consequent pulmonary regurgitation or cardiopulmonary bypass. Our aim was to investigate the clinical and physiological response to relieving RVOTO. METHODS AND RESULTS: We studied 18 patients who underwent PPVI for RVOTO (72% male, median age 20 years) from a total of 93 who had this procedure for various indications. All had a right ventricular outflow tract (RVOT) gradient >50 mm Hg on echocardiography without important pulmonary regurgitation (less than mild or regurgitant fraction <10% on magnetic resonance imaging [MRI]). Cardiopulmonary exercise testing, tissue Doppler echocardiography, and MRI were performed before and within 50 days of PPVI. PPVI reduced RVOT gradient (51.4 to 21.7 mm Hg, P<0.001) and right ventricular systolic pressure (72.8 to 47.3 mm Hg, P<0.001) at catheterization. Symptoms and aerobic (25.7 to 28.9 mL.kg(-1).min(-1), P=0.002) and anaerobic (14.4 to 16.2 mL.kg(-1).min(-1), P=0.002) exercise capacity improved. Myocardial systolic velocity improved acutely (tricuspid 4.8 to 5.3 cm/s, P=0.05; mitral 4.7 to 5.5 cm/s, P=0.01), whereas isovolumic acceleration was unchanged. The tricuspid annular velocity was not maintained on intermediate follow-up. Right ventricular end-diastolic volume (99.9 to 89.7 mL/m2, P<0.001) fell, whereas effective stroke volume (43.7 to 48.3 mL/m2, P=0.06) and ejection fraction (48.0% to 56.8%, P=0.01) increased. Left ventricular end-diastolic volume (72.5 to 77.4 mL/m2, P=0.145), stroke volume (45.3 to 50.6 mL/m2, P=0.02), and ejection fraction (62.6% to 65.8%, P=0.03) increased. CONCLUSIONS: PPVI relieves RVOTO, which leads to an early improvement in biventricular performance. Furthermore, it reduces symptoms and improves exercise tolerance. These findings have important implications for the management of this increasingly common condition.

The isolation and purification of glucoraphanin from broccoli seeds by solid phase extraction and preparative high performance liquid chromatography.

Plant foods contain not only essential nutrients, e.g. protein, amino acids, vitamins and minerals, but also phytochemicals that have added health benefits. One such class of phytochemicals are the glucosinolates. Glucosinolates, particularly glucoraphanin, are predominant in plants of the Brassica genus, most notably in vegetables such as broccoli. There is a growing interest in the role glucoraphanin plays in chemoprotection and as a result there is a requirement to accurately determine the levels of glucoraphanin in vegetable products. Reverse phase ion pair high performance liquid chromatography (HPLC) is the method of choice; however, this work has been hindered by the lack of available standard reference materials. Broccoli seeds, which are particularly rich in glucoraphanin (20-50 mg/g), have proved to be ideal for the isolation of glucoraphanin on the preparative scale. A novel preparative scale HPLC method with simple compound recovery has been developed to meet the need for a glucoraphanin standard.

Characterization of flavonol conjugates in immature leaves of pak choi [Brassica rapa L. Ssp. chinensis L. (Hanelt.)] by HPLC-DAD and LC-MS/MS.

The flavonoid composition of immature leaves of pak choi [Brassica rapa L. ssp. chinensis L. (Hanelt.)] was investigated. Flavonol aglycone content was measured in 11 pak choi varieties, indicating significant differences (P < 0.05) in content between varieties and relatively high contents of kaempferol and isorhamnetin. Levels of quercetin ranged from 3.2 to 6.1 mg/100 g of dry weight (DW), whereas levels of isorhamnetin and kaempferol were significantly higher (8.1-35.1 and 36.0-102.6 mg/100 g of DW, respectively). A large number of glycoside and hydroxycinnamic acid derivatives of quercetin, kaempferol, and isorhamnetin were identified in cv. 'Shanghai' by LC/UV-DAD/ESI-MS/MS. The UV-DAD data allowed identification of hydroxycinnamic acid derivatives, but detailed MS/MS fragmentations were required for the structure elucidation. Pak choi could be a potentially important source of dietary flavonols, in particular, kaempferol and isorhamnetin.