A single-particle characterization of a mobile Versatile Aerosol Concentration Enrichment System for exposure studies

BACKGROUND: An Aerosol Time-of-Flight Mass Spectrometer (ATOFMS) was used to investigate the size and chemical composition of fine concentrated ambient particles (CAPs) in the size range 0.2–2.6 μm produced by a Versatile Aerosol Concentration Enrichment System (VACES) contained within the Mobile Ambient Particle Concentrator Exposure Laboratory (MAPCEL). The data were collected during a study of human exposure to CAPs, in Edinburgh (UK), in February-March 2004. The air flow prior to, and post, concentration in the VACES was sampled in turn into the ATOFMS, which provides simultaneous size and positive and negative mass spectral data on individual fine particles. RESULTS: The particle size distribution was unaltered by the concentrator over the size range 0.2–2.6 μm, with an average enrichment factor during this study of ~5 (after dilution of the final air stream). The mass spectra from single particles were objectively grouped into 20 clusters using the multivariate K-means algorithm and then further grouped manually, according to similarity in composition and time sequence, into 8 main clusters. The particle ensemble was dominated by pure and reacted sea salt and other coarse inorganic dusts (as a consequence of the prevailing maritime-source climatology during the study), with relatively minor contributions from carbonaceous and secondary material. Very minor variations in particle composition were noted pre- and post-particle concentration, but overall there was no evidence of any significant change in particle composition. CONCLUSION: These results confirm, via single particle analysis, the preservation of the size distribution and chemical composition of fine ambient PM in the size range 0.2–2.6 μm after passage through the VACES concentration instrumentation

Are Thiel-embalmed Cadavers Effective Tools in Educating Medical Students to Perform Knee Arthrocentesis?

INTRODUCTION: The purposes of this study are to determine whether Thiel-embalmed cadavers are an effective educational tool in teaching medical students to perform knee arthrocentesis, to compare the use of Thiel-embalmed cadavers to formalin-embalmed cadavers in arthrocentesis education, and to determine whether the use of Thiel-embalmed cadavers is potentially generalizable to the instruction of other orthopedic procedures. METHODS: Sixty-eight third-year medical students participated in the study. The participants first completed a pre-survey to assess their prior experience with arthrocentesis procedures and Thiel-embalmed cadavers. Participants then attended an instructional session where the knee arthrocentesis procedure was demonstrated on a Thiel-embalmed cadaver. Participants then individually performed the simulated knee arthrocentesis procedure twice: once on a Thiel-embalmed cadaver and once on a formalin-embalmed cadaver. Success of each attempt was determined through the visualization of aspirated joint fluid. Following the laboratory session, each participant completed a post-survey to determine whether the session improved their perceived confidence in performing knee arthrocentesis, if they preferred the use of Thiel-embalmed cadavers or formalin-embalmed cadavers as a teaching tool, and if they believed simulated practice using Thiel-embalmed cadavers would be effective for learning other orthopedic procedural skills. RESULTS: Sixty-eight students participated in the laboratory session and successfully completed both pre- and post-course surveys. 96% of participants reported that they felt confident performing knee arthrocentesis under physician supervision following their participation in the laboratory session (versus 15% of participants in the pre-survey). 96% of participants reported that the Thiel-embalmed cadavers provided a more realistic teaching model than formalin-embalmed cadavers for learning knee arthrocentesis. 100% of participants believed the incorporation of simulated practice using Thiel-embalmed cadavers is an effective method in teaching students to perform knee arthrocentesis. 100% of participants reported that they would participate in future sessions using Thiel-embalmed cadavers to learn and practice other orthopedic procedural techniques. DISCUSSION: This study used a moderate sample size of third-year medical students to provide data regarding the suitability of using Thiel cadavers in arthrocentesis education. Results indicate that Thiel cadavers are effective tools in teaching medical students to perform knee arthrocentesis, that students preferred the Thiel cadavers to the formalin cadavers, and that the use of Thiel cadavers is a safe, engaging, and high-quality teaching modality for demonstrating proper arthrocentesis procedural technique to medical students. Since this study looked specifically at teaching knee arthrocentesis to medical students, it is uncertain whether the benefits of Thiel cadavers are generalizable to the education of other orthopedic procedures and subject groups such as residents, fellows, and practicing physicians. Further studies should be performed to assess whether Thiel cadavers are beneficial in teaching other orthopaedic procedures and if these benefits extend to other subject groups

Beneficial cardiovascular effects of reducing exposure to particulate air pollution with a simple facemask

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollution is an important risk factor for cardiovascular morbidity and mortality, and is associated with increased blood pressure, reduced heart rate variability, endothelial dysfunction and myocardial ischaemia. Our objectives were to assess the cardiovascular effects of reducing air pollution exposure by wearing a facemask.</p> <p>Methods</p> <p>In an open-label cross-over randomised controlled trial, 15 healthy volunteers (median age 28 years) walked on a predefined city centre route in Beijing in the presence and absence of a highly efficient facemask. Personal exposure to ambient air pollution and exercise was assessed continuously using portable real-time monitors and global positional system tracking respectively. Cardiovascular effects were assessed by continuous 12-lead electrocardiographic and ambulatory blood pressure monitoring.</p> <p>Results</p> <p>Ambient exposure (PM_2.586 ± 61 <it>vs </it>140 ± 113 μg/m³; particle number 2.4 ± 0.4 <it>vs </it>2.3 ± 0.4 × 10⁴particles/cm³), temperature (29 ± 1 <it>vs </it>28 ± 3°C) and relative humidity (63 ± 10 <it>vs </it>64 ± 19%) were similar (P > 0.05 for all) on both study days. During the 2-hour city walk, systolic blood pressure was lower (114 ± 10 <it>vs </it>121 ± 11 mmHg, P < 0.01) when subjects wore a facemask, although heart rate was similar (91 ± 11 <it>vs </it>88 ± 11/min; P > 0.05). Over the 24-hour period heart rate variability increased (SDNN 65.6 ± 11.5 <it>vs </it>61.2 ± 11.4 ms, P < 0.05; LF-power 919 ± 352 <it>vs </it>816 ± 340 ms², P < 0.05) when subjects wore the facemask.</p> <p>Conclusion</p> <p>Wearing a facemask appears to abrogate the adverse effects of air pollution on blood pressure and heart rate variability. This simple intervention has the potential to protect susceptible individuals and prevent cardiovascular events in cities with high concentrations of ambient air pollution.</p

Inhaled Nanoparticles Accumulate at Sites of Vascular Disease

The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2-200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials

Low serum cortisol predicts early death following acute myocardial infarction

&lt;b&gt;Objective&lt;/b&gt;: Low serum cortisol concentrations have been associated with adverse prognosis in critical illness of diverse aetiology. We aimed to determine whether low serum cortisol concentrations are associated with adverse prognosis in patients with acute myocardial infarction. &lt;b&gt;Design&lt;/b&gt;: Nested case-control study. &lt;b&gt;Setting&lt;/b&gt;: Prospective cohort study of consecutive patients admitted with acute myocardial infarction to 9 Scottish hospitals. &lt;b&gt;Patients&lt;/b&gt;: 100 patients who survived 30 days (controls) and 100 patients who died within 30 days (cases). &lt;b&gt;Measurements and Main Results&lt;/b&gt;: Admission cortisol concentrations were lower in patients who died than those who survived (median 1,189 versus 1,355 nmol/L, p&#60;0.001). A cortisol concentration in the bottom quartile (&#60;1,136 nmol/L) was a strong predictor of death within 30 days, and remained so after adjustment for age and cardiac troponin concentration (adjusted OR 8.78, 95% CI 3.09-24.96, p&#60;0.001). &lt;b&gt;Conclusions&lt;/b&gt;: Patients who mount a lesser cortisol stress response to acute myocardial infarction have a poorer early prognosis

Exposure to concentrated ambient particles does not affect vascular function in patients with coronary heart disease

BACKGROUND: Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans. OBJECTIVES: We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. METHODS: Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables—including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine—6–8 hr after both exposures. RESULTS: Particulate concentrations (mean ± SE) in the exposure chamber (190 ± 37 μg/m(3)) were higher than ambient levels (31 ± 8 μg/m(3)) and levels in filtered air (0.5 ± 0.4 μg/m(3); p < 0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group. CONCLUSIONS: Despite achieving marked increases in particulate matter, exposure to CAPs—low in combustion-derived particles—did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans

Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.

AimsTo examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.Methods and resultsPCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: P P = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (P = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (P = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, P = 0.001) and C-reactive protein (r = 0.41, P P = 0.002). mPCAT density above -74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97-1)]. The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (P = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.ConclusionsPCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780