Non-invasive imaging of coronary artery disease and its functional consequences- The Hybrid SPECT and CCTA approach

For several decades invasive coronary angiography (CA) has been the reference standard in the assessment of coronary artery disease (CAD) severity. Patients with high pre-test likelihood of CAD, receive a Class 1 indication for CA. Several factors, however, motivate the need for a reliable non-invasive imaging modality, especially in patients with a high pre-test likelihood. Not only to rule out, but also to reliably diagnose coronary stenosis with functional consequences (significant CAD) and guide therapeutic decision making. Performance of CA in all patients with high pre-test likelihood of CAD has undeniable drawbacks. First of all, the prevalence of angiographically significant CAD in patients with high pre-test likelihood may be as low as 44-46%. In real life, the prevalence of significant CAD in patients referred for CA is even lower at only 36.7%, according to the national cardiovascular data registry of the United States . Secondly, angiographic severity of CAD does not reliably predict its main functional consequence: myocardial ischemia 6-8. Because evidence of myocardial ischemia is needed before deciding whether revascularization is necessary, additional (non- ) invasive tests are needed . Finally, CA comes with high costs as a result of the need for admission to a hospital or day-care facility and a low risk (0.1%) of serious adverse events . With the advent of computed tomography coronary angiography (CCTA) and the known reliability of single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) a combination of non-invasive imaging modalities became available that potentially could reliably diagnose significant CAD. The high diagnostic accuracy of this combination has previously been shown in highly selected patient populations. Nevertheless, data demonstrating the applicability of hybrid SPECT and CCTA in diagnosing significant CAD in stable patients with an intermediate to high pre-test likelihood of CAD are still lacking. Furthermore, the contribution of these tests to therapeutic decision making in these patients is unknown. Providing evidence on both of these issues is the main objective of this thesis

Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells

Background: Previously we found that Rad54/Rad54B cells are more sensitive towards mitomycin C (MMC) as compared to wild-type (WT) cells. This difference in sensitivity was absent upon exposure to other clastogens like bleomycin (BLM) and g-radiation. In order to get further insight into possible underlying mechanisms, gene expression changes in WT and Rad54/Rad54B MEFs (mouse embryonic fibroblasts) after exposure to the clastogens MMC and BLM were investigated. Exposures of these cells to mutagens (N-ac-AAF and ENU) and vehicle were taken as controls. Results: Most exposures resulted in an induction of DNA damage signaling and apoptosis genes and a reduced expression of cell division genes in cells of both genotypes. As expected, responses to N-ac-AAF were very similar in both genotypes. ENU exposure did not lead to significant gene expression changes in cells of both genotypes, presumably due to its short half-life. Gene expression responses to clastogens, however, showed a genotype-dependent effect for BLM and MMC. MMC treated Rad54/Rad54B MEFs showed no induction of p53-signaling, DNA damage response and apoptosis as seen for all the other treatments. Conclusion: These data support our finding that different types of clastogens exist and that responses to these types depend on the DNA repair status of the cells.Toxicogenomics and risk assessmen

Estimating particulate matter health impact related to the combustion of different fossil fuels

International audienceExposure to particulate matter (PM) in ambient air leads to adverse health effects. To design cost effective mitigation strategies, a thorough understanding of the sources of particulate matter is crucial. We have successfully generated a web map service that allows to access information on fuel dependent health effects due to particulate matter. For this purpose, the LOTOS-EUROS air pollution model was equipped with a source apportionment module that tracks the origin of the modelled particulate matter distributions throughout a simulation. Combined with a dedicated emission inventory PM2.5 maps specified by fuel type were generated for 2007-2009. These maps were combined with a health impact calculation to estimate Lost of Life Expectancy for each fuel categories. An user friendly web client was generated to access the results and use the web mapping service in an easy manner

Training self-regulated learning skills with video modeling examples: Do task-selection skills transfer?

Self-assessment and task-selection skills are crucial in self-regulated learning situations in which students can choose their own tasks. Prior research suggested that training with video modeling examples, in which another person (the model) demonstrates and explains the cyclical process of problem-solving task performance, self-assessment, and task-selection, is effective for improving adolescents’ problem-solving posttest performance after self-regulated learning. In these examples, the models used a specific task-selection algorithm in which perceived mental effort and self-assessed performance scores were combined to determine the complexity and support level of the next task, selected from a task database. In the present study we aimed to replicate prior findings and to investigate whether transfer of task-selection skills would be facilitated even more by a more general, heuristic task-selection training than the task-specific algorithm. Transfer of task-selection skills was assessed by having students select a new task in another domain for a fictitious peer student. Results showed that both heuristic and algorithmic training of self-assessment and task-selection skills improved problem-solving posttest performance after a self-regulated learning phase, as well as transfer of task-selection skills. Heurist

Improving Empirical Scrutiny of the Habitus

Many studies invoke the concept of the Bourdieusian habitus to account for a plethora of stratified patterns uncovered by conventional social-scientific methods. However, as a stratumspecific, embodied and largely non-declarative set of dispositions, the role of the habitus in those stratified patterns is typically not adequately scrutinised empirically. Instead, the habitus is often attributed theoretically to an empirically established link between stratification indicators and an outcome of interest. In this research note

Undetectable High-Sensitivity Troponin T as a Gatekeeper for Coronary Computed Tomography Angiography in Patients Suspected of Acute Coronary Syndrome

OBJECTIVES: The aim of this study was to characterize the safety and efficiency of a strategy employing the limit of detection (LoD) of high-sensitivity troponin T (hs-TnT) as a gatekeeper for coronary computed tomography angiography (CCTA) in suspected acute coronary syndrome (ACS) patients in the emergency department (ED). METHODS: We included suspected ACS patients who underwent CCTA and were evaluated with hs-TnT. Patients were categorized as below the LoD and at or above the LoD. The primary outcome was 30-day major adverse cardiac events (MACEs), defined as all-cause mortality, ACS, or coronary revascularization. RESULTS: The study population consisted of 177 patients (mean age 55 ± 10 years, 50.3% women), and 16 (9.0%) patients reached the primary outcome. None of the patients died, while 13 had an adjudicated diagnosis of ACS, and 3 underwent elective coronary revascularization. There were 77 patients (44%) with an hs-TnT value below the LoD (MACEs; n = 1 [1.3%]) and 100 (56%) with at or above the LoD levels (MACEs; n = 15 [15%]). None of 67 patients with an hs-TnT value below the LoD and <50% stenosis on CCTA experienced MACEs. Out of the 10 patients with an hs-TnT value below the LoD and ≥50% stenosis on CCTA, 1 patient underwent elective percutaneous coronary revascularization. In patients with an hs-TnT value at or above the LoD, 74 patients had <50% stenosis on CCTA, and 2 patients (3%) were diagnosed with myocardial infarction without obstructive coronary artery disease confirmed on invasive angiography. Thirteen (50%) patients with an hs-TnT value at or above the LoD and ≥50% stenosis on CCTA experienced MACEs (11 ACS and 2 elective percutaneous coronary revascularizations). CONCLUSION: Our findings support that implementing the LoD of hs-TnT as a gatekeeper may reduce the need for CCTA in suspected ACS patients in the ED

The different risk of new-onset, chronic, worsening, and advanced heart failure:A systematic review and meta-regression analysis

Aims: Heart failure (HF) is a chronic and progressive syndrome associated with a poor prognosis. While it may seem intuitive that the risk of adverse outcomes varies across the different stages of HF, an overview of these risks is lacking. This study aims to determine the risk of all-cause mortality and HF hospitalizations associated with new-onset HF, chronic HF (CHF), worsening HF (WHF), and advanced HF. Methods and results: We performed a systematic review of observational studies from 2012 to 2022 using five different databases. The primary outcomes were 30-day and 1-year all-cause mortality, as well as 1-year HF hospitalization. Studies were pooled using random effects meta-analysis, and mixed-effects meta-regression was used to compare the different HF groups. Among the 15 759 studies screened, 66 were included representing 862 046 HF patients. Pooled 30-day mortality rates did not reveal a significant distinction between hospital-admitted patients, with rates of 10.13% for new-onset HF and 8.11% for WHF (p = 0.10). However, the 1-year mortality risk differed and increased stepwise from CHF to advanced HF, with a rate of 8.47% (95% confidence interval [CI] 7.24–9.89) for CHF, 21.15% (95% CI 17.78–24.95) for new-onset HF, 26.84% (95% CI 23.74–30.19) for WHF, and 29.74% (95% CI 24.15–36.10) for advanced HF. Readmission rates for HF at 1 year followed a similar trend. Conclusions: Our meta-analysis of observational studies confirms the different risk for adverse outcomes across the distinct HF stages. Moreover, it emphasizes the negative prognostic value of WHF as the first progressive stage from CHF towards advanced HF.</p

Round-the-clock performance of coronary CT angiography for suspected acute coronary syndrome: Results from the BEACON trial

Objective: To assess the image quality of coronary CT angiography (CCTA) for suspected acute coronary syndrome (ACS) outside office hours. Methods: Patients with symptoms suggestive of an ACS underwent CCTA at the emergency department 24 hours, 7 days a week. A total of 118 patients, of whom 89 (75 %) presented during office hours (weekdays between 07:00 and 17:00) and 29 (25 %) outside office hours (weekdays between 17:00 and 07:00, weekends and holidays) underwent CCTA. Image quality was evaluated per coronary segment by two experienced readers and graded on an ordinal scale ranging from 1 to 3. Results: There were no significant differences in acquisition parameters, beta-blocker administration or heart rate between patients presenting during office hours and outside office hours. The median quality score per patient was 30.5 [interquartile range 26.0–33.5] for patients presenting during office hours in comparison to 27.5 [19.75–32.0] for patients presenting outside office hours (p=0.043). The number of non-evaluable segments was lower for patients presenting during office hours (0 [0–1.0] vs. 1.0 [0–4.0], p=0.009). Conclusion: Image quality of CCTA outside office hours in the diagnosis of suspected ACS is diminished. Key Points: • Quality scores were higher for coronary-CTA during office hours.• There were no differences in acquisition parameters.• There was a non-significant trend towards higher heart rates outside office hours.• Coronary-CTA on the ED requires state-of-the-art scanner technology and sufficiently trained staff.• Coronary-CTA on the ED needs preparation time and optimisation o

Curriculum vitae of the LOTOS-EUROS (v2.0) chemistry transport model

The development and application of chemistry transport models has a long tradition. Within the Netherlands the LOTOS–EUROS model has been developed by a consortium of institutes, after combining its independently developed predecessors in 2005. Recently, version 2.0 of the model was released as an open-source version. This paper presents the curriculum vitae of the model system, describing the model's history, model philosophy, basic features and a validation with EMEP stations for the new benchmark year 2012, and presents cases with the model's most recent and key developments. By setting the model developments in context and providing an outlook for directions for further development, the paper goes beyond the common model description. With an origin in ozone and sulfur modelling for the models LOTOS and EUROS, the application areas were gradually extended with persistent organic pollutants, reactive nitrogen, and primary and secondary particulate matter. After the combination of the models to LOTOS–EUROS in 2005, the model was further developed to include new source parametrizations (e.g. road resuspension, desert dust, wildfires), applied for operational smog forecasts in the Netherlands and Europe, and has been used for emission scenarios, source apportionment, and long-term hindcast and climate change scenarios. LOTOS–EUROS has been a front-runner in data assimilation of ground-based and satellite observations and has participated in many model intercomparison studies. The model is no longer confined to applications over Europe but is also applied to other regions of the world, e.g. China. The increasing interaction with emission experts has also contributed to the improvement of the model's performance. The philosophy for model development has always been to use knowledge that is state of the art and proven, to keep a good balance in the level of detail of process description and accuracy of input and output, and to keep a good record on the effect of model changes using benchmarking and validation. The performance of v2.0 with respect to EMEP observations is good, with spatial correlations around 0.8 or higher for concentrations and wet deposition. Temporal correlations are around 0.5 or higher. Recent innovative applications include source apportionment and data assimilation, particle number modelling, and energy transition scenarios including corresponding land use changes as well as Saharan dust forecasting. Future developments would enable more flexibility with respect to model horizontal and vertical resolution and further detailing of model input data. This includes the use of different sources of land use characterization (roughness length and vegetation), detailing of emissions in space and time, and efficient coupling to meteorology from different meteorological models