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"Eck, Thomas Van"
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Modeling Energetic Particle Acceleration by Dynamic Small-scale Flux Ropes In the Inner Heliosphere
Interplanetary coronal mass ejections (ICMEs) are major drivers of space weather in the inner heliosphere (which can negatively affect our spacecraft, astronauts, etc.). Traditionally, the scientific community has sought to explain energetic particle acceleration near ICME-driven shocks by invoking diffusive shock acceleration (DSA), which has been well studied. However, recent studies suggest that processes related to magnetic reconnection behind ICME-driven shocks can explain observed flux enhancements that contradict predictions by standard steady state DSA theory. In the previous decade, a combination of DSA at and acceleration by dynamic small-scale flux-ropes (SMFRs) downstream of the shock has been introduced to explain these anomalous flux enhancements. In spite of these recent advances, the study of particle acceleration by SMFRs is relatively new and thus the dominant mechanism through which particles are accelerated by SMFRs is not yet known. Previous in-situ studies of SMFR acceleration of energetic particles in the large-scale solar wind have been limited to acceleration events observed with single spacecraft at or beyond 1 AU, so a new search was conducted using Helios A data with the goal of identifying the first SMFR acceleration event within 1 AU. Two new SMFR acceleration events were revealed by this search. These events were modeled using two complementary approaches: (1) an analytical solution to a Parker transport equation, and (2) a numerical solution to a focused transport equation. The modeling efforts determined that, for the given events: (1) the SMFR acceleration mechanism associated with particle interaction with the component of the SMFR motional electric field parallel to the guide magnetic field dominates particle energy gain in both first and second order Fermi terms for low energies, (2) at higher energies the shear flow and compression acceleration mechanisms compete to accelerate particles, (3) particle escape from the SMFR acceleration plays a key role in reproducing observed spectral slopes, (4) particle energization rates decay at rates of r −1.5 (r refers to the heliocentric radial distance of the observations) or greater for second order Fermi processes, and (5) the Parker assumption (pitch-angle independent distribution function) may not be applicable to all SMFR acceleration events.
Dissertation
The diagnostic accuracy of clinical examination for estimating cardiac index in critically ill patients: the Simple Intensive Care Studies-I
PurposeClinical examination is often the first step to diagnose shock and estimate cardiac index. In the Simple Intensive Care Studies-I, we assessed the association and diagnostic performance of clinical signs for estimation of cardiac index in critically ill patients.MethodsIn this prospective, single-centre cohort study, we included all acutely ill patients admitted to the ICU and expected to stay > 24 h. We conducted a protocolised clinical examination of 19 clinical signs followed by critical care ultrasonography for cardiac index measurement. Clinical signs were associated with cardiac index and a low cardiac index (< 2.2 L min−1 m2) in multivariable analyses. Diagnostic test accuracies were also assessed.ResultsWe included 1075 patients, of whom 783 (73%) had a validated cardiac index measurement. In multivariable regression, respiratory rate, heart rate and rhythm, systolic and diastolic blood pressure, central-to-peripheral temperature difference, and capillary refill time were statistically independently associated with cardiac index, with an overall R2 of 0.30 (98.5% CI 0.25–0.35). A low cardiac index was observed in 280 (36%) patients. Sensitivities and positive and negative predictive values were below 90% for all signs. Specificities above 90% were observed only for 110/280 patients, who had atrial fibrillation, systolic blood pressures < 90 mmHg, altered consciousness, capillary refill times > 4.5 s, or skin mottling over the knee.ConclusionsSeven out of 19 clinical examination findings were independently associated with cardiac index. For estimation of cardiac index, clinical examination was found to be insufficient in multivariable analyses and in diagnostic accuracy tests. Additional measurements such as critical care ultrasonography remain necessary.
Journal Article
Long-term Tumor Control of Benign Intracranial Meningiomas After Radiosurgery in a Series of 4565 Patients
Abstract
BACKGROUND
Radiosurgery is the main alternative to microsurgical resection for benign meningiomas.
OBJECTIVE
To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published.
METHODS
From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.).
RESULTS
Median tumor volume was 4.8 cm3, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up > 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P > .001), for female vs male patients (P > .001), for sporadic vs multiple meningiomas (P > .001), and for skull base vs convexity tumors (P > .001). Permanent morbidity rate was 6.6% at the last follow-up.
CONCLUSION
Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.
Journal Article
Should the ultrasound probe replace your stethoscope? A SICS-I sub-study comparing lung ultrasound and pulmonary auscultation in the critically ill
Background
In critically ill patients, auscultation might be challenging as dorsal lung fields are difficult to reach in supine-positioned patients, and the environment is often noisy. In recent years, clinicians have started to consider lung ultrasound as a useful diagnostic tool for a variety of pulmonary pathologies, including pulmonary edema. The aim of this study was to compare lung ultrasound and pulmonary auscultation for detecting pulmonary edema in critically ill patients.
Methods
This study was a planned sub-study of the Simple Intensive Care Studies-I, a single-center, prospective observational study. All acutely admitted patients who were 18 years and older with an expected ICU stay of at least 24 h were eligible for inclusion. All patients underwent clinical examination combined with lung ultrasound, conducted by researchers not involved in patient care. Clinical examination included auscultation of the bilateral regions for crepitations and rhonchi. Lung ultrasound was conducted according to the Bedside Lung Ultrasound in Emergency protocol. Pulmonary edema was defined as three or more B lines in at least two (bilateral) scan sites. An agreement was described by using the Cohen
κ
coefficient, sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy. Subgroup analysis were performed in patients who were not mechanically ventilated.
Results
The Simple Intensive Care Studies-I cohort included 1075 patients, of whom 926 (86%) were eligible for inclusion in this analysis. Three hundred seven of the 926 patients (33%) fulfilled the criteria for pulmonary edema on lung ultrasound. In 156 (51%) of these patients, auscultation was normal. A total of 302 patients (32%) had audible crepitations or rhonchi upon auscultation. From 130 patients with crepitations, 86 patients (66%) had pulmonary edema on lung ultrasound, and from 209 patients with rhonchi, 96 patients (46%) had pulmonary edema on lung ultrasound. The agreement between auscultation findings and lung ultrasound diagnosis was poor (
κ
statistic 0.25). Subgroup analysis showed that the diagnostic accuracy of auscultation was better in non-ventilated than in ventilated patients.
Conclusion
The agreement between lung ultrasound and auscultation is poor.
Trial registration
NCT02912624
. Registered on September 23, 2016.
Journal Article
Identifying and characterizing high-risk clusters in a heterogeneous ICU population with deep embedded clustering
Critically ill patients constitute a highly heterogeneous population, with seemingly distinct patients having similar outcomes, and patients with the same admission diagnosis having opposite clinical trajectories. We aimed to develop a machine learning methodology that identifies and provides better characterization of patient clusters at high risk of mortality and kidney injury. We analysed prospectively collected data including co-morbidities, clinical examination, and laboratory parameters from a minimally-selected population of 743 patients admitted to the ICU of a Dutch hospital between 2015 and 2017. We compared four clustering methodologies and trained a classifier to predict and validate cluster membership. The contribution of different variables to the predicted cluster membership was assessed using SHapley Additive exPlanations values. We found that deep embedded clustering yielded better results compared to the traditional clustering algorithms. The best cluster configuration was achieved for 6 clusters. All clusters were clinically recognizable, and differed in in-ICU, 30-day, and 90-day mortality, as well as incidence of acute kidney injury. We identified two high mortality risk clusters with at least 60%, 40%, and 30% increased. ICU, 30-day and 90-day mortality, and a low risk cluster with 25–56% lower mortality risk. This machine learning methodology combining deep embedded clustering and variable importance analysis, which we made publicly available, is a possible solution to challenges previously encountered by clustering analyses in heterogeneous patient populations and may help improve the characterization of risk groups in critical care.
Journal Article
Different applications of the KDIGO criteria for AKI lead to different incidences in critically ill patients: a post hoc analysis from the prospective observational SICS-II study
Background
Acute kidney injury (AKI) is a frequent and clinically relevant problem in critically ill patients. Various randomized controlled trials (RCT) have attempted to assess potentially beneficial treatments for AKI. Different approaches to applying the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI make a comparison of studies difficult. The objective of this study was to assess how different approaches may impact estimates of AKI incidence and whether the association between AKI and 90-day mortality varied by the approach used.
Methods
Consecutive acutely admitted adult intensive care patients were included in a prospective observational study. AKI was determined following the KDIGO criteria during the first 7 days of ICU admission. In this post hoc analysis, we assessed whether AKI incidence differed when applying the KDIGO criteria in 30 different possible methods, varying in (A) serum creatinine (sCr), (B) urine output (UO), and (C) the method of combining these two into an outcome, e.g., severe AKI. We assessed point estimates and 95% confidence intervals for each incidence. Univariable regression was used to assess the associations between AKI and 90-day mortality.
Results
A total of 1010 patients were included. Baseline creatinine was available in 449 (44%) patients. The incidence of any AKI ranged from 28% (95%CI 25–31%) to 75% (95%CI 72–77%) depending on the approach used. Methods to estimate missing baseline sCr caused a variation in AKI incidence up to 15%. Different methods of handling UO caused a variation of up to 35%. At 90 days, 263 patients (26%) had died, and all 30 variations were associated with 90-day mortality.
Conclusions
In this cohort of critically ill patients, AKI incidence varied from 28 to 75%, depending on the method used of applying the KDIGO criteria. A tighter adherence to KDIGO definitions is warranted to decrease the heterogeneity of AKI and increase the comparability of future studies.
Journal Article
Non-invasive oscillometric versus invasive arterial blood pressure measurements in critically ill patients: A post hoc analysis of a prospective observational study
The aim was to compare non-invasive blood pressure measurements with invasive blood pressure measurements in critically ill patients.
Non-invasive blood pressure was measured via automated brachial cuff oscillometry, and simultaneously the radial arterial catheter-derived measurement was recorded as part of a prospective observational study. Measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were compared using Bland-Altman and error grid analyses.
Paired measurements of blood pressure were available for 736 patients. Observed mean difference (±SD, 95% limits of agreement) between oscillometrically and invasively measured blood pressure was 0.8 mmHg (±15.7 mmHg, −30.2 to 31.7 mmHg) for SAP, −2.9 mmHg (±11.0 mmHg, −24.5 to 18.6 mmHg) for DAP, and −1.0 mmHg (±10.2 mmHg, −21.0 to 18.9 mmHg) for MAP. Error grid analysis showed that the proportions of measurements in risk zones A to E were 78.3%, 20.7%, 1.0%, 0%, and 0.1% for MAP.
Non-invasive blood pressure measurements using brachial cuff oscillometry showed large limits of agreement compared to invasive measurements in critically ill patients. Error grid analysis showed that measurement differences between oscillometry and the arterial catheter would potentially have triggered at least low-risk treatment decisions in one in five patients.
•Blood pressure measurement methods showed large limits of agreement in critically ill patients•Treatment decisions are potentially different in one in five ICU patients based on blood pressure measurement method used•Blood pressure measurement methods cannot be directly interchanged in critically ill patients
Journal Article
A foundation model for clinical-grade computational pathology and rare cancers detection
The analysis of histopathology images with artificial intelligence aims to enable clinical decision support systems and precision medicine. The success of such applications depends on the ability to model the diverse patterns observed in pathology images. To this end, we present Virchow, the largest foundation model for computational pathology to date. In addition to the evaluation of biomarker prediction and cell identification, we demonstrate that a large foundation model enables pan-cancer detection, achieving 0.95 specimen-level area under the (receiver operating characteristic) curve across nine common and seven rare cancers. Furthermore, we show that with less training data, the pan-cancer detector built on Virchow can achieve similar performance to tissue-specific clinical-grade models in production and outperform them on some rare variants of cancer. Virchow’s performance gains highlight the value of a foundation model and open possibilities for many high-impact applications with limited amounts of labeled training data.
Trained on 1.5 million whole-slide images from 100,000 patients, a pathology foundation model is shown to improve performance of specialized models in detection of rare cancers.
Journal Article
Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature
Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24–233). Median tumour volume was 6.2 cc (+/−7), and the median marginal dose was 14 Gy (+/−3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6–233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.
Journal Article