Ensemble Theory for Force Networks in Hyperstatic Granular Matter

An ensemble approach for force networks in static granular packings is developed. The framework is based on the separation of packing and force scales, together with an a-priori flat measure in the force phase space under the constraints that the contact forces are repulsive and balance on every particle. In this paper we will give a general formulation of this force network ensemble, and derive the general expression for the force distribution $P(f)$. For small regular packings these probability densities are obtained in closed form, while for larger packings we present a systematic numerical analysis. Since technically the problem can be written as a non-invertible matrix problem (where the matrix is determined by the contact geometry), we study what happens if we perturb the packing matrix or replace it by a random matrix. The resulting $P(f)$'s differ significantly from those of normal packings, which touches upon the deep question of how network statistics is related to the underlying network structure. Overall, the ensemble formulation opens up a new perspective on force networks that is analytically accessible, and which may find applications beyond granular matter.Comment: 17 pages, 17 figure

Improving quality of stroke care through benchmarking center performance:why focusing on outcomes is not enough.

Background: Between-center variation in outcome may offer opportunities to identify variation in quality of care. By intervening on these quality differences, patient outcomes may be improved. However, whether observed differences in outcome reflect the true quality improvement potential is not known for many diseases. Therefore, we aimed to analyze the effect of differences in performance on structure and processes of care, and case-mix on between-center differences in outcome after endovascular treatment (EVT) for ischemic stroke. Methods: In this observational cohort study, ischemic stroke patients who received EVT between 2014 and 2017 in all 17 Dutch EVT-centers were included. Primary outcome was the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death), at 90 days. We used random effect proportional odds regression modelling, to analyze the effect of differences in structure indicators (center volume and year of admission), process indicators (time to treatment and use of general anesthesia) and case-mix, by tracking changes in tau2, which represents the amount of between-center variation in outcome. Results: Three thousand two hundred seventy-nine patients were included. Performance on structure and process indicators varied significantly between EVT-centers (P < 0.001). Predicted probability of good functional outcome (modified Rankin Scale 0–2 at 90 days), which can be interpreted as an overall measure of a center’s case-mix, varied significantly between 17 and 50% across centers. The amount of between-center variation (tau2) was estimated at 0.040 in a model only accounting for random variation. This estimate more than doubled after adding case-mix variables (tau2: 0.086) to the model, while a small amount of between-center variation was explained by variation in performance on structure and process indicators (tau2: 0.081 and 0.089, respectively). This indicates that variation in case-mix affects the differences in outcome to a much larger extent. Conclusions: Between-center variation in outcome of ischemic stroke patients mostly reflects differences in case-mix, rather than differences in structure or process of care. Since the latter two capture the real quality improvement potential, these should be used as indicators for comparing center performance. Especially when a strong association exists between those indicators and outcome, as is the case for time to treatment in ischemic stroke

Mechanical Mitral Valve Replacement:A Multicenter Study of Outcomes With Use of 15-to 17-mm Prostheses

Background. The aim of this study was to evaluate early and mid-term outcomes (mortality and prosthetic valve reintervention) after mitral valve replacement with 15- to 17-mm mechanical prostheses. Methods. A multicenter, retrospective cohort study was performed among patients who underwent mitral valve replacement with a 15- to 17-mm mechanical prosthesis at 6 congenital cardiac centers: 5 in The Netherlands and 1 in the United States. Baseline, operative, and follow-up data were evaluated. Results. Mitral valve replacement was performed in 61 infants (15 mm, n = 17 [28%]; 16 mm, n = 18 [29%]; 17 mm, n = 26 [43%]), of whom 27 (47%) were admitted to the intensive care unit before surgery and 22 (39%) required ventilator support. Median age at surgery was 5.9 months (interquartile range [IQR] 3.2-17.4), and median weight was 5.7 kg (IQR, 4.5-8.8). There were 13 in-hospital deaths (21%) and 8 late deaths (17%, among 48 hospital survivors). Major adverse events occurred in 34 (56%). Median follow-up was 4.0 years (IQR, 0.4-12.5) First prosthetic valve replacement (n = 27 [44%]) occurred at a median of 3.7 years (IQR, 1.9-6.8). Prosthetic valve endocarditis was not reported, and there was no mortality related to prosthesis replacement. Other reinterventions included permanent pacemaker implantation (n = 9 [15%]), subaortic stenosis resection (n = 4 [7%]), aortic valve repair (n = 3 [5%], and aortic valve replacement (n = 6 [10%]). Conclusions. Mitral valve replacement with 15- to 17-mm mechanical prostheses is an important alternative to save critically ill neonates and infants in whom the mitral valve cannot be repaired. Prosthesis replacement for outgrowth can be carried out with low risk. (C) 2020 by The Society of Thoracic Surgeons. Published by Elsevier Inc

Fluorescence-Guided Visualization of Soft-Tissue Sarcomas by Targeting Vascular Endothelial Growth Factor A:A Phase 1 Single-Center Clinical Trial

Resection of soft-tissue sarcoma (STS) is accompanied by a high rate of tumor-positive surgical margins (14%-34%), which potentially lead to decreased disease-free survival. Vascular endothelial growth factor A is overexpressed in malignant tumors, including STS, and can be targeted with bevacizumab-800CW during fluorescence-guided surgery for real-time tumor detection. In this phase 1 clinical trial, we determined the feasibility, safety, and optimal dose of bevacizumab-800CW for fluorescence-guided surgery in STS for in vivo and ex vivo tumor detection. Methods: Patients with a histopathologic diagnosis of STS were included. In the dose-escalation phase, patients received bevacizumab-800CW intravenously 3 d before surgery (10, 25, and 50 mg; n = 8). In the subsequent dose-expansion phase, 7 additional patients received bevacizumab800CW at the optimal dose. Fluorescence images were obtained in vivo and ex vivo during all stages of standard care. The optimal dose was determined by calculating in vivo and ex vivo tumor-to-background ratios (TBR) and correlating these results with histopathology. Results: Fifteen patients with STS completed this study. All tumors could be visualized during in vivo and ex vivo imaging. The optimal bevacizumab-800CW dose proved to be 10 mg, with a median in vivo TBR of 2.0 (+/- 0.58) and a median ex vivo TBR of 2.67 (+/- 1.6). All 7 tumor-positive margins could be observed in real time after surgical resection. Conclusion: GS using 10 mg of bevacizumab-800CW is feasible and safe for intraoperative imaging of STS, potentially allowing tumor detection and margin assessment during surgery. An additional follow-up phase 2 study is needed to confirm the diagnostic accuracy

In-vivo Sino-Atrial Node Mapping in Children and Adults With Congenital Heart Disease

BACKGROUND: Sinus node dysfunction (SND) and atrial tachyarrhythmias frequently co-exist in the aging patient with congenital heart disease (CHD), even after surgical correction early in life. We examined differences in electrophysiological properties of the sino-atrial node (SAN) area between pediatric and adult patients with CHD. METHODS: Epicardial mapping of the SAN was performed during sinus rhythm in 12 pediatric (0.6 [0.4–2.4] years) and 15 adult (47 [40–55] years) patients. Unipolar potentials were classified as single-, short or long double- and fractionated potentials. Unipolar voltage, relative R-to-S-amplitude ratio and duration of all potentials was calculated. Conduction velocity (CV) and the amount of conduction block (CB) was calculated. RESULTS: SAN activity in pediatric patients was solely observed near the junction of the superior caval vein and the right atrium, while in adults SAN activity was observed even up to the middle part of the right atrium. Compared to pediatric patients, the SAN region of adults was characterized by lower CV, lower voltages, more CB and a higher degree of fractionation. At the earliest site of activation, single potentials from pediatrics consisted of broad monophasic S-waves with high amplitudes, while adults had smaller rS-potentials with longer duration which were more often fractionated. CONCLUSIONS: Compared to pediatric patients, adults with uncorrected CHD have more inhomogeneous conduction and variations in preferential SAN exit site, which are presumable caused by aging related remodeling. Long-term follow-up of these patients is essential to demonstrate whether these changes are related to development of SND and also atrial tachyarrhythmias early in life

Mechanical Mitral Valve Replacement: A Multicenter Study of Outcomes with Use of 15- to 17-mm Prostheses

Background: The aim of this study was to evaluate early and mid-term outcomes (mortality and prosthetic valve reintervention) after mitral valve replacement with 15- to 17-mm mechanical pr

Hereditary cancer registries improve the care of patients with a genetic predisposition to cancer:contributions from the Dutch Lynch syndrome registry

The Dutch Hereditary Cancer Registry was established in 1985 with the support of the Ministry of Health (VWS). The aims of the registry are: (1) to promote the identification of families with hereditary cancer, (2) to encourage the participation in surveillance programs of individuals at high risk, (3) to ensure the continuity of lifelong surveillance examinations, and (4) to promote research, in particular the improvement of surveillance protocols. During its early days the registry provided assistance with family investigations and the collection of medical data, and recommended surveillance when a family fulfilled specific diagnostic criteria. Since 2000 the registry has focused on family follow-up, and ensuring the quality of surveillance programs and appropriate clinical management. Since its founding, the registry has identified over 10,000 high-risk individuals with a diverse array of hereditary cancer syndromes. All were encouraged to participate in prevention programmes. The registry has published a number of studies that evaluated the outcome of surveillance protocols for colorectal cancer (CRC) in Lynch syndrome, as well as in familial colorectal cancer. In 2006, evaluation of the effect of registration and colonoscopic surveillance on the mortality rate associated with colorectal cancer (CRC) showed that the policy led to a substantial decrease in the mortality rate associated with CRC. Following discovery of MMR gene defects, the first predictive model that could select families for genetic testing was published by the Leiden group. In addition, over the years the registry has produced many cancer risk studies that have helped to develop appropriate surveillance protocols. Hereditary cancer registries in general, and the Lynch syndrome registry in particular, play an important role in improving the clinical management of affected families.</p

Increasing cardio-thoracic productivity at Erasmus MC

The Thoraxcenter of Erasmus MC started an improvement project in 2015 in order to increase the number of open-heart surgeries by 150 for three consecutive years (450 in total, +46%), and to decrease the access time from 12–14 to 2–3 weeks by the end of 2016. This was required to attain economy of scale in a highly competitive market. In this paper we describe the first year of the project, focusing on its structure and interventions taken, resulting in 165 additional open-heart surgeries carried out in 2016 and a significantly shorter access time of 2–3 weeks

Long-Term Cause-Specific Mortality in Hodgkin Lymphoma Patients

BACKGROUND: Few studies have examined the impact of treatment-related morbidity on long-term, cause-specific mortality in Hodgkin lymphoma (HL) patients. METHODS: This multicenter cohort included 4919 HL patients, treated before age 51 years between 1965 and 2000, with a median follow-up of 20.2 years. Standardized mortality ratios, absolute excess mortality (AEM) per 10 000 person-years, and cause-specific cumulative mortality by stage and primary treatment, accounting for competing risks, were calculated. RESULTS: HL patients experienced a 5.1-fold (AEM = 123 excess deaths per 10 000 person-years) higher risk of death due to causes other than HL. This risk remained increased in 40-year survivors (standardized mortality ratio = 5.2, 95% confidence interval [CI] = 4.2 to 6.5, AEM = 619). At age 54 years, HL survivors experienced similar cumulative mortality (20.0%) from causes other than HL to 71-year-old individuals from the general population. Whereas HL mortality statistically significantly decreased over the calendar period (P < .001), solid tumor mortality did not change in the most recent treatment era. Patients treated in 1989-2000 had lower 25-year cardiovascular disease mortality than patients treated in 1965-1976 (4.3% vs 5.7%; subdistribution hazard ratio = 0.65, 95% CI = 0.46 to 0.93). Infectious disease mortality was not only increased after splenectomy but also after spleen irradiation (hazard ratio = 2.81, 95% CI = 1.55 to 5.07). For stage I-II, primary treatment with chemotherapy (CT) alone was associated with statistically significantly higher HL mortality (P < .001 for CT vs radiotherapy [RT]; P = .04 for CT vs RT+CT) but lower 30-year mortality from causes other than HL (15.8%, 95% CI = 9.7% to 23.3%) compared with RT alone (36.9%, 95% CI = 34.0% to 39.8%, P = .001) and RT and CT combined (29.8%, 95% CI = 26.8% to 32.9%, P = .02). CONCLUSIONS: Compared with the general population, HL survivors have a substantially reduced life expectancy. Optimal selection of patients for primary CT is crucial, weighing risks of HL relapse and long-term toxicity