Strand plasticity governs fatigue in colloidal gels

Repeated loading of a solid leads to microstructural damage that ultimately results in catastrophic material failure. While posing a major threat to the stability of virtually all materials, the microscopic origins of fatigue, especially for soft solids, remain elusive. Here we explore fatigue in colloidal gels as prototypical inhomogeneous soft solids by combining experiments and computer simulations. Our results reveal how mechanical loading leads to irreversible strand stretching, which builds slack into the network that softens the solid at small strains and causes strain hardening at larger deformations. We thus find that microscopic plasticity governs fatigue at much larger scales. This gives rise to a new picture of fatigue in soft thermal solids and calls for new theoretical descriptions of soft gel mechanics in which local plasticity is taken into account.Comment: 5 pages, 4 figure

Adjuvant Hepatic Arterial Infusion Pump Chemotherapy After Resection of Colorectal Liver Metastases: Results of a Safety and Feasibility Study in The Netherlands

Background: The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after resection of colorectal liver metastases (CRLMs) was 61% in clinical trials from Memorial Sloan Kettering Cancer Center. A pilot study was performed to evaluate the safety and feasibility of adjuvant HAIP chemotherapy in patients with resectable CRLMs. Study Design: A phase II study was performed in two centers in The Netherlands. Patients with resectable CRLM without extrahepatic disease were eligible. All patients underwent complete resection and/or ablation of CRLMs and pump implantation. Safety was determined by the 90-day HAIP-related postoperative complications from the day of pump placement (Clavien–Dindo classification, grade III or higher) and feasibility by the successful administration of the first cycle of HAIP chemotherapy. Results: A total of 20 patients, with a median age of 57 years (interquartile range [IQR] 51–64) were included. Grade III or higher HAIP-related postoperative complications were found in two patients (10%), both of whom had a reoperation (without laparotomy) to replace a pump with a slow flow rate or to reposition a flipped pump. No arterial bleeding, arterial dissection, arterial thrombosis, extrahepatic perfusion, pump pocket hematoma, or pump pocket infections were found within 90 days after surgery. After a median of 43 days (IQR 29–52) following surgery, all patients received the first dose of HAIP chemotherapy, which was completed un

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial

Background Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. Methods This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4–12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and

Criticality and mechanical enhancement in composite fiber networks

Many biological materials consist of sparse networks of disordered fibers, embedded in a soft elastic matrix. The interplay between rigid and soft elements in such composite networks leads to mechanical properties that can go far beyond the sum of those of the constituents. Here we present lattice-based simulations to unravel the microscopic origins of this mechanical synergy. We show that the competition between fiber stretching and bending and elastic deformations of the matrix gives rise to distinct mechanical regimes, with phase transitions between them that are characterized by critical behavior and diverging strain fluctuations and with different mechanisms leading to mechanical enhancement

Strand Plasticity Governs Fatigue in Colloidal Gels

The repeated loading of a solid leads to microstructural damage that ultimately results in catastrophic material failure. While posing a major threat to the stability of virtually all materials, the microscopic origins of fatigue, especially for soft solids, remain elusive. Here we explore fatigue in colloidal gels as prototypical inhomogeneous soft solids by combining experiments and computer simulations. Our results reveal how mechanical loading leads to irreversible strand stretching, which builds slack into the network that softens the solid at small strains and causes strain hardening at larger deformations. We thus find that microscopic plasticity governs fatigue at much larger scales. This gives rise to a new picture of fatigue in soft thermal solids and calls for new theoretical descriptions of soft gel mechanics in which local plasticity is taken into account.</p

An iterative conditional dispatch algorithm for the dynamic dispatch waves problem

A challenge in same-day delivery operations is that delivery requests are typically not known beforehand, but are instead revealed dynamically during the day. This uncertainty introduces a trade-off between dispatching vehicles to serve requests as soon as they are revealed to ensure timely delivery, and delaying the dispatching decision to consolidate routing decisions with future, currently unknown requests. In this paper we study the dynamic dispatch waves problem, a same-day delivery problem in which vehicles are dispatched at fixed decision moments. At each decision moment, the system operator must decide which of the known requests to dispatch, and how to route these dispatched requests. The operator's goal is to minimize the total routing cost while ensuring all requests are served on time. We propose iterative conditional dispatch (ICD), an iterative solution construction procedure based on a sample scenario approach. ICD iteratively solves sample scenarios to classify requests to be dispatched, postponed, or undecided. The set of undecided requests shrinks in each iteration until a final dispatching decision is made in the last iteration We develop two variants of ICD: one variant based on thresholds, and another variant based on similarity. A significant strength of ICD is that it is conceptually simple and easy to implement. This simplicity does not harm performance: through rigorous numerical experiments, we show that both variants efficiently navigate the large state and action spaces of the dynamic dispatch waves problem and quickly converge to a high-quality solution. In particular, the threshold-based ICD variant improves over a greedy myopic strategy by 27.2% on average, and outperforms methods from the literature by 0.8% on average, and up to 1.5% in several cases