4 research outputs found
Routing Arena: A Benchmark Suite for Neural Routing Solvers
Neural Combinatorial Optimization has been researched actively in the last
eight years. Even though many of the proposed Machine Learning based approaches
are compared on the same datasets, the evaluation protocol exhibits essential
flaws and the selection of baselines often neglects State-of-the-Art Operations
Research approaches. To improve on both of these shortcomings, we propose the
Routing Arena, a benchmark suite for Routing Problems that provides a seamless
integration of consistent evaluation and the provision of baselines and
benchmarks prevalent in the Machine Learning- and Operations Research field.
The proposed evaluation protocol considers the two most important evaluation
cases for different applications: First, the solution quality for an a priori
fixed time budget and secondly the anytime performance of the respective
methods. By setting the solution trajectory in perspective to a Best Known
Solution and a Base Solver's solutions trajectory, we furthermore propose the
Weighted Relative Average Performance (WRAP), a novel evaluation metric that
quantifies the often claimed runtime efficiency of Neural Routing Solvers. A
comprehensive first experimental evaluation demonstrates that the most recent
Operations Research solvers generate state-of-the-art results in terms of
solution quality and runtime efficiency when it comes to the vehicle routing
problem. Nevertheless, some findings highlight the advantages of neural
approaches and motivate a shift in how neural solvers should be conceptualized
Understanding Selectin Counter-Receptor Binding from Electrostatic Energy Computations and Experimental Binding Studies
Higher
organisms defend themselves against invading micro-organisms and harmful
substances with their immune system. Key players of the immune system
are the white blood cells (WBC), which in case of infection move in
an extravasation process from blood vessels toward infected tissue
promoting inflammation. This process starts with the attachment of
the WBC to the blood vessel wall, mediated by protein pair interactions
of selectins and counter-receptors (C-R). Individual selectin C-R
binding is weak and varies only moderately between the three selectin
types. Multivalency enhances such small differences, rendering selectin-binding
type specific. In this work, we study selectin C-R binding, the initial
step of extravasation. We performed electrostatic energy computations
based on the crystal structure of one selectin type co-crystallized
with the ligating part of the C-R. The agreement with measured free
energies of binding is satisfactory. Additionally, we modeled selectin
mutant structures in order to explain differences in binding of the
different selectin types. To verify our modeling procedures, surface
plasmon resonance data were measured for several mutants and compared
with computed binding affinities. Binding affinities computed with
soaked rather than co-crystallized selectin C-R structures do not
agree with measured data. Hence, these structures are inappropriate
to describe the binding mode. The analysis of selectin/C-R binding
unravels the role played by individual molecular components in the
binding event. This opens new avenues to prevent immune system malfunction,
designing drugs that can control inflammatory processes by moderating
selectin C-R binding
Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.
Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.
Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.
Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.
Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.
Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 and P = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P = .03).
Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.
Trial Registration: Clinicaltrials.gov Identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434